<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/NCT04468061</url>
  </required_header>
  <id_info>
    <org_study_id>20-166</org_study_id>
    <nct_id>NCT04468061</nct_id>
  </id_info>
  <brief_title>Sacituzumab Govitecan +/- Pembrolizumab in Metastatic TNBC</brief_title>
  <official_title>Saci-IO TNBC: Randomized Phase II Study of Sacituzumab Govitecan With or Without Pembrolizumab in PD-L1-negative Metastatic Triple Negative Breast Cancer (TNBC)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Dana-Farber Cancer Institute</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Gilead Sciences</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Merck Sharp &amp; Dohme LLC</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Dana-Farber Cancer Institute</source>
  <oversight_info>
    <has_dmc>Yes</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>
      This research study involves testing the safety and efficacy of an investigational&#xD;
      intervention for patients with triple-negative breast cancer (TNBC) that has spread, or&#xD;
      metastasized, to other parts the body and is PD-L1-negative.&#xD;
&#xD;
      The names of the study interventions involved in this study are:&#xD;
&#xD;
        -  Sacituzumab govitecan (Trodelvy™;IMMU-132)&#xD;
&#xD;
        -  Pembrolizumab (Keytruda®; MK-3475)&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This research study is a Phase II clinical trial. Phase II clinical trials test the safety&#xD;
      and effectiveness of an investigational drug or a combination of investigational drugs to&#xD;
      learn whether the drug or drug combination works in treating a specific disease.&#xD;
      &quot;Investigational&quot; means that the drug or drug combination is being studied.&#xD;
&#xD;
      The U.S. Food and Drug Administration (FDA) has approved Sacituzumab Govitecan for metastatic&#xD;
      triple-negative breast cancer, but it is currently approved only for patients who have had 2&#xD;
      or more prior regimens for metastatic disease. The U.S. Food and Drug Administration (FDA)&#xD;
      has approved Pembrolizumab for metastatic triple-negative breast cancer, but it is currently&#xD;
      approved only for patients with PD-L1-positive metastatic triple-negative breast cancer.&#xD;
&#xD;
      In this research study, we are:&#xD;
&#xD;
        -  Studying Sacituzumab Govitecan alone or in combination with Pembrolizumab as a possible&#xD;
           treatment for patients with metastatic triple-negative breast cancers that are&#xD;
           PD-L1-negative.&#xD;
&#xD;
        -  Sacituzumab Govitecan is composed of a chemotherapy drug, called Irinotecan, which is&#xD;
           attached to an antibody. Antibodies are proteins normally made by the immune system that&#xD;
           bind to substances that don't belong in the body to prevent harm. The antibody in this&#xD;
           study binds to certain types of cancer tumors, including triple-negative breast tumors.&#xD;
&#xD;
        -  Pembrolizumab is an immunotherapy, called an anti-PD-1 or a checkpoint inhibitor, and is&#xD;
           an antibody (a type of human protein) designed to allow the body's own immune system to&#xD;
           seek out and destroy tumors. It has been used in previous research studies to treat&#xD;
           breast cancer, where it has been shown to be effective.&#xD;
&#xD;
        -  The overall goal of this study is to evaluate the effectiveness of either Sacituzumab&#xD;
           Govitecan alone or in combination with Pembrolizumab, in delaying the worsening of&#xD;
           triple-negative breast cancers that are PD-L1-negative.&#xD;
&#xD;
      The research study procedures include: screening for eligibility, research blood collections,&#xD;
      at least two research biopsies, paired research stool collections, questionnaires, data&#xD;
      collection, and study treatment including evaluations and follow up visits.&#xD;
&#xD;
      Participants will be randomized into one of two groups.&#xD;
&#xD;
        -  Group A: Sacituzumab Govitecan on days 1 and 8 and Pembrolizumab on day 1 of a 21-day&#xD;
           cycle&#xD;
&#xD;
        -  Group B: Sacituzumab Govitecan alone on days 1 and 8 of a 21-day cycle&#xD;
&#xD;
      Participants will receive study treatment for as long as they are benefitting from this&#xD;
      therapy. Participants will be followed for the rest of their life.&#xD;
&#xD;
      It is expected that about 110 people will take part in this research study.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">July 20, 2020</start_date>
  <completion_date type="Anticipated">April 1, 2027</completion_date>
  <primary_completion_date type="Anticipated">April 1, 2024</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Progression Free Survival (PFS)</measure>
