<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03256344</url>
  </required_header>
  <id_info>
    <org_study_id>20140299</org_study_id>
    <nct_id>NCT03256344</nct_id>
  </id_info>
  <brief_title>Study of Talimogene Laherparepvec With Atezolizumab for Triple Negative Breast Cancer and Colorectal Cancer With Liver Metastases</brief_title>
  <official_title>A Phase 1b Study of Talimogene Laherparepvec in Combination With Atezolizumab in Subjects With Triple Negative Breast Cancer and Colorectal Cancer With Liver Metastases</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Amgen</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Roche-Genentech</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Amgen</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Approximately 36 DLT-evaluable subjects will be enrolled in this study. The locations of the&#xD;
      study will be in the United States, Australia, Europe and Switzerland.&#xD;
&#xD;
      The goal of this study is to evaluate the safety of intrahepatic injection (directly into the&#xD;
      liver) of talimogene laherparepvec in combination with intravenously administered&#xD;
      atezolizumab in subjects with triple negative breast cancer and colorectal cancer with liver&#xD;
      metastases.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The Screening period is 28 days prior to study enrollment. This study has 2 Cohorts. Cohort&#xD;
      1: Triple Negative Breast Cancer and Cohort 2: Colorectal Cancer. These cohorts will enroll&#xD;
      in parallel. There will be a Safety Follow-up period and a Long Term Follow-up period.&#xD;
&#xD;
      Drug Administration: The participants will receive the study drugs in cycles. If the&#xD;
      participants are found to be eligible to take part in this study, they will receive&#xD;
      talimogene laherparepvec as an injection into the hepatic (liver) metastatic sites on Day 1&#xD;
      of each cycle along with receiving atezolizumab by intravenous infusion on Day 1 of each&#xD;
      cycle. Each cycle is 21 days for 6 cycles. There is an option for an additional 6 cycles&#xD;
      after the first 6 intra-hepatic cycles. After the first radiographic assessment at week 10,&#xD;
      if all injectable liver lesions have been injected but the 4.0 mL maximum volume has not been&#xD;
      used, injection of clinically assessed non-hepatic cutaneous, subcutaneous, and nodal tumor&#xD;
      lesions with or without ultrasound guidance will be permitted. Liver lesions should be&#xD;
      prioritized over cutaneous, subcutaneous and nodal lesions.&#xD;
&#xD;
      Treatment will continue until a participant experiences a DLT (Dose Limiting Toxicity)&#xD;
      evaluated in the DLT period (which is 2 cycles from initial dose), has CR (Complete&#xD;
      Response), has need for an alternative anticancer therapy or experiences a safety concern.&#xD;
&#xD;
      Study Visits: Cycle 1 to Cycle 12 - The participant will have a physical exam along with&#xD;
      vital signs and ECOG (Eastern Cooperative Oncology Group) performance level assessment. Blood&#xD;
      (about 2 Tablespoons) will be drawn for routine tests and to check the immune system. Adverse&#xD;
      events and medications taken will be reviewed on each cycle.Biomarkers will be taken on&#xD;
      cycles 1, 2, 3, 6, and safety FU. Tumor Markers (special lab tests associated with the&#xD;
      cancer, such as particular proteins) will be completed will be take on cycles 1, 4, 7, 10,&#xD;
      13, every 3 cycles and SFU.&#xD;
&#xD;
      Central lab tests will be completed on cycles 1, 2, 3, and 6 and safety FU. Cycle 1 Archived&#xD;
      (prior stored) tumor sample will be obtained. Also, a liver tumor biopsy will be completed at&#xD;
      Cycles 1, 3 and 6.&#xD;
&#xD;
      Response Assessments will be completed at Screening and again at Cycles 4, 7, 10, 13 and&#xD;
      every 3 cycles.&#xD;
&#xD;
      Throughout the trial a swab for Herpetic tumor will be obtained within 3 days of the event.&#xD;
&#xD;
      Cycle 1 to 12- The exposure to talimogene laherparepvec by the subject's healthcare provider&#xD;
      and household member caregiver will be reviewed. Cycles 1, 3, 6-Liver tumor biopsy will be&#xD;
      completed. Cycles 4, 7, 10, 13 and every 3 cycles -Response assessments will be completed by&#xD;
      radiographic and clinical tumor assessment.&#xD;
&#xD;
      Length of Treatment:&#xD;
&#xD;
      A maximum for 12 cycles of talimogene laherparepvec are allowed during the study. The&#xD;
      participant may continue taking the study drug for as long as the doctor thinks it is in&#xD;
      their best interest. The participant will no longer be able to take the study drug if the&#xD;
      disease gets worse, or if they are unable to follow study directions.&#xD;
&#xD;
      Safety Follow-up Visit:&#xD;
&#xD;
      Safety Follow-up visit will be performed about 30 days after the last dose of study&#xD;
      treatment.&#xD;
&#xD;
      The participant will have a physical exam, have vital signs taken, assessment of ECOG status&#xD;
      and have weight measured. Adverse events will be assessed as well as the concominant&#xD;
      medications. Routine bloodwork and tumor markers will be taken.&#xD;
&#xD;
      Exposure to talimogene laherparepvec by the healthcare providers of the participant and/or&#xD;
      close contacts will be assessed.&#xD;
&#xD;
      Long-Term Follow-up Visits: Participants will be followed for survival every 12 weeks from&#xD;
      the date of the safety follow-up visit until approximately 24 months after the last subject&#xD;
      is enrolled. Subsequent cancer treatments will be collected as part of the long-term&#xD;
      follow-up survival assessment. This is an investigational study. The study doctor can explain&#xD;
      how the study drugs are designed to work.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">March 19, 2018</start_date>
  <completion_date type="Actual">December 3, 2021</completion_date>
  <primary_completion_date type="Actual">May 26, 2020</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Other</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Participants Who Experienced a Dose-Limiting Toxicity (DLT)</measure>
    <time_frame>From Day 1 up to the start of Cycle 3 (each cycle is 21 days)</time_frame>
    <description>Toxicities were graded using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. A DLT was considered as any of the below, if judged by the investigator to be related to either treatment:&#xD;
Grade ≥ 4 neutropenia (absolute neutrophil count [ANC] &lt; 500/μl) lasting ≥ 7 days&#xD;
Grade ≥ 3 febrile neutropenia&#xD;
Grade ≥ 4 thrombocytopenia&#xD;
Grade ≥ 4 anemia&#xD;
Grade ≥ 4 rash&#xD;
Serious herpetic events&#xD;
Grade ≥ 3 symptomatic hepatic toxicities that do not resolve to Grade ≤ 2 within 48 hours or Grade ≥ 3 asymptomatic hepatic toxicities that do not resolve to Grade ≤ 1 within 3 weeks of onset&#xD;
Grade ≥ 3 non-hematologic, non-hepatic organ toxicity&#xD;
Grade 5 toxicity (ie, death)&#xD;
Any other intolerable toxicity leading to permanent discontinuation of treatment&#xD;
DLTs were to occur within the DLT evaluation period, defined as the period between the initial 10^6 PFU/mL dose and 3 weeks following the initial 10^8 PFU/mL dose or the start of Cycle 3, whichever occurred first.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Objective Response Rate (ORR)</measure>
    <time_frame>Every 12 weeks (± 28 days) up to approximately 3.5 years.</time_frame>
    <description>ORR was defined as the incidence rate of either a complete response (CR) or partial response (PR) based on modified immune-related response criteria simulating Response Evaluation Criteria in Solid Tumors(irRC-RECIST) criteria. A CR was a complete disappearance of all lesions and a PR was a decrease in tumor burden 30% or more relative to baseline.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Best Overall Response (BOR)</measure>
    <time_frame>Every 12 weeks (± 28 days) up to approximately 3.5 years.</time_frame>
    <description>BOR was defined as the best visit response based on modified irRC-RECIST criteria:&#xD;
CR: a complete disappearance of all lesions&#xD;
PR: a decrease in tumor burden 30% or more relative to baseline&#xD;
Stable disease (SD): neither sufficient shrinkage to qualify for CR or PR nor sufficient increase to qualify for progressive disease (PD)&#xD;
PD: an increase in tumor burden of 20% or more and at least 5 mm absolute increase relative to nadir (minimum recorded tumor burden)&#xD;
Unevaluable (UE): any lesion present at baseline which was not assessed or was unable to be evaluated leading to an inability to determine the status of that particular tumor</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Response (DOR)</measure>
    <time_frame>Every 12 weeks (± 28 days) up to approximately 3.5 years.</time_frame>
    <description>DOR was defined as the time from the date of an initial response that is subsequently confirmed to the earlier of PD per modified irRC RECIST or death. Participants who have not ended their response at the time of analysis were censored at the last evaluable tumor assessment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Lesion Level Response in Injected Tumor Lesions</measure>
    <time_frame>Every 12 weeks (± 28 days) up to approximately 3.5 years.</time_frame>
    <description>Responses for individual tumor lesions for hepatic and non-hepatic tumors injected wtih treatment were assessed for the following responses:&#xD;
Lesion complete response rate (L-CRR): Disappearance of lesion&#xD;
Lesion partial response rate (L-PRR): Decrease in tumor burden 30% or more relative to baseline&#xD;
Lesion objective response rate (L-ORR): Either a L-CRR or L-PRR based on modified irRC-RECIST criteria</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Lesion Level Response in Uninjected Tumor Lesions</measure>
    <time_frame>Every 12 weeks (± 28 days) up to approximately 3.5 years.</time_frame>
    <description>Responses for individual tumor lesions for hepatic and non-hepatic tumors that were not injected with treatment were assessed for the following responses:&#xD;
L-CRR: Disappearance of lesion&#xD;
L-PRR: Decrease in tumor burden 30% or more relative to baseline&#xD;
L-ORR: Either a L-CRR or L-PRR based on modified irRC-RECIST criteria</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Durable Response Rate (DRR)</measure>
    <time_frame>Every 12 weeks (± 28 days) up to approximately 3.5 years.</time_frame>
    <description>DRR was defined as the percentage of participants with an objective response with a DOR of at least 6 months.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease Control Rate (DCR)</measure>
    <time_frame>Every 12 weeks (± 28 days) up to approximately 3.5 years.</time_frame>
    <description>DCR was defined as the percentage of participants that have a best overall response in one of the following categories: CR/PR/SD.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-free Survival (PFS)</measure>
    <time_frame>Every 12 weeks (± 28 days) up to approximately 3.5 years.</time_frame>
    <description>PFS was defined as time from first dose to the date of first of confirmed disease progression per modified irRC-RECIST criteria, or death (whichever occurred first). Results were estimated using the Kaplan-Meier method.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival (OS)</measure>
    <time_frame>Every 12 weeks (± 28 days) up to approximately 3.5 years.</time_frame>
    <description>OS was defined as the time from the date of first dose to the date of death from any cause. Results were estimated using the Kaplan-Meier method.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">36</enrollment>
  <condition>Metastatic Triple Negative Breast Cancer</condition>
  <condition>Metastatic Colorectal Cancer</condition>
  <arm_group>
    <arm_group_label>Talimogene Laherparepvec with Atezolizumab: Triple Negative Breast Cancer (TNBC)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants with TNBC with liver metastases administered intrahepatic injection of talimogene laherparepvec into liver metastases via guided injection (either ultrasound or computerized tomography) on Day 1 of each cycle for a maximum of 12 cycles, where each cycle is 21 days. Participants administered 10^6 plaque-forming units/milliliter (PFU/mL) on Day 1 of Cycle 1 and 10^8 PFU/mL on Day 1 of each cycle thereafter. Participants also administered 1200 mg atezolizumab via intravenous injection on Day 1 of each cycle.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Talimogene Laherparepvec with Atezolizumab: Colorectal Cancer (CRC)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants with CRC with liver metastases administered intrahepatic injection of talimogene laherparepvec into liver metastases via guided injection (either ultrasound or computerized tomography) on Day 1 of each cycle for a maximum of 12 cycles, where each cycle is 21 days. Participants administered 10^6 PFU/mL on Day 1 of Cycle 1 and 10^8 PFU/mL on Day 1 of each cycle thereafter. Participants also administered 1200 mg atezolizumab via intravenous injection on Day 1 of each cycle.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Talimogene Laherparepvec</intervention_name>