    <time_frame>3 years</time_frame>
    <description>Compare PFS of patients randomized to receive sacituzumab govitecan in combination with pembrolizumab (Arm A) versus those randomized to receive sacituzumab govitecan monotherapy (Arm B).&#xD;
Defined as the time from study randomization to disease progression, per RECIST 1.1 or medical judgment, the latter based on established clinical parameters, such as rising tumor markers and physical exam evidence of progression, i.e. worsening chest wall disease, or death due to any cause, whichever occurred first.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall Survival (OS)</measure>
    <time_frame>3 years</time_frame>
    <description>Compare the efficacy of sacituzumab govitecan with pembrolizumab to that of sacituzumab govitecan alone by assessing Overall Survival (OS), defined as the time from randomization (or registration) to death due to any cause, or censored at date last known alive, will be reported with Kaplan Meier estimates.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Objective Response Rate (ORR)</measure>
    <time_frame>3 years</time_frame>
    <description>Compare the efficacy of sacituzumab govitecan with pembrolizumab to that of sacituzumab govitecan alone by assessing Objective Response Rate by RECIST 1.1.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of response (DOR)</measure>
    <time_frame>3 years</time_frame>
    <description>Compare the efficacy of sacituzumab govitecan with pembrolizumab to that of sacituzumab govitecan alone by assessing the duration of response (the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented or death due to any cause. Participants without events reported are censored at the last disease evaluation).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to objective response (TTOR)</measure>
    <time_frame>3 years</time_frame>
    <description>Compare the efficacy of sacituzumab govitecan with pembrolizumab to that of sacituzumab govitecan alone by assessing the time to objective response defined as the time from randomization to the date of the first documented CR or PR (whichever is first recorded).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to progression (TTP)</measure>
    <time_frame>3 years</time_frame>
    <description>Compare the efficacy of sacituzumab govitecan with pembrolizumab to that of sacituzumab govitecan alone by assessing Time to progression (TTP) defined as the time from randomization (or registration) to progression, or censored at date of last disease evaluation for those without progression reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical benefit rate (CBR)</measure>
    <time_frame>3 years</time_frame>
    <description>Compare the efficacy of sacituzumab govitecan with pembrolizumab to that of sacituzumab govitecan alone by assessing Clinical benefit rate (CBR) according to RECIST 1.1, defined as CR, PR or stable disease for ≥ 24 weeks.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants with Treatment-Related Adverse Events as Assessed by CTCAE v5.0</measure>
    <time_frame>3 years</time_frame>
    <description>Evaluate the safety and tolerability of sacituzumab govitecan and pembrolizumab compared to sacituzumab govitecan alone by monitoring adverse events, including immune-related adverse events.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Anticipated">110</enrollment>
  <condition>Breast Cancer</condition>
  <condition>Triple Negative Breast Cancer</condition>
  <condition>PD-L1 Negative</condition>
  <arm_group>
    <arm_group_label>Sacituzumab Govitecan + Pembrolizumab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive Sacituzumab Govitecan + Pembrolizumab at a pre-determined dose during a 21 day cycle.&#xD;
Sacituzumab Govitecan will be given on days 1 and 8 of the 21 day cycle Pembrolizumab will be given on day 1 of the 21 day cycle.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Sacituzumab Govitecan</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive Sacituzumab Govitecan at a pre-determined dose during a 21 day cycle.&#xD;
Sacituzumab Govitecan will be given on days 1 and 8 of a 21-day cycle</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Retreatment</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants randomized to the combination arm (Sacituzumab Govitecan + Pembrolizumab) who stop with CR after at least 24 weeks of treatment may be eligible for additional pembrolizumab and/or sacituzumab govitecan therapy if they progress after stopping study treatment. This is termed the Second Course Phase and is only available if the study remains open and the subject meets conditions.&#xD;
.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Sacituzumab Govitecan</intervention_name>