    <description>Virally based anti-cancer immunotherapy given by direct injection into tumors.</description>
    <arm_group_label>Talimogene Laherparepvec with Atezolizumab: Colorectal Cancer (CRC)</arm_group_label>
    <arm_group_label>Talimogene Laherparepvec with Atezolizumab: Triple Negative Breast Cancer (TNBC)</arm_group_label>
    <other_name>IMLYGIC</other_name>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Atezolizumab</intervention_name>
    <description>A monoclonal antibody given by intravenous injection.</description>
    <arm_group_label>Talimogene Laherparepvec with Atezolizumab: Colorectal Cancer (CRC)</arm_group_label>
    <arm_group_label>Talimogene Laherparepvec with Atezolizumab: Triple Negative Breast Cancer (TNBC)</arm_group_label>
    <other_name>MPDL3280A</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Criteria1, Participant provided informed consent prior to any study-specific&#xD;
             activities/procedures.&#xD;
&#xD;
          -  Criteria 2, Confirmation of triple negative breast cancer or colorectal cancer with&#xD;
             liver metastases by laboratory testing.&#xD;
&#xD;
          -  Criteria 3, Subjects with triple negative breast cancer with liver metastases, or&#xD;
             subjects with colorectal cancer with liver metastases are eligible if they have had&#xD;
             disease progression during or after one or more prior standard of care systemic&#xD;
             anti-cancer therapy (eg,chemotherapy, targeted therapy) for metastatic disease or if&#xD;
             they progress during or within 6 months of receiving adjuvant therapy. If subjects, in&#xD;
             the opinion of the investigator, are deemed not appropriate candidates for systemic&#xD;
             anti-cancer therapy for metastatic disease or if they refuse systemic anti-cancer&#xD;
             therapy for metastatic disease, they may be eligible after investigator discussion&#xD;
             with Sponsor medical monitor for approval.&#xD;
&#xD;
          -  Criteria 4, Participants have measurable disease which is equal to one or more&#xD;
             metastatic liver lesions that can be accurately and serially measured that are greater&#xD;
             than or equal to 1 cm dimension and for which the longest diameter is greater or equal&#xD;
             to 1 cm as measured by CT (Computed Tomography) scan or magnetic resonance imaging.&#xD;
             The metastatic liver lesion(s) must not be in an area that received prior localized&#xD;
             therapies.&#xD;
&#xD;
          -  Criteria 5, Metastatic liver lesions for injection must be without necrosis (dead&#xD;
             tissue )and must be be located where any tumor swelling will not lead to gall bladder&#xD;
             tract obstruction or lead to bleeding risk.&#xD;
&#xD;
          -  Criteria 6, Eastern Cooperative Oncology Group performance status (ECOG PS) 0 or 1.&#xD;
&#xD;
          -  Criteria 7, Life expectancy greater than or equal to 5 months.&#xD;
&#xD;
          -  Criteria 8, Adequate organ function within 4 weeks prior to enrollment. This includes&#xD;
             hematology, renal, hepatic and blood-clotting functions as defined by protocol.&#xD;
&#xD;
          -  Criteria 9, Female subjects of childbearing potential should have a negative serum&#xD;
             pregnancy test within 1 week prior to enrollment.&#xD;
&#xD;
          -  Criteria 10, Other Inclusion Criteria May Apply.&#xD;
&#xD;
        Exclusion criteria:&#xD;
&#xD;
          -  Criteria 1, Participant is a candidate for hepatic surgery or local regional therapy&#xD;
             of liver metastases with curative intent.&#xD;
&#xD;
          -  Criteria 2, More than one third of the liver is estimated to be involved with&#xD;
             metastases.&#xD;
&#xD;
          -  Criteria 3, There is invasion by cancer into the main blood vessels such as the portal&#xD;
             vein, hepatic vein or the vena cava.&#xD;
&#xD;
          -  Criteria 4, Participant is currently receiving or has received liver&#xD;
             metastatic-directed therapy ( eg: radiation, ablation, embolization) less than 4 wks&#xD;
             prior to enrollment or hepatic surgery.&#xD;
&#xD;
          -  Criteria 5, History of other malignancy within the past 5 years prior to enrollment&#xD;
             with some exceptions, as outlined in the protocol.&#xD;
&#xD;
          -  Criteria 6, Active or untreated central nervous system (CNS) metastases per CT or&#xD;
             magnetic resonance imagine (MRI) evaluation during screening.&#xD;
&#xD;
          -  Participants with a history of CNS metastases are eligible provided they are stable&#xD;
             and meet the criteria details in the protocol.&#xD;
&#xD;
          -  Criteria 7, Other Medical Conditions as noted in the protocol.&#xD;
&#xD;
          -  Criteria 8, Other Exclusion Criteria May Apply.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>99 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>MD</last_name>
    <role>Study Director</role>
    <affiliation>Amgen</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of California Los Angeles</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90095</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Columbia University Medical Center</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10032</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Stony Brook University</name>
      <address>
        <city>Stony Brook</city>
        <state>New York</state>
        <zip>11794-9446</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Liverpool Hospital</name>
      <address>
        <city>Liverpool</city>
        <state>New South Wales</state>
        <zip>2170</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Monash Medical Centre</name>
      <address>
        <city>Clayton</city>
        <state>Victoria</state>
        <zip>3168</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fiona Stanley Hospital</name>
      <address>
        <city>Murdoch</city>
        <state>Western Australia</state>
        <zip>6150</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Breast Cancer Research Centre - WA</name>
      <address>
        <city>Nedlands</city>
        <state>Western Australia</state>
        <zip>6009</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universite Catholique de Louvain Cliniques Universitaires Saint Luc</name>
      <address>
        <city>Bruxelles</city>
        <zip>1200</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitair Ziekenhuis Gent</name>
      <address>
        <city>Gent</city>
        <zip>9000</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Charite UniversitÃ¤tsmedizin Berlin, CharitÃ© Campus Virchow-Klinikum</name>
      <address>
        <city>Berlin</city>
        <zip>13353</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UniversitÃ¤tsklinikum Bonn</name>
      <address>
        <city>Bonn</city>
        <zip>53105</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UniversitÃ¤tsklinik TÃ¼bingen</name>
      <address>
        <city>TÃ¼bingen</city>
        <zip>72076</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital del Mar</name>
      <address>
        <city>Barcelona</city>
        <state>CataluÃ±a</state>
        <zip>08003</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital General Universitario Gregorio MaraÃ±on</name>
      <address>
        <city>Madrid</city>
        <zip>28007</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Ramon y Cajal</name>
      <address>
        <city>Madrid</city>
        <zip>28034</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Inselspital Bern</name>
      <address>
        <city>Bern</city>
        <zip>3010</zip>
        <country>Switzerland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hopitaux Universitaires de Geneve</name>
      <address>
        <city>Geneva 14</city>
        <zip>1211</zip>
        <country>Switzerland</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Australia</country>
    <country>Belgium</country>
    <country>Germany</country>
    <country>Spain</country>
    <country>Switzerland</country>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://www.amgentrials.com</url>
    <description>AmgenTrials clinical trials website</description>
  </link>
  <verification_date>November 2022</verification_date>
  <study_first_submitted>August 8, 2017</study_first_submitted>
  <study_first_submitted_qc>August 17, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 22, 2017</study_first_posted>
  <results_first_submitted>May 13, 2021</results_first_submitted>
  <results_first_submitted_qc>May 13, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">June 9, 2021</results_first_posted>
  <last_update_submitted>November 22, 2022</last_update_submitted>
  <last_update_submitted_qc>November 22, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">November 25, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Liver Metastases</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Breast Neoplasms</mesh_term>
    <mesh_term>Colorectal Neoplasms</mesh_term>
    <mesh_term>Neoplasm Metastasis</mesh_term>
    <mesh_term>Triple Negative Breast Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Atezolizumab</mesh_term>
    <mesh_term>Talimogene laherparepvec</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
    <ipd_time_frame>Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.</ipd_time_frame>
    <ipd_access_criteria>Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors. If not approved, a Data Sharing Independent Review Panel will arbitrate and make the final decision. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below.</ipd_access_criteria>
    <ipd_url>https://www.amgen.com/datasharing</ipd_url>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>July 8, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/44/NCT03256344/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>November 25, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/44/NCT03256344/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Participants were enrolled at 15 research centers in Australia, Belgium, Germany, Spain, Switzerland and the United States.</recruitment_details>
      <pre_assignment_details>Participants were enrolled between 19 March 2018 and 03 December 2021. A total of 11 subjects with triple negative breast cancer were enrolled and 25 subjects with colorectal cancer.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Talimogene Laherparepvec With Atezolizumab: Triple Negative Breast Cancer (TNBC)</title>
          <description>Participants with TNBC with liver metastases were administered intrahepatic injection of talimogene laherparepvec into liver metastases via guided injection (either ultrasound or computerized tomography) on Day 1 of each cycle for a maximum of 12 cycles, where each cycle was 21 days. Participants were administered 10^6 plaque-forming units/milliliter (PFU/mL) on Day 1 of Cycle 1 and 10^8 PFU/mL on Day 1 of each cycle thereafter. Participants were also administered 1200 mg atezolizumab via intravenous injection on Day 1 of each cycle.</description>
        </group>
        <group group_id="P2">
          <title>Talimogene Laherparepvec With Atezolizumab: Colorectal Cancer (CRC)</title>
          <description>Participants with CRC with liver metastases were administered intrahepatic injection of talimogene laherparepvec into liver metastases via guided injection (either ultrasound or computerized tomography) on Day 1 of each cycle for a maximum of 12 cycles, where each cycle was 21 days. Participants were administered 10^6 PFU/mL on Day 1 of Cycle 1 and 10^8 PFU/mL on Day 1 of each cycle thereafter. Participants were also administered 1200 mg atezolizumab via intravenous injection on Day 1 of each cycle.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="11"/>
                <participants group_id="P2" count="25"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Received Talimogene Laherparepvec</title>
              <participants_list>
                <participants group_id="P1" count="8"/>
                <participants group_id="P2" count="23"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Received Atezolizumab</title>
              <participants_list>
                <participants group_id="P1" count="10"/>
                <participants group_id="P2" count="24"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Safety Analysis Set</title>
              <participants_list>
                <participants group_id="P1" count="10"/>
                <participants group_id="P2" count="24"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="10"/>
                <participants group_id="P2" count="25"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Death</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="22"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="3"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Sponsor Decision</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>All enrolled participants.</population>
      <group_list>
        <group group_id="B1">
          <title>Talimogene Laherparepvec With Atezolizumab: Triple Negative Breast Cancer (TNBC)</title>
          <description>Participants with TNBC with liver metastases were administered intrahepatic injection of talimogene laherparepvec into liver metastases via guided injection (either ultrasound or computerized tomography) on Day 1 of each cycle for a maximum of 12 cycles, where each cycle was 21 days. Participants were administered 10^6 plaque-forming units/milliliter (PFU/mL) on Day 1 of Cycle 1 and 10^8 PFU/mL on Day 1 of each cycle thereafter. Participants were also administered 1200 mg atezolizumab via intravenous injection on Day 1 of each cycle.</description>
        </group>
        <group group_id="B2">
          <title>Talimogene Laherparepvec With Atezolizumab: Colorectal Cancer (CRC)</title>
          <description>Participants with CRC with liver metastases were administered intrahepatic injection of talimogene laherparepvec into liver metastases via guided injection (either ultrasound or computerized tomography) on Day 1 of each cycle for a maximum of 12 cycles, where each cycle was 21 days. Participants were administered 10^6 PFU/mL on Day 1 of Cycle 1 and 10^8 PFU/mL on Day 1 of each cycle thereafter. Participants were also administered 1200 mg atezolizumab via intravenous injection on Day 1 of each cycle.</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="11"/>
            <count group_id="B2" value="25"/>
            <count group_id="B3" value="36"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                    <measurement group_id="B2" value="15"/>
                    <measurement group_id="B3" value="25"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="11"/>
                    <measurement group_id="B2" value="12"/>
                    <measurement group_id="B3" value="23"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="13"/>
                    <measurement group_id="B3" value="13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="11"/>
                    <measurement group_id="B2" value="24"/>
                    <measurement group_id="B3" value="35"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                    <measurement group_id="B2" value="22"/>
                    <measurement group_id="B3" value="32"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants Who Experienced a Dose-Limiting Toxicity (DLT)</title>
        <description>Toxicities were graded using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. A DLT was considered as any of the below, if judged by the investigator to be related to either treatment:&#xD;
Grade ≥ 4 neutropenia (absolute neutrophil count [ANC] &lt; 500/μl) lasting ≥ 7 days&#xD;
Grade ≥ 3 febrile neutropenia&#xD;
Grade ≥ 4 thrombocytopenia&#xD;
Grade ≥ 4 anemia&#xD;
Grade ≥ 4 rash&#xD;
Serious herpetic events&#xD;
Grade ≥ 3 symptomatic hepatic toxicities that do not resolve to Grade ≤ 2 within 48 hours or Grade ≥ 3 asymptomatic hepatic toxicities that do not resolve to Grade ≤ 1 within 3 weeks of onset&#xD;
Grade ≥ 3 non-hematologic, non-hepatic organ toxicity&#xD;
Grade 5 toxicity (ie, death)&#xD;
Any other intolerable toxicity leading to permanent discontinuation of treatment&#xD;
DLTs were to occur within the DLT evaluation period, defined as the period between the initial 10^6 PFU/mL dose and 3 weeks following the initial 10^8 PFU/mL dose or the start of Cycle 3, whichever occurred first.</description>
        <time_frame>From Day 1 up to the start of Cycle 3 (each cycle is 21 days)</time_frame>
        <population>DLT Analysis Set: All participants who had opportunity to receive treatment for 2 cycles from the time of initial dose of study treatment and who had received 2 doses of talimogene laherparepvec and 2 doses of atezolizumab in combination or had a DLT during the DLT-evaluation period.</population>
        <group_list>
          <group group_id="O1">
            <title>Talimogene Laherparepvec With Atezolizumab: Triple Negative Breast Cancer (TNBC)</title>
            <description>Participants with TNBC with liver metastases were administered intrahepatic injection of talimogene laherparepvec into liver metastases via guided injection (either ultrasound or computerized tomography) on Day 1 of each cycle for a maximum of 12 cycles, where each cycle was 21 days. Participants were administered 10^6 plaque-forming units/milliliter (PFU/mL) on Day 1 of Cycle 1 and 10^8 PFU/mL on Day 1 of each cycle thereafter. Participants were also administered 1200 mg atezolizumab via intravenous injection on Day 1 of each cycle.</description>
          </group>
          <group group_id="O2">
            <title>Talimogene Laherparepvec With Atezolizumab: Colorectal Cancer (CRC)</title>
            <description>Participants with CRC with liver metastases were administered intrahepatic injection of talimogene laherparepvec into liver metastases via guided injection (either ultrasound or computerized tomography) on Day 1 of each cycle for a maximum of 12 cycles, where each cycle was 21 days. Participants were administered 10^6 PFU/mL on Day 1 of Cycle 1 and 10^8 PFU/mL on Day 1 of each cycle thereafter. Participants were also administered 1200 mg atezolizumab via intravenous injection on Day 1 of each cycle.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants Who Experienced a Dose-Limiting Toxicity (DLT)</title>
          <description>Toxicities were graded using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. A DLT was considered as any of the below, if judged by the investigator to be related to either treatment:&#xD;
Grade ≥ 4 neutropenia (absolute neutrophil count [ANC] &lt; 500/μl) lasting ≥ 7 days&#xD;
Grade ≥ 3 febrile neutropenia&#xD;
Grade ≥ 4 thrombocytopenia&#xD;
Grade ≥ 4 anemia&#xD;
Grade ≥ 4 rash&#xD;
Serious herpetic events&#xD;
Grade ≥ 3 symptomatic hepatic toxicities that do not resolve to Grade ≤ 2 within 48 hours or Grade ≥ 3 asymptomatic hepatic toxicities that do not resolve to Grade ≤ 1 within 3 weeks of onset&#xD;
Grade ≥ 3 non-hematologic, non-hepatic organ toxicity&#xD;
Grade 5 toxicity (ie, death)&#xD;
Any other intolerable toxicity leading to permanent discontinuation of treatment&#xD;
DLTs were to occur within the DLT evaluation period, defined as the period between the initial 10^6 PFU/mL dose and 3 weeks following the initial 10^8 PFU/mL dose or the start of Cycle 3, whichever occurred first.</description>
          <population>DLT Analysis Set: All participants who had opportunity to receive treatment for 2 cycles from the time of initial dose of study treatment and who had received 2 doses of talimogene laherparepvec and 2 doses of atezolizumab in combination or had a DLT during the DLT-evaluation period.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="5"/>
                <count group_id="O2" value="18"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Objective Response Rate (ORR)</title>
        <description>ORR was defined as the incidence rate of either a complete response (CR) or partial response (PR) based on modified immune-related response criteria simulating Response Evaluation Criteria in Solid Tumors(irRC-RECIST) criteria. A CR was a complete disappearance of all lesions and a PR was a decrease in tumor burden 30% or more relative to baseline.</description>
        <time_frame>Every 12 weeks (± 28 days) up to approximately 3.5 years.</time_frame>
        <population>Safety Analysis Set: All participants who received at least 1 dose of talimogene laherparepvec or atezolizumab.</population>
        <group_list>
          <group group_id="O1">
            <title>Talimogene Laherparepvec With Atezolizumab: Triple Negative Breast Cancer (TNBC)</title>
            <description>Participants with TNBC with liver metastases were administered intrahepatic injection of talimogene laherparepvec into liver metastases via guided injection (either ultrasound or computerized tomography) on Day 1 of each cycle for a maximum of 12 cycles, where each cycle was 21 days. Participants were administered 10^6 plaque-forming units/milliliter (PFU/mL) on Day 1 of Cycle 1 and 10^8 PFU/mL on Day 1 of each cycle thereafter. Participants were also administered 1200 mg atezolizumab via intravenous injection on Day 1 of each cycle.</description>
          </group>
          <group group_id="O2">
            <title>Talimogene Laherparepvec With Atezolizumab: Colorectal Cancer (CRC)</title>
            <description>Participants with CRC with liver metastases were administered intrahepatic injection of talimogene laherparepvec into liver metastases via guided injection (either ultrasound or computerized tomography) on Day 1 of each cycle for a maximum of 12 cycles, where each cycle was 21 days. Participants were administered 10^6 PFU/mL on Day 1 of Cycle 1 and 10^8 PFU/mL on Day 1 of each cycle thereafter. Participants were also administered 1200 mg atezolizumab via intravenous injection on Day 1 of each cycle.</description>
          </group>
        </group_list>
        <measure>
          <title>Objective Response Rate (ORR)</title>
          <description>ORR was defined as the incidence rate of either a complete response (CR) or partial response (PR) based on modified immune-related response criteria simulating Response Evaluation Criteria in Solid Tumors(irRC-RECIST) criteria. A CR was a complete disappearance of all lesions and a PR was a decrease in tumor burden 30% or more relative to baseline.</description>
          <population>Safety Analysis Set: All participants who received at least 1 dose of talimogene laherparepvec or atezolizumab.</population>
          <units>Percentage of Participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
                <count group_id="O2" value="24"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10.0" lower_limit="0.3" upper_limit="44.5"/>
                    <measurement group_id="O2" value="0.0" lower_limit="0.0" upper_limit="14.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Best Overall Response (BOR)</title>
        <description>BOR was defined as the best visit response based on modified irRC-RECIST criteria:&#xD;
CR: a complete disappearance of all lesions&#xD;
PR: a decrease in tumor burden 30% or more relative to baseline&#xD;
Stable disease (SD): neither sufficient shrinkage to qualify for CR or PR nor sufficient increase to qualify for progressive disease (PD)&#xD;
PD: an increase in tumor burden of 20% or more and at least 5 mm absolute increase relative to nadir (minimum recorded tumor burden)&#xD;
Unevaluable (UE): any lesion present at baseline which was not assessed or was unable to be evaluated leading to an inability to determine the status of that particular tumor</description>
        <time_frame>Every 12 weeks (± 28 days) up to approximately 3.5 years.</time_frame>
        <population>Safety Analysis Set: All participants who received at least 1 dose of talimogene laherparepvec or atezolizumab.</population>
        <group_list>
          <group group_id="O1">
            <title>Talimogene Laherparepvec With Atezolizumab: Triple Negative Breast Cancer (TNBC)</title>
            <description>Participants with TNBC with liver metastases were administered intrahepatic injection of talimogene laherparepvec into liver metastases via guided injection (either ultrasound or computerized tomography) on Day 1 of each cycle for a maximum of 12 cycles, where each cycle was 21 days. Participants were administered 10^6 plaque-forming units/milliliter (PFU/mL) on Day 1 of Cycle 1 and 10^8 PFU/mL on Day 1 of each cycle thereafter. Participants were also administered 1200 mg atezolizumab via intravenous injection on Day 1 of each cycle.</description>
          </group>
          <group group_id="O2">
            <title>Talimogene Laherparepvec With Atezolizumab: Colorectal Cancer (CRC)</title>
            <description>Participants with CRC with liver metastases were administered intrahepatic injection of talimogene laherparepvec into liver metastases via guided injection (either ultrasound or computerized tomography) on Day 1 of each cycle for a maximum of 12 cycles, where each cycle was 21 days. Participants were administered 10^6 PFU/mL on Day 1 of Cycle 1 and 10^8 PFU/mL on Day 1 of each cycle thereafter. Participants were also administered 1200 mg atezolizumab via intravenous injection on Day 1 of each cycle.</description>
          </group>
        </group_list>
        <measure>
          <title>Best Overall Response (BOR)</title>
          <description>BOR was defined as the best visit response based on modified irRC-RECIST criteria:&#xD;
CR: a complete disappearance of all lesions&#xD;
PR: a decrease in tumor burden 30% or more relative to baseline&#xD;
Stable disease (SD): neither sufficient shrinkage to qualify for CR or PR nor sufficient increase to qualify for progressive disease (PD)&#xD;