    <description>Intravenous Infusion</description>
    <arm_group_label>Retreatment</arm_group_label>
    <arm_group_label>Sacituzumab Govitecan</arm_group_label>
    <arm_group_label>Sacituzumab Govitecan + Pembrolizumab</arm_group_label>
    <other_name>IMMU-132</other_name>
    <other_name>Trodelvy</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pembrolizumab</intervention_name>
    <description>Intravenous Infusion</description>
    <arm_group_label>Retreatment</arm_group_label>
    <arm_group_label>Sacituzumab Govitecan + Pembrolizumab</arm_group_label>
    <other_name>Keytruda</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Participants must have histologically or cytologically confirmed invasive breast&#xD;
             cancer with unresectable locally advanced or metastatic disease. Participants without&#xD;
             pathologic or cytologic confirmation of metastatic disease should have unequivocal&#xD;
             evidence of metastasis from physical examination or radiologic evaluation.&#xD;
&#xD;
          -  Estrogen-receptor and progesterone-receptor expression both ≤ 5% by&#xD;
             immunohistochemistry (IHC), and HER2-negative status as determined by the current&#xD;
             ASCO/CAP guidelines. If a patient has more than one histological result, the most&#xD;
             recent sample will be considered for inclusion.&#xD;
&#xD;
          -  Participants must have PD-L1-negative metastatic breast cancer defined as less than 1%&#xD;
             expression of PD-L1 on tumor-infiltrating immune cells (IC) by the PD-L1 IHC SP142&#xD;
             assay or a Combined Positive Score (CPS) less than 10 by the PD-L1 IHC 22C3 assay&#xD;
             measured with standard of care testing.&#xD;
&#xD;
          -  Participants must be treatment-naïve in the metastatic setting.&#xD;
&#xD;
          -  Participants must have evaluable or measurable disease per RECIST 1.1. Patients with&#xD;
             bone only disease will be allowed to participate.&#xD;
&#xD;
          -  Participants must agree to undergo a research biopsy, if tumor is safely accessible,&#xD;
             at baseline. Previously collected archival tissue will also be obtained on all&#xD;
             participants. Tissue needs to be located and availability confirmed at time of&#xD;
             registration (see Section 9 for more details). Participants must agree to a mandatory&#xD;
             repeat biopsy 3-6 weeks after starting treatment, if tumor is safely accessible.&#xD;
&#xD;
          -  Prior chemotherapy: Participants must have received no prior chemotherapy for&#xD;
             metastatic breast cancer and must have discontinued all chemotherapy at least 28 days&#xD;
             prior to study treatment initiation. No prior irinotecan or topoisomerase I-containing&#xD;
             antibody drug conjugates in the metastatic or neo/adjuvant setting are allowed. All&#xD;
             toxicities related to prior chemotherapy must have resolved to CTCAE v5.0 grade 1 or&#xD;
             lower, unless otherwise specified per protocol, except alopecia can be any grade and&#xD;
             neuropathy can be grade 2 or lower.&#xD;
&#xD;
          -  Prior biologic therapy: Patients must have received no prior biologic therapy for&#xD;
             metastatic breast cancer and discontinued all biologic therapy at least 28 days prior&#xD;
             to study treatment initiation. All toxicities related to prior biologic therapy must&#xD;
             have resolved to CTCAE v5.0 grade 1 or lower, unless otherwise specified per protocol.&#xD;
&#xD;
          -  Prior radiation therapy: Patients may have received prior radiation therapy. Radiation&#xD;
             therapy must be completed at least 7 days prior to study treatment initiation, and all&#xD;
             toxicities related to prior radiation therapy must have resolved to CTCAE v5.0 grade 1&#xD;
             or lower, unless otherwise specified per protocol. A 1-week washout is permitted for&#xD;
             palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease.&#xD;
&#xD;
          -  Previously treated brain metastases are permitted, with the following provisions:&#xD;
&#xD;
               -  Prior SRS should complete ≥ 7 days before study treatment initiation&#xD;
&#xD;
               -  Prior WBRT should complete ≥ 7 days before study treatment initiation.&#xD;
&#xD;
               -  Any corticosteroid use for brain metastases must have been discontinued for ≥ 7&#xD;
                  days prior to study treatment initiation.&#xD;
&#xD;
          -  The subject is ≥ 18 years old.&#xD;
&#xD;
          -  ECOG performance status 0-1 (Karnofsky &gt; 60%, see Appendix A).&#xD;
&#xD;
          -  Participants must have normal organ and marrow function as defined below:&#xD;
&#xD;
               -  Absolute neutrophil count ≥1,000/mcL&#xD;
&#xD;
               -  Platelets ≥100,000/mcL&#xD;
&#xD;
               -  Hemoglobin ≥ 9.0 g/dl&#xD;
&#xD;
               -  INR/PT/aPTT ≤1.5 × ULN unless participant is receiving anticoagulant therapy as&#xD;
                  long as PT or aPTT is in therapeutic range of anticoagulant&#xD;
&#xD;
               -  Total bilirubin ≤1.5 × institutional upper limit of normal (ULN)(or ≤2.0 x ULN in&#xD;
                  patients with documented Gilbert's Syndrome)&#xD;
&#xD;
               -  AST(SGOT)/ALT(SGPT) ≤2.5 × institutional ULN or ≤5 × institutional ULN for&#xD;
                  participants with documented liver metastases&#xD;
&#xD;
               -  Serum creatinine ≤1.5 × institutional ULN OR creatinine clearance ≥ 30 mL/min/&#xD;
                  1.73m2 for participants with creatinine levels above institutional ULN.&#xD;
&#xD;
          -  Female subjects of childbearing potential must have a negative serum or urine&#xD;
             pregnancy test within 2 weeks prior to study treatment initiation. Childbearing&#xD;
             potential is defined as participants who have not reached a postmenopausal state (≥ 12&#xD;
             continuous months of amenorrhea with no identified cause other than menopause) and&#xD;
             have not undergone surgical sterilization (removal of ovaries and/or uterus).&#xD;
&#xD;
          -  Women of childbearing potential (WOCBP) must agree to use an adequate method of&#xD;
             contraception. Contraception is required starting with the first dose of study&#xD;
             medication through 180 days (6 months) after the last dose of study medication.&#xD;
             Examples of contraceptive methods with a failure rate of &lt; 1% per year include&#xD;
             bilateral tubal ligation, male sterilization, established and proper use of hormonal&#xD;
             contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and&#xD;
             copper intrauterine devices. Periodic abstinence (e.g., calendar, ovulation,&#xD;
             symptothermal, or postovulation methods) and withdrawal are not acceptable methods of&#xD;
             contraception.&#xD;
&#xD;
          -  Males who are sexually active with WOCBP must agree to follow instructions for&#xD;
             method(s) of contraception for the duration of study treatment with pembrolizumab and&#xD;
             3 months after the last dose of study treatment&#xD;
&#xD;
          -  Participants on bisphosphonates or RANK ligand inhibitors may continue receiving&#xD;
             therapy during study treatment and also may initiate therapy with these agents on&#xD;
             study if clinically indicated.&#xD;
&#xD;
          -  The participant must be capable of understanding and complying with the protocol and&#xD;
             willing to sign a written informed consent document.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Has received prior systemic anti-cancer therapy, including investigational agents,&#xD;
             within 4 weeks of study treatment initiation or during the course of this study&#xD;
             (bisphosphonates and RANK ligand inhibitors are allowed).&#xD;
&#xD;
          -  Prior therapy with any anti-PD-1, PD-L1, or PD-L2 agent or sacituzumab govitecan&#xD;
             (IMMU-132). Prior therapy with irinotecan or topoisomerase I-containing antibody drug&#xD;
             conjugates at any time for early stage or metastatic disease.&#xD;
&#xD;
          -  Prior hypersensitivity to pembrolizumab or the excipients of pembrolizumab or&#xD;
             sacituzumab govitecan (IMMU-132 therapy).&#xD;
&#xD;
          -  Known history of UDP-glucuronosyltransferase 1A1 (UGT1A1) *28 allele homozygosity,&#xD;
             which is associated with increased risk for neutropenia and diarrhea related to&#xD;
             irinotecan. Note: Concurrent administration of strong UGT1A1 inhibitors or inducers is&#xD;
             not allowed during the course of the study.&#xD;
&#xD;
          -  Known brain metastases that are untreated, symptomatic, or require therapy to control&#xD;
             symptoms.&#xD;
&#xD;
          -  Major surgery within 2 weeks prior to study treatment initiation. Patients must have&#xD;
             recovered from any effects of any major surgery.&#xD;
&#xD;
          -  Uncontrolled, significant intercurrent or recent illness including, but not limited&#xD;
             to, ongoing or active infection, uncontrolled non-malignant systemic disease,&#xD;
             uncontrolled seizures, or psychiatric illness/social situation that would limit&#xD;