PD: an increase in tumor burden of 20% or more and at least 5 mm absolute increase relative to nadir (minimum recorded tumor burden)&#xD;
Unevaluable (UE): any lesion present at baseline which was not assessed or was unable to be evaluated leading to an inability to determine the status of that particular tumor</description>
          <population>Safety Analysis Set: All participants who received at least 1 dose of talimogene laherparepvec or atezolizumab.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
                <count group_id="O2" value="24"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>CR</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>PR</title>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>SD</title>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>PD</title>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>UE</title>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="14"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not done</title>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Duration of Response (DOR)</title>
        <description>DOR was defined as the time from the date of an initial response that is subsequently confirmed to the earlier of PD per modified irRC RECIST or death. Participants who have not ended their response at the time of analysis were censored at the last evaluable tumor assessment.</description>
        <time_frame>Every 12 weeks (± 28 days) up to approximately 3.5 years.</time_frame>
        <population>Responders in Safety Analysis Set: All participants in safety analysis set who received at least 1 dose of talimogene laherparepvec or atezolizumab who had a best overall response of CR/PR at the time of analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Talimogene Laherparepvec With Atezolizumab: Triple Negative Breast Cancer (TNBC)</title>
            <description>Participants with TNBC with liver metastases were administered intrahepatic injection of talimogene laherparepvec into liver metastases via guided injection (either ultrasound or computerized tomography) on Day 1 of each cycle for a maximum of 12 cycles, where each cycle was 21 days. Participants were administered 10^6 plaque-forming units/milliliter (PFU/mL) on Day 1 of Cycle 1 and 10^8 PFU/mL on Day 1 of each cycle thereafter. Participants were also administered 1200 mg atezolizumab via intravenous injection on Day 1 of each cycle.</description>
          </group>
          <group group_id="O2">
            <title>Talimogene Laherparepvec With Atezolizumab: Colorectal Cancer (CRC)</title>
            <description>Participants with CRC with liver metastases were administered intrahepatic injection of talimogene laherparepvec into liver metastases via guided injection (either ultrasound or computerized tomography) on Day 1 of each cycle for a maximum of 12 cycles, where each cycle was 21 days. Participants were administered 10^6 PFU/mL on Day 1 of Cycle 1 and 10^8 PFU/mL on Day 1 of each cycle thereafter. Participants were also administered 1200 mg atezolizumab via intravenous injection on Day 1 of each cycle.</description>
          </group>
        </group_list>
        <measure>
          <title>Duration of Response (DOR)</title>
          <description>DOR was defined as the time from the date of an initial response that is subsequently confirmed to the earlier of PD per modified irRC RECIST or death. Participants who have not ended their response at the time of analysis were censored at the last evaluable tumor assessment.</description>
          <population>Responders in Safety Analysis Set: All participants in safety analysis set who received at least 1 dose of talimogene laherparepvec or atezolizumab who had a best overall response of CR/PR at the time of analysis.</population>
          <units>Months</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="1"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="NA" lower_limit="NA" upper_limit="NA">Not calculable as only 1 participant achieved response.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Lesion Level Response in Injected Tumor Lesions</title>
        <description>Responses for individual tumor lesions for hepatic and non-hepatic tumors injected wtih treatment were assessed for the following responses:&#xD;
Lesion complete response rate (L-CRR): Disappearance of lesion&#xD;
Lesion partial response rate (L-PRR): Decrease in tumor burden 30% or more relative to baseline&#xD;
Lesion objective response rate (L-ORR): Either a L-CRR or L-PRR based on modified irRC-RECIST criteria</description>
        <time_frame>Every 12 weeks (± 28 days) up to approximately 3.5 years.</time_frame>
        <population>Injected Lesion Analysis Set: Any target lesion and new measurable lesion that was injected from the participants who had received at least 1 dose of talimogene laherparepvec or atezolizumab.</population>
        <group_list>
          <group group_id="O1">
            <title>Talimogene Laherparepvec With Atezolizumab: Triple Negative Breast Cancer (TNBC)</title>
            <description>Participants with TNBC with liver metastases were administered intrahepatic injection of talimogene laherparepvec into liver metastases via guided injection (either ultrasound or computerized tomography) on Day 1 of each cycle for a maximum of 12 cycles, where each cycle was 21 days. Participants were administered 10^6 plaque-forming units/milliliter (PFU/mL) on Day 1 of Cycle 1 and 10^8 PFU/mL on Day 1 of each cycle thereafter. Participants were also administered 1200 mg atezolizumab via intravenous injection on Day 1 of each cycle.</description>
          </group>
          <group group_id="O2">
            <title>Talimogene Laherparepvec With Atezolizumab: Colorectal Cancer (CRC)</title>
            <description>Participants with CRC with liver metastases were administered intrahepatic injection of talimogene laherparepvec into liver metastases via guided injection (either ultrasound or computerized tomography) on Day 1 of each cycle for a maximum of 12 cycles, where each cycle was 21 days. Participants were administered 10^6 PFU/mL on Day 1 of Cycle 1 and 10^8 PFU/mL on Day 1 of each cycle thereafter. Participants were also administered 1200 mg atezolizumab via intravenous injection on Day 1 of each cycle.</description>
          </group>
        </group_list>
        <measure>
          <title>Lesion Level Response in Injected Tumor Lesions</title>
          <description>Responses for individual tumor lesions for hepatic and non-hepatic tumors injected wtih treatment were assessed for the following responses:&#xD;
Lesion complete response rate (L-CRR): Disappearance of lesion&#xD;
Lesion partial response rate (L-PRR): Decrease in tumor burden 30% or more relative to baseline&#xD;
Lesion objective response rate (L-ORR): Either a L-CRR or L-PRR based on modified irRC-RECIST criteria</description>
          <population>Injected Lesion Analysis Set: Any target lesion and new measurable lesion that was injected from the participants who had received at least 1 dose of talimogene laherparepvec or atezolizumab.</population>
          <units>Lesions</units>
          <param>Count of Units</param>
          <units_analyzed>Lesions</units_analyzed>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="8"/>
                <count group_id="O2" value="20"/>
              </count_list>
            </analyzed>
            <analyzed>
              <units>Lesions</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="13"/>
                <count group_id="O2" value="28"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>L-CRR - Hepatic</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="8"/>
                    <count group_id="O2" value="20"/>
                  </count_list>
                </analyzed>
                <analyzed>
                  <units>Lesions</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="13"/>
                    <count group_id="O2" value="28"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0" lower_limit="0.0" upper_limit="24.7"/>
                    <measurement group_id="O2" value="0" lower_limit="0.0" upper_limit="12.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>L-CRR - Non-hepatic</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="0"/>
                    <count group_id="O2" value="0"/>
                  </count_list>
                </analyzed>
                <analyzed>
                  <units>Lesions</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="0"/>
                    <count group_id="O2" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
            </class>
            <class>
              <title>L-CRR - Overall</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="8"/>
                    <count group_id="O2" value="20"/>
                  </count_list>
                </analyzed>
                <analyzed>
                  <units>Lesions</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="13"/>
                    <count group_id="O2" value="28"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0" lower_limit="0.0" upper_limit="24.7"/>
                    <measurement group_id="O2" value="0" lower_limit="0.0" upper_limit="12.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>L-PRR - Hepatic</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="8"/>
                    <count group_id="O2" value="20"/>
                  </count_list>
                </analyzed>
                <analyzed>
                  <units>Lesions</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="13"/>
                    <count group_id="O2" value="28"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1" lower_limit="0.2" upper_limit="36.0"/>
                    <measurement group_id="O2" value="0" lower_limit="0.0" upper_limit="12.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>L-PRR - Non-hepatic</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="0"/>
                    <count group_id="O2" value="0"/>
                  </count_list>
                </analyzed>
                <analyzed>
                  <units>Lesions</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="0"/>
                    <count group_id="O2" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
            </class>
            <class>
              <title>L-PRR - Overall</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="8"/>
                    <count group_id="O2" value="20"/>
                  </count_list>
                </analyzed>
                <analyzed>
                  <units>Lesions</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="13"/>
                    <count group_id="O2" value="28"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1" lower_limit="0.2" upper_limit="36.0"/>
                    <measurement group_id="O2" value="0" lower_limit="0.0" upper_limit="12.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>L-ORR - Hepatic</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="8"/>
                    <count group_id="O2" value="20"/>
                  </count_list>
                </analyzed>
                <analyzed>
                  <units>Lesions</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="13"/>
                    <count group_id="O2" value="28"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1" lower_limit="0.2" upper_limit="36.0"/>
                    <measurement group_id="O2" value="0" lower_limit="0.0" upper_limit="12.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>L-ORR - Non-hepatic</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="0"/>
                    <count group_id="O2" value="0"/>
                  </count_list>
                </analyzed>
                <analyzed>
                  <units>Lesions</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="0"/>
                    <count group_id="O2" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
            </class>
            <class>
              <title>L-ORR - Overall</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="8"/>
                    <count group_id="O2" value="20"/>
                  </count_list>
                </analyzed>
                <analyzed>
                  <units>Lesions</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="13"/>
                    <count group_id="O2" value="28"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1" lower_limit="0.2" upper_limit="36.0"/>
                    <measurement group_id="O2" value="0" lower_limit="0.0" upper_limit="12.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Lesion Level Response in Uninjected Tumor Lesions</title>
        <description>Responses for individual tumor lesions for hepatic and non-hepatic tumors that were not injected with treatment were assessed for the following responses:&#xD;
L-CRR: Disappearance of lesion&#xD;
L-PRR: Decrease in tumor burden 30% or more relative to baseline&#xD;
L-ORR: Either a L-CRR or L-PRR based on modified irRC-RECIST criteria</description>
        <time_frame>Every 12 weeks (± 28 days) up to approximately 3.5 years.</time_frame>
        <population>Uninjected Lesion Analysis Set: Any target lesion and new measurable lesion that was never injected from the participants who had received at least 1 dose of talimogene laherparepvec or atezolizumab.</population>
        <group_list>
          <group group_id="O1">
            <title>Talimogene Laherparepvec With Atezolizumab: Triple Negative Breast Cancer (TNBC)</title>
            <description>Participants with TNBC with liver metastases were administered intrahepatic injection of talimogene laherparepvec into liver metastases via guided injection (either ultrasound or computerized tomography) on Day 1 of each cycle for a maximum of 12 cycles, where each cycle was 21 days. Participants were administered 10^6 plaque-forming units/milliliter (PFU/mL) on Day 1 of Cycle 1 and 10^8 PFU/mL on Day 1 of each cycle thereafter. Participants were also administered 1200 mg atezolizumab via intravenous injection on Day 1 of each cycle.</description>
          </group>
          <group group_id="O2">
            <title>Talimogene Laherparepvec With Atezolizumab: Colorectal Cancer (CRC)</title>
            <description>Participants with CRC with liver metastases were administered intrahepatic injection of talimogene laherparepvec into liver metastases via guided injection (either ultrasound or computerized tomography) on Day 1 of each cycle for a maximum of 12 cycles, where each cycle was 21 days. Participants were administered 10^6 PFU/mL on Day 1 of Cycle 1 and 10^8 PFU/mL on Day 1 of each cycle thereafter. Participants were also administered 1200 mg atezolizumab via intravenous injection on Day 1 of each cycle.</description>
          </group>
        </group_list>
        <measure>
          <title>Lesion Level Response in Uninjected Tumor Lesions</title>
          <description>Responses for individual tumor lesions for hepatic and non-hepatic tumors that were not injected with treatment were assessed for the following responses:&#xD;
L-CRR: Disappearance of lesion&#xD;
L-PRR: Decrease in tumor burden 30% or more relative to baseline&#xD;
L-ORR: Either a L-CRR or L-PRR based on modified irRC-RECIST criteria</description>
          <population>Uninjected Lesion Analysis Set: Any target lesion and new measurable lesion that was never injected from the participants who had received at least 1 dose of talimogene laherparepvec or atezolizumab.</population>
          <units>Lesions</units>
          <param>Count of Units</param>
          <units_analyzed>Lesions</units_analyzed>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
                <count group_id="O2" value="22"/>
              </count_list>
            </analyzed>
            <analyzed>
              <units>Lesions</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="24"/>
                <count group_id="O2" value="94"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>L-CRR - Hepatic</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="10"/>
                    <count group_id="O2" value="22"/>
                  </count_list>
                </analyzed>
                <analyzed>
                  <units>Lesions</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="15"/>
                    <count group_id="O2" value="50"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0" lower_limit="0.0" upper_limit="21.8"/>
                    <measurement group_id="O2" value="0" lower_limit="0.0" upper_limit="7.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>L-CRR - Non-hepatic</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="10"/>
                    <count group_id="O2" value="22"/>
                  </count_list>
                </analyzed>
                <analyzed>
                  <units>Lesions</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="9"/>
                    <count group_id="O2" value="44"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0" lower_limit="0.0" upper_limit="33.6"/>
                    <measurement group_id="O2" value="0" lower_limit="0.0" upper_limit="8.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>L-CRR - Overall</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="10"/>
                    <count group_id="O2" value="22"/>
                  </count_list>
                </analyzed>
                <analyzed>
                  <units>Lesions</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="24"/>
                    <count group_id="O2" value="94"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0" lower_limit="0.0" upper_limit="14.2"/>
                    <measurement group_id="O2" value="0" lower_limit="0.0" upper_limit="3.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>L-PRR - Hepatic</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="10"/>
                    <count group_id="O2" value="22"/>
                  </count_list>
                </analyzed>
                <analyzed>
                  <units>Lesions</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="15"/>
                    <count group_id="O2" value="50"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0" lower_limit="0.0" upper_limit="21.8"/>
                    <measurement group_id="O2" value="1" lower_limit="0.1" upper_limit="10.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>L-PRR - Non-hepatic</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="10"/>
                    <count group_id="O2" value="22"/>
                  </count_list>
                </analyzed>
                <analyzed>
                  <units>Lesions</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="9"/>
                    <count group_id="O2" value="44"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1" lower_limit="0.3" upper_limit="48.2"/>
                    <measurement group_id="O2" value="0" lower_limit="0.0" upper_limit="8.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>L-PRR - Overall</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="10"/>
                    <count group_id="O2" value="22"/>
                  </count_list>
                </analyzed>
                <analyzed>
                  <units>Lesions</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="24"/>
                    <count group_id="O2" value="94"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1" lower_limit="0.1" upper_limit="21.1"/>
                    <measurement group_id="O2" value="1" lower_limit="0.0" upper_limit="5.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>L-ORR - Hepatic</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="10"/>
                    <count group_id="O2" value="22"/>
                  </count_list>
                </analyzed>
                <analyzed>
                  <units>Lesions</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="15"/>
                    <count group_id="O2" value="50"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0" lower_limit="0.0" upper_limit="21.8"/>
                    <measurement group_id="O2" value="1" lower_limit="0.1" upper_limit="10.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>L-ORR - Non-hepatic</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="10"/>
                    <count group_id="O2" value="22"/>
                  </count_list>
                </analyzed>
                <analyzed>
                  <units>Lesions</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="9"/>
                    <count group_id="O2" value="44"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1" lower_limit="0.3" upper_limit="48.2"/>
                    <measurement group_id="O2" value="0" lower_limit="0.0" upper_limit="8.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>L-ORR - Overall</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="10"/>
                    <count group_id="O2" value="22"/>
                  </count_list>
                </analyzed>
                <analyzed>
                  <units>Lesions</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="24"/>
                    <count group_id="O2" value="94"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1" lower_limit="0.1" upper_limit="21.1"/>
                    <measurement group_id="O2" value="1" lower_limit="0.0" upper_limit="5.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Durable Response Rate (DRR)</title>
        <description>DRR was defined as the percentage of participants with an objective response with a DOR of at least 6 months.</description>
        <time_frame>Every 12 weeks (± 28 days) up to approximately 3.5 years.</time_frame>
        <population>Safety Analysis Set: All participants who received at least 1 dose of talimogene laherparepvec or atezolizumab.</population>
        <group_list>
          <group group_id="O1">
            <title>Talimogene Laherparepvec With Atezolizumab: Triple Negative Breast Cancer (TNBC)</title>
            <description>Participants with TNBC with liver metastases were administered intrahepatic injection of talimogene laherparepvec into liver metastases via guided injection (either ultrasound or computerized tomography) on Day 1 of each cycle for a maximum of 12 cycles, where each cycle was 21 days. Participants were administered 10^6 plaque-forming units/milliliter (PFU/mL) on Day 1 of Cycle 1 and 10^8 PFU/mL on Day 1 of each cycle thereafter. Participants were also administered 1200 mg atezolizumab via intravenous injection on Day 1 of each cycle.</description>
          </group>
          <group group_id="O2">
            <title>Talimogene Laherparepvec With Atezolizumab: Colorectal Cancer (CRC)</title>
            <description>Participants with CRC with liver metastases were administered intrahepatic injection of talimogene laherparepvec into liver metastases via guided injection (either ultrasound or computerized tomography) on Day 1 of each cycle for a maximum of 12 cycles, where each cycle was 21 days. Participants were administered 10^6 PFU/mL on Day 1 of Cycle 1 and 10^8 PFU/mL on Day 1 of each cycle thereafter. Participants were also administered 1200 mg atezolizumab via intravenous injection on Day 1 of each cycle.</description>
          </group>
        </group_list>
        <measure>
          <title>Durable Response Rate (DRR)</title>
          <description>DRR was defined as the percentage of participants with an objective response with a DOR of at least 6 months.</description>
          <population>Safety Analysis Set: All participants who received at least 1 dose of talimogene laherparepvec or atezolizumab.</population>
          <units>Percentage of Participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
                <count group_id="O2" value="24"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0" lower_limit="0.0" upper_limit="30.8"/>
                    <measurement group_id="O2" value="0.0" lower_limit="0.0" upper_limit="14.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Disease Control Rate (DCR)</title>
        <description>DCR was defined as the percentage of participants that have a best overall response in one of the following categories: CR/PR/SD.</description>
        <time_frame>Every 12 weeks (± 28 days) up to approximately 3.5 years.</time_frame>
        <population>Safety Analysis Set: All participants who received at least 1 dose of talimogene laherparepvec or atezolizumab.</population>
        <group_list>
          <group group_id="O1">
            <title>Talimogene Laherparepvec With Atezolizumab: Triple Negative Breast Cancer (TNBC)</title>
            <description>Participants with TNBC with liver metastases were administered intrahepatic injection of talimogene laherparepvec into liver metastases via guided injection (either ultrasound or computerized tomography) on Day 1 of each cycle for a maximum of 12 cycles, where each cycle was 21 days. Participants were administered 10^6 plaque-forming units/milliliter (PFU/mL) on Day 1 of Cycle 1 and 10^8 PFU/mL on Day 1 of each cycle thereafter. Participants were also administered 1200 mg atezolizumab via intravenous injection on Day 1 of each cycle.</description>
          </group>
          <group group_id="O2">
            <title>Talimogene Laherparepvec With Atezolizumab: Colorectal Cancer (CRC)</title>
            <description>Participants with CRC with liver metastases were administered intrahepatic injection of talimogene laherparepvec into liver metastases via guided injection (either ultrasound or computerized tomography) on Day 1 of each cycle for a maximum of 12 cycles, where each cycle was 21 days. Participants were administered 10^6 PFU/mL on Day 1 of Cycle 1 and 10^8 PFU/mL on Day 1 of each cycle thereafter. Participants were also administered 1200 mg atezolizumab via intravenous injection on Day 1 of each cycle.</description>
          </group>
        </group_list>
        <measure>
          <title>Disease Control Rate (DCR)</title>
          <description>DCR was defined as the percentage of participants that have a best overall response in one of the following categories: CR/PR/SD.</description>