             compliance with study requirements in the opinion of the treating investigator.&#xD;
&#xD;
          -  Participant has a medical condition that requires chronic systemic steroid therapy (&gt;&#xD;
             10 mg of prednisone daily or equivalent) or any other form of immunosuppressive&#xD;
             medication (including disease modifying agents) and has required such therapy in the&#xD;
             last 2 years. Replacement therapy (e.g. thyroxine, insulin, or physiologic&#xD;
             corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is&#xD;
             not considered a form of systemic therapy.&#xD;
&#xD;
          -  Participant has documented history of autoimmune disease or syndrome that currently&#xD;
             requires systemic steroids or immunosuppressive agents.&#xD;
&#xD;
          -  History of (non-infectious) pneumonitis that required steroids or current pneumonitis.&#xD;
&#xD;
          -  Individuals with a history of a second malignancy are ineligible except for the&#xD;
             following circumstances. Individuals with a history of other malignancies are eligible&#xD;
             if they have been disease-free for at least 3 years or are deemed by the investigator&#xD;
             to be at low risk for recurrence of that malignancy. Individuals with the following&#xD;
             cancers that have been diagnosed and treated within the past 3 years are eligible:&#xD;
             cervical/prostate carcinoma in situ, superficial bladder cancer, non-melanoma cancer&#xD;
             of the skin. Patients with other cancers diagnosed within the past 3 years and felt to&#xD;
             be at low risk of recurrence should be discussed with the study principal investigator&#xD;
             to determine eligibility.&#xD;
&#xD;
          -  Participant has a known history of human immunodeficiency virus (HIV), Hepatitis B&#xD;
             (defined as Hepatitis B surface antigen [HBsAg] reactive) or known active Hepatitis C&#xD;
             virus (defined as detected HCV RNA [qualitative]) infection. HIV-positive participants&#xD;
             are ineligible due to the potential for pharmacokinetic interactions of combination&#xD;
             antiretroviral therapy with study drugs and the increased risk of fatal infections&#xD;
             when treated with marrow-suppressive therapy. Note: No testing for HIV, Hepatitis B,&#xD;
             or Hepatitis C is required unless mandated by local health authority.&#xD;
&#xD;
          -  The participant has received a live vaccine within 28 days prior to study treatment&#xD;
             initiation. Examples of live vaccines include, but are not limited to, the following:&#xD;
             measles, mumps, rubella, varicella/zoster, yellow fever, rabies, BCG, and typhoid&#xD;
             vaccine. The use of the inactivated seasonal influenza vaccine is allowed.&#xD;
&#xD;
          -  Has a history or current evidence of any condition, therapy, or laboratory abnormality&#xD;
             that might confound the results of the study, interfere with the subject's&#xD;
             participation for the full duration of the study, or is not in the best interest of&#xD;
             the subject to participate, in the opinion of the treating investigator.&#xD;
&#xD;
          -  It is unknown whether pembrolizumab is excreted in human milk. Since many drugs are&#xD;
             excreted in human milk, and because of the potential for serious adverse reactions in&#xD;
             the nursing infant, participants who are breast-feeding are not eligible for&#xD;
             enrollment.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ana C Garrido-Castro, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Dana-Farber Cancer Institute</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Ana C Garrido-Castro, MD</last_name>
    <phone>617-632-6409</phone>
    <email>Ana_Garrido-Castro@dfci.harvard.edu</email>
  </overall_contact>
  <location>
    <facility>
      <name>Stamford Hospital</name>
      <address>
        <city>Stamford</city>
        <state>Connecticut</state>
        <zip>06904</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>K.M. Steve Lo, MD</last_name>
      <email>slo@stamhealth.org</email>
    </contact>
    <investigator>
      <last_name>K.M. Steve Lo, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>University of Chicago Medical Center</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60637</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Rita Nanda, MD</last_name>
      <email>rnanda@medicine.bsd.uchicago.edu</email>
    </contact>
    <investigator>
      <last_name>Rita Nanda, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Eastern Maine Medical Center</name>
      <address>