          <population>Safety Analysis Set: All participants who received at least 1 dose of talimogene laherparepvec or atezolizumab.</population>
          <units>Percentage of Participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
                <count group_id="O2" value="24"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="20.0" lower_limit="2.5" upper_limit="55.6"/>
                    <measurement group_id="O2" value="4.2" lower_limit="0.1" upper_limit="21.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Progression-free Survival (PFS)</title>
        <description>PFS was defined as time from first dose to the date of first of confirmed disease progression per modified irRC-RECIST criteria, or death (whichever occurred first). Results were estimated using the Kaplan-Meier method.</description>
        <time_frame>Every 12 weeks (± 28 days) up to approximately 3.5 years.</time_frame>
        <population>Safety Analysis Set: All participants who received at least 1 dose of talimogene laherparepvec or atezolizumab.</population>
        <group_list>
          <group group_id="O1">
            <title>Talimogene Laherparepvec With Atezolizumab: Triple Negative Breast Cancer (TNBC)</title>
            <description>Participants with TNBC with liver metastases were administered intrahepatic injection of talimogene laherparepvec into liver metastases via guided injection (either ultrasound or computerized tomography) on Day 1 of each cycle for a maximum of 12 cycles, where each cycle was 21 days. Participants were administered 10^6 plaque-forming units/milliliter (PFU/mL) on Day 1 of Cycle 1 and 10^8 PFU/mL on Day 1 of each cycle thereafter. Participants were also administered 1200 mg atezolizumab via intravenous injection on Day 1 of each cycle.</description>
          </group>
          <group group_id="O2">
            <title>Talimogene Laherparepvec With Atezolizumab: Colorectal Cancer (CRC)</title>
            <description>Participants with CRC with liver metastases were administered intrahepatic injection of talimogene laherparepvec into liver metastases via guided injection (either ultrasound or computerized tomography) on Day 1 of each cycle for a maximum of 12 cycles, where each cycle was 21 days. Participants were administered 10^6 PFU/mL on Day 1 of Cycle 1 and 10^8 PFU/mL on Day 1 of each cycle thereafter. Participants were also administered 1200 mg atezolizumab via intravenous injection on Day 1 of each cycle.</description>
          </group>
        </group_list>
        <measure>
          <title>Progression-free Survival (PFS)</title>
          <description>PFS was defined as time from first dose to the date of first of confirmed disease progression per modified irRC-RECIST criteria, or death (whichever occurred first). Results were estimated using the Kaplan-Meier method.</description>
          <population>Safety Analysis Set: All participants who received at least 1 dose of talimogene laherparepvec or atezolizumab.</population>
          <units>Months</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
                <count group_id="O2" value="24"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.4" lower_limit="1.0" upper_limit="NA">Upper limit was not estimable.</measurement>
                    <measurement group_id="O2" value="3.1" lower_limit="2.1" upper_limit="5.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Overall Survival (OS)</title>
        <description>OS was defined as the time from the date of first dose to the date of death from any cause. Results were estimated using the Kaplan-Meier method.</description>
        <time_frame>Every 12 weeks (± 28 days) up to approximately 3.5 years.</time_frame>
        <population>Safety Analysis Set: All participants who received at least 1 dose of talimogene laherparepvec or atezolizumab.</population>
        <group_list>
          <group group_id="O1">
            <title>Talimogene Laherparepvec With Atezolizumab: Triple Negative Breast Cancer (TNBC)</title>
            <description>Participants with TNBC with liver metastases were administered intrahepatic injection of talimogene laherparepvec into liver metastases via guided injection (either ultrasound or computerized tomography) on Day 1 of each cycle for a maximum of 12 cycles, where each cycle was 21 days. Participants were administered 10^6 plaque-forming units/milliliter (PFU/mL) on Day 1 of Cycle 1 and 10^8 PFU/mL on Day 1 of each cycle thereafter. Participants were also administered 1200 mg atezolizumab via intravenous injection on Day 1 of each cycle.</description>
          </group>
          <group group_id="O2">
            <title>Talimogene Laherparepvec With Atezolizumab: Colorectal Cancer (CRC)</title>
            <description>Participants with CRC with liver metastases were administered intrahepatic injection of talimogene laherparepvec into liver metastases via guided injection (either ultrasound or computerized tomography) on Day 1 of each cycle for a maximum of 12 cycles, where each cycle was 21 days. Participants were administered 10^6 PFU/mL on Day 1 of Cycle 1 and 10^8 PFU/mL on Day 1 of each cycle thereafter. Participants were also administered 1200 mg atezolizumab via intravenous injection on Day 1 of each cycle.</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Survival (OS)</title>
          <description>OS was defined as the time from the date of first dose to the date of death from any cause. Results were estimated using the Kaplan-Meier method.</description>
          <population>Safety Analysis Set: All participants who received at least 1 dose of talimogene laherparepvec or atezolizumab.</population>
          <units>Months</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
                <count group_id="O2" value="24"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="19.2" lower_limit="1.5" upper_limit="NA">Upper limit was not estimable.</measurement>
                    <measurement group_id="O2" value="4.0" lower_limit="2.8" upper_limit="6.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Day 1 up to approximately 3.5 years.</time_frame>
      <desc>All-Cause Mortality is reported for all enrolled participants. Serious and Other Adverse Events are reported for the Safety Analysis Set defined as all participants who received at least 1 dose of talimogene laherparepvec or atezolizumab.</desc>
      <group_list>
        <group group_id="E1">
          <title>Talimogene Laherparepvec With Atezolizumab: Triple Negative Breast Cancer (TNBC)</title>
          <description>Participants with TNBC with liver metastases were administered intrahepatic injection of talimogene laherparepvec into liver metastases via guided injection (either ultrasound or computerized tomography) on Day 1 of each cycle for a maximum of 12 cycles, where each cycle was 21 days. Participants were administered 10^6 plaque-forming units/milliliter (PFU/mL) on Day 1 of Cycle 1 and 10^8 PFU/mL on Day 1 of each cycle thereafter. Participants were also administered 1200 mg atezolizumab via intravenous injection on Day 1 of each cycle.</description>
        </group>
        <group group_id="E2">
          <title>Talimogene Laherparepvec With Atezolizumab: Colorectal Cancer (CRC)</title>
          <description>Participants with CRC with liver metastases were administered intrahepatic injection of talimogene laherparepvec into liver metastases via guided injection (either ultrasound or computerized tomography) on Day 1 of each cycle for a maximum of 12 cycles, where each cycle was 21 days. Participants were administered 10^6 PFU/mL on Day 1 of Cycle 1 and 10^8 PFU/mL on Day 1 of each cycle thereafter. Participants were also administered 1200 mg atezolizumab via intravenous injection on Day 1 of each cycle.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA 24.1</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="22" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="12" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Cardiac failure</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Myocarditis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Intra-abdominal fluid collection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Hepatic haematoma</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>Cytokine release syndrome</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Hypersensitivity</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Abdominal infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Pulmonary sepsis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Viral infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Electrocardiogram QT prolonged</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Platelet count decreased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hyponatraemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Colorectal cancer metastatic</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Tumour hyperprogression</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Acute kidney injury</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Respiratory failure</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Orthostatic hypotension</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA 24.1</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="23" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Tachycardia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Ear congestion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Ear pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Dry eye</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Abdominal pain lower</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Abdominal pain upper</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Flatulence</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Impaired gastric emptying</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Asthenia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Chills</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>General physical health deterioration</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Influenza like illness</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Injection site pain</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Oedema peripheral</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="14" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Hepatic pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>Cytokine release syndrome</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Herpes virus infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Contusion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Infusion related reaction</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Blood alkaline phosphatase increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Hepatic enzyme increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Lymphocyte count decreased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Platelet count decreased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Decreased appetite</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Hypokalaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Bone pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Musculoskeletal pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Myalgia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Neck pain</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Lethargy</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Presyncope</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Dysuria</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Benign prostatic hyperplasia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Vulvovaginal pruritus</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Epistaxis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Hiccups</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Rash macular</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Rash maculo-papular</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hot flush</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>The Clinical Trial Agreement generally does not restrict an investigator's discussion of trial results after completion. The Agreement permits Amgen a limited period of time to review material discussing trial results (typically up to 45 days and possible extension). Amgen may remove confidential information, but authors have final control and approval of publication content. For multicenter studies, the investigator agrees not to publish any results before the first multi-center publication.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Study Director</name_or_title>
      <organization>Amgen Inc.</organization>
      <phone>866-572-6436</phone>
      <email>medinfo@amgen.com</email>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03256344
org study id: 20140299
nct id: NCT03256344
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
Approximately 36 DLT-evaluable subjects will be enrolled in this study. The locations of the
      study will be in the United States, Australia, Europe and Switzerland.

      The goal of this study is to evaluate the safety of intrahepatic injection (directly into the
      liver) of talimogene laherparepvec in combination with intravenously administered
      atezolizumab in subjects with triple negative breast cancer and colorectal cancer with liver
      metastases.
The Screening period is 28 days prior to study enrollment. This study has 2 Cohorts. Cohort
      1: Triple Negative Breast Cancer and Cohort 2: Colorectal Cancer. These cohorts will enroll
      in parallel. There will be a Safety Follow-up period and a Long Term Follow-up period.

      Drug Administration: The participants will receive the study drugs in cycles. If the
      participants are found to be eligible to take part in this study, they will receive
      talimogene laherparepvec as an injection into the hepatic (liver) metastatic sites on Day 1
      of each cycle along with receiving atezolizumab by intravenous infusion on Day 1 of each
      cycle. Each cycle is 21 days for 6 cycles. There is an option for an additional 6 cycles
      after the first 6 intra-hepatic cycles. After the first radiographic assessment at week 10,
      if all injectable liver lesions have been injected but the 4.0 mL maximum volume has not been
      used, injection of clinically assessed non-hepatic cutaneous, subcutaneous, and nodal tumor
      lesions with or without ultrasound guidance will be permitted. Liver lesions should be
      prioritized over cutaneous, subcutaneous and nodal lesions.