        <city>Brewer</city>
        <state>Maine</state>
        <zip>04412</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Sarah Sinclair, DO</last_name>
      <email>ssinclair@emhs.org</email>
    </contact>
    <investigator>
      <last_name>Sarah Sinclair, DO</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Dana Farber Cancer Institute</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02215</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Ana C. Garrido-Castro, MD</last_name>
      <phone>617-632-6409</phone>
      <email>Ana_Garrido-Castro@dfci.harvard.edu</email>
    </contact>
    <investigator>
      <last_name>Ana C. Garrido-Castro, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>DFCI @ Foxborough</name>
      <address>
        <city>Foxboro</city>
        <state>Massachusetts</state>
        <zip>02035</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Natalie Sinclair, MD</last_name>
      <email>Nsinclair1@partners.org</email>
    </contact>
    <investigator>
      <last_name>Natalie Sinclair, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>DFCI @ Milford Regional Hospital</name>
      <address>
        <city>Milford</city>
        <state>Massachusetts</state>
        <zip>01757</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Natalie Sinclair, MD</last_name>
      <email>nsinclair1@partners.org</email>
    </contact>
    <investigator>
      <last_name>Natalie Sinclair, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>DF/BWCC in Clinical Affiliation with South Shore Hospital</name>
      <address>
        <city>South Weymouth</city>
        <state>Massachusetts</state>
        <zip>02190</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Thomas P O'Connor, MD</last_name>
      <email>ThomasP_O'Connor@DFCI.HARVARD.EDU</email>
    </contact>
    <investigator>
      <last_name>Thomas P O'Connor, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>The University of North Carolina at Chapel Hill</name>
      <address>
        <city>Chapel Hill</city>
        <state>North Carolina</state>
        <zip>27599</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Emily Ray, MD</last_name>
      <email>emmi@ad.unc.edu</email>
    </contact>
    <investigator>
      <last_name>Emily Ray, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>University of Pennsylvania-Abramson Cancer Center</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19104</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Payal Shah, MD</last_name>
      <email>payal.shah@pennmedicine.upenn.edu</email>
    </contact>
    <investigator>
      <last_name>Payal Shah, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Sarah Cannon Research Institute</name>
      <address>
        <city>Chattanooga</city>
        <state>Tennessee</state>
        <zip>37404</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Brooke R Daniel, MD</last_name>
      <email>bdaniel@tnonc.com</email>
    </contact>
    <investigator>
      <last_name>Brooke R Daniel, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>July 8, 2020</study_first_submitted>
  <study_first_submitted_qc>July 8, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 13, 2020</study_first_posted>
  <last_update_submitted>August 10, 2023</last_update_submitted>
  <last_update_submitted_qc>August 10, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 14, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Dana-Farber Cancer Institute</investigator_affiliation>
    <investigator_full_name>Ana C Garrido-Castro, MD</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>Breast Cancer</keyword>
  <keyword>Triple Negative Breast Cancer</keyword>
  <keyword>PD-L1 Negative</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Breast Neoplasms</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>Pembrolizumab</mesh_term>
    <mesh_term>Sacituzumab govitecan</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: [contact information for Sponsor Investigator or designee]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.</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_time_frame>Data can be shared no earlier than 1 year following the date of publication.</ipd_time_frame>
    <ipd_access_criteria>Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu</ipd_access_criteria>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</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/NCT04468061
org study id: 20-166
nct id: NCT04468061
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This research study involves testing the safety and efficacy of an investigational
      intervention for patients with triple-negative breast cancer (TNBC) that has spread, or
      metastasized, to other parts the body and is PD-L1-negative.

      The names of the study interventions involved in this study are:

        -  Sacituzumab govitecan (Trodelvy™;IMMU-132)

        -  Pembrolizumab (Keytruda®; MK-3475)
This research study is a Phase II clinical trial. Phase II clinical trials test the safety
      and effectiveness of an investigational drug or a combination of investigational drugs to
      learn whether the drug or drug combination works in treating a specific disease.
      "Investigational" means that the drug or drug combination is being studied.

      The U.S. Food and Drug Administration (FDA) has approved Sacituzumab Govitecan for metastatic
      triple-negative breast cancer, but it is currently approved only for patients who have had 2
      or more prior regimens for metastatic disease. The U.S. Food and Drug Administration (FDA)
      has approved Pembrolizumab for metastatic triple-negative breast cancer, but it is currently
      approved only for patients with PD-L1-positive metastatic triple-negative breast cancer.

      In this research study, we are:

        -  Studying Sacituzumab Govitecan alone or in combination with Pembrolizumab as a possible
           treatment for patients with metastatic triple-negative breast cancers that are
           PD-L1-negative.

        -  Sacituzumab Govitecan is composed of a chemotherapy drug, called Irinotecan, which is
           attached to an antibody. Antibodies are proteins normally made by the immune system that
           bind to substances that don't belong in the body to prevent harm. The antibody in this
           study binds to certain types of cancer tumors, including triple-negative breast tumors.

        -  Pembrolizumab is an immunotherapy, called an anti-PD-1 or a checkpoint inhibitor, and is
           an antibody (a type of human protein) designed to allow the body's own immune system to
           seek out and destroy tumors. It has been used in previous research studies to treat
           breast cancer, where it has been shown to be effective.

        -  The overall goal of this study is to evaluate the effectiveness of either Sacituzumab
           Govitecan alone or in combination with Pembrolizumab, in delaying the worsening of
           triple-negative breast cancers that are PD-L1-negative.

      The research study procedures include: screening for eligibility, research blood collections,
      at least two research biopsies, paired research stool collections, questionnaires, data
      collection, and study treatment including evaluations and follow up visits.

      Participants will be randomized into one of two groups.

        -  Group A: Sacituzumab Govitecan on days 1 and 8 and Pembrolizumab on day 1 of a 21-day
           cycle

        -  Group B: Sacituzumab Govitecan alone on days 1 and 8 of a 21-day cycle

      Participants will receive study treatment for as long as they are benefitting from this
      therapy. Participants will be followed for the rest of their life.

      It is expected that about 110 people will take part in this research study.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Progression Free Survival (PFS)
time frame: 3 years
description: Compare PFS of patients randomized to receive sacituzumab govitecan in combination with pembrolizumab (Arm A) versus those randomized to receive sacituzumab govitecan monotherapy (Arm B).
Defined as the time from study randomization to disease progression, per RECIST 1.1 or medical judgment, the latter based on established clinical parameters, such as rising tumor markers and physical exam evidence of progression, i.e. worsening chest wall disease, or death due to any cause, whichever occurred first.
measure: Overall Survival (OS)
time frame: 3 years
description: Compare the efficacy of sacituzumab govitecan with pembrolizumab to that of sacituzumab govitecan alone by assessing Overall Survival (OS), defined as the time from randomization (or registration) to death due to any cause, or censored at date last known alive, will be reported with Kaplan Meier estimates.
measure: Objective Response Rate (ORR)
time frame: 3 years
description: Compare the efficacy of sacituzumab govitecan with pembrolizumab to that of sacituzumab govitecan alone by assessing Objective Response Rate by RECIST 1.1.
measure: Duration of response (DOR)
time frame: 3 years
description: Compare the efficacy of sacituzumab govitecan with pembrolizumab to that of sacituzumab govitecan alone by assessing the duration of response (the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented or death due to any cause. Participants without events reported are censored at the last disease evaluation).
measure: Time to objective response (TTOR)
time frame: 3 years
description: Compare the efficacy of sacituzumab govitecan with pembrolizumab to that of sacituzumab govitecan alone by assessing the time to objective response defined as the time from randomization to the date of the first documented CR or PR (whichever is first recorded).
measure: Time to progression (TTP)
time frame: 3 years
description: Compare the efficacy of sacituzumab govitecan with pembrolizumab to that of sacituzumab govitecan alone by assessing Time to progression (TTP) defined as the time from randomization (or registration) to progression, or censored at date of last disease evaluation for those without progression reported.
measure: Clinical benefit rate (CBR)
time frame: 3 years
description: Compare the efficacy of sacituzumab govitecan with pembrolizumab to that of sacituzumab govitecan alone by assessing Clinical benefit rate (CBR) according to RECIST 1.1, defined as CR, PR or stable disease for ≥ 24 weeks.
measure: Number of Participants with Treatment-Related Adverse Events as Assessed by CTCAE v5.0
time frame: 3 years
description: Evaluate the safety