      Treatment will continue until a participant experiences a DLT (Dose Limiting Toxicity)
      evaluated in the DLT period (which is 2 cycles from initial dose), has CR (Complete
      Response), has need for an alternative anticancer therapy or experiences a safety concern.

      Study Visits: Cycle 1 to Cycle 12 - The participant will have a physical exam along with
      vital signs and ECOG (Eastern Cooperative Oncology Group) performance level assessment. Blood
      (about 2 Tablespoons) will be drawn for routine tests and to check the immune system. Adverse
      events and medications taken will be reviewed on each cycle.Biomarkers will be taken on
      cycles 1, 2, 3, 6, and safety FU. Tumor Markers (special lab tests associated with the
      cancer, such as particular proteins) will be completed will be take on cycles 1, 4, 7, 10,
      13, every 3 cycles and SFU.

      Central lab tests will be completed on cycles 1, 2, 3, and 6 and safety FU. Cycle 1 Archived
      (prior stored) tumor sample will be obtained. Also, a liver tumor biopsy will be completed at
      Cycles 1, 3 and 6.

      Response Assessments will be completed at Screening and again at Cycles 4, 7, 10, 13 and
      every 3 cycles.

      Throughout the trial a swab for Herpetic tumor will be obtained within 3 days of the event.

      Cycle 1 to 12- The exposure to talimogene laherparepvec by the subject's healthcare provider
      and household member caregiver will be reviewed. Cycles 1, 3, 6-Liver tumor biopsy will be
      completed. Cycles 4, 7, 10, 13 and every 3 cycles -Response assessments will be completed by
      radiographic and clinical tumor assessment.

      Length of Treatment:

      A maximum for 12 cycles of talimogene laherparepvec are allowed during the study. The
      participant may continue taking the study drug for as long as the doctor thinks it is in
      their best interest. The participant will no longer be able to take the study drug if the
      disease gets worse, or if they are unable to follow study directions.

      Safety Follow-up Visit:

      Safety Follow-up visit will be performed about 30 days after the last dose of study
      treatment.

      The participant will have a physical exam, have vital signs taken, assessment of ECOG status
      and have weight measured. Adverse events will be assessed as well as the concominant
      medications. Routine bloodwork and tumor markers will be taken.

      Exposure to talimogene laherparepvec by the healthcare providers of the participant and/or
      close contacts will be assessed.

      Long-Term Follow-up Visits: Participants will be followed for survival every 12 weeks from
      the date of the safety follow-up visit until approximately 24 months after the last subject
      is enrolled. Subsequent cancer treatments will be collected as part of the long-term
      follow-up survival assessment. This is an investigational study. The study doctor can explain
      how the study drugs are designed to work.
allocation: Non-Randomized
intervention model: Single Group Assignment
primary purpose: Other
masking: None (Open Label)
measure: Number of Participants Who Experienced a Dose-Limiting Toxicity (DLT)
time frame: From Day 1 up to the start of Cycle 3 (each cycle is 21 days)
description: Toxicities were graded using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. A DLT was considered as any of the below, if judged by the investigator to be related to either treatment:
Grade ≥ 4 neutropenia (absolute neutrophil count [ANC] < 500/μl) lasting ≥ 7 days
Grade ≥ 3 febrile neutropenia
Grade ≥ 4 thrombocytopenia
Grade ≥ 4 anemia
Grade ≥ 4 rash
Serious herpetic events
Grade ≥ 3 symptomatic hepatic toxicities that do not resolve to Grade ≤ 2 within 48 hours or Grade ≥ 3 asymptomatic hepatic toxicities that do not resolve to Grade ≤ 1 within 3 weeks of onset
Grade ≥ 3 non-hematologic, non-hepatic organ toxicity
Grade 5 toxicity (ie, death)
Any other intolerable toxicity leading to permanent discontinuation of treatment
DLTs were to occur within the DLT evaluation period, defined as the period between the initial 10^6 PFU/mL dose and 3 weeks following the initial 10^8 PFU/mL dose or the start of Cycle 3, whichever occurred first.
measure: Objective Response Rate (ORR)
time frame: Every 12 weeks (± 28 days) up to approximately 3.5 years.
description: ORR was defined as the incidence rate of either a complete response (CR) or partial response (PR) based on modified immune-related response criteria simulating Response Evaluation Criteria in Solid Tumors(irRC-RECIST) criteria. A CR was a complete disappearance of all lesions and a PR was a decrease in tumor burden 30% or more relative to baseline.
measure: Best Overall Response (BOR)
time frame: Every 12 weeks (± 28 days) up to approximately 3.5 years.
description: BOR was defined as the best visit response based on modified irRC-RECIST criteria:
CR: a complete disappearance of all lesions
PR: a decrease in tumor burden 30% or more relative to baseline
Stable disease (SD): neither sufficient shrinkage to qualify for CR or PR nor sufficient increase to qualify for progressive disease (PD)
PD: an increase in tumor burden of 20% or more and at least 5 mm absolute increase relative to nadir (minimum recorded tumor burden)
Unevaluable (UE): any lesion present at baseline which was not assessed or was unable to be evaluated leading to an inability to determine the status of that particular tumor
measure: Duration of Response (DOR)
time frame: Every 12 weeks (± 28 days) up to approximately 3.5 years.
description: DOR was defined as the time from the date of an initial response that is subsequently confirmed to the earlier of PD per modified irRC RECIST or death. Participants who have not ended their response at the time of analysis were censored at the last evaluable tumor assessment.
measure: Lesion Level Response in Injected Tumor Lesions
time frame: Every 12 weeks (± 28 days) up to approximately 3.5 years.
description: Responses for individual tumor lesions for hepatic and non-hepatic tumors injected wtih treatment were assessed for the following responses:
Lesion complete response rate (L-CRR): Disappearance of lesion
Lesion partial response rate (L-PRR): Decrease in tumor burden 30% or more relative to baseline
Lesion objective response rate (L-ORR): Either a L-CRR or L-PRR based on modified irRC-RECIST criteria
measure: Lesion Level Response in Uninjected Tumor Lesions
time frame: Every 12 weeks (± 28 days) up to approximately 3.5 years.
description: Responses for individual tumor lesions for hepatic and non-hepatic tumors that were not injected with treatment were assessed for the following responses:
L-CRR: Disappearance of lesion
L-PRR: Decrease in tumor burden 30% or more relative to baseline
L-ORR: Either a L-CRR or L-PRR based on modified irRC-RECIST criteria
measure: Durable Response Rate (DRR)
time frame: Every 12 weeks (± 28 days) up to approximately 3.5 years.
description: DRR was defined as the percentage of participants with an objective response with a DOR of at least 6 months.
measure: Disease Control Rate (DCR)
time frame: Every 12 weeks (± 28 days) up to approximately 3.5 years.
description: DCR was defined as the percentage of participants that have a best overall response in one of the following categories: CR/PR/SD.
measure: Progression-free Survival (PFS)
time frame: Every 12 weeks (± 28 days) up to approximately 3.5 years.
description: PFS was defined as time from first dose to the date of first of confirmed disease progression per modified irRC-RECIST criteria, or death (whichever occurred first). Results were estimated using the Kaplan-Meier method.
measure: Overall Survival (OS)
time frame: Every 12 weeks (± 28 days) up to approximately 3.5 years.
description: OS was defined as the time from the date of first dose to the date of death from any cause. Results were estimated using the Kaplan-Meier method.
arm group label: Talimogene Laherparepvec with Atezolizumab: Triple Negative Breast Cancer (TNBC)
arm group type: Experimental
description: Participants with TNBC with liver metastases administered intrahepatic injection of talimogene laherparepvec into liver metastases via guided injection (either ultrasound or computerized tomography) on Day 1 of each cycle for a maximum of 12 cycles, where each cycle is 21 days. Participants administered 10^6 plaque-forming units/milliliter (PFU/mL) on Day 1 of Cycle 1 and 10^8 PFU/mL on Day 1 of each cycle thereafter. Participants also administered 1200 mg atezolizumab via intravenous injection on Day 1 of each cycle.
arm group label: Talimogene Laherparepvec with Atezolizumab: Colorectal Cancer (CRC)
arm group type: Experimental
description: Participants with CRC with liver metastases administered intrahepatic injection of talimogene laherparepvec into liver metastases via guided injection (either ultrasound or computerized tomography) on Day 1 of each cycle for a maximum of 12 cycles, where each cycle is 21 days. Participants administered 10^6 PFU/mL on Day 1 of Cycle 1 and 10^8 PFU/mL on Day 1 of each cycle thereafter. Participants also administered 1200 mg atezolizumab via intravenous injection on Day 1 of each cycle.
intervention type: Biological
intervention name: Talimogene Laherparepvec
description: Virally based anti-cancer immunotherapy given by direct injection into tumors.
arm group label: Talimogene Laherparepvec with Atezolizumab: Colorectal Cancer (CRC)
arm group label: Talimogene Laherparepvec with Atezolizumab: Triple Negative Breast Cancer (TNBC)
other name: IMLYGIC
intervention type: Biological
intervention name: Atezolizumab
description: A monoclonal antibody given by intravenous injection.
arm group label: Talimogene Laherparepvec with Atezolizumab: Colorectal Cancer (CRC)
arm group label: Talimogene Laherparepvec with Atezolizumab: Triple Negative Breast Cancer (TNBC)
other name: MPDL3280A
criteria: 
gender: All
minimum age: 18 Years
maximum age: 99 Years
healthy volunteers: No
last name: MD
role: Study Director
affiliation: Amgen
facility: 
facility: 
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facility: 
country: Australia
country: Belgium
country: Germany
country: Spain
country: Switzerland
country: United States
url: http://www.amgentrials.com
description: AmgenTrials clinical trials website
responsible party type: Sponsor
mesh term: Breast Neoplasms
mesh term: Colorectal Neoplasms
mesh term: Neoplasm Metastasis
mesh term: Triple Negative Breast Neoplasms
mesh term: Atezolizumab
mesh term: Talimogene laherparepvec
sharing ipd: Yes
ipd description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Informed Consent Form (ICF)
ipd info type: Clinical Study Report (CSR)
ipd time frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
ipd access criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors. If not approved, a Data Sharing Independent Review Panel will arbitrate and make the final decision. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below.
ipd url: https://www.amgen.com/datasharing
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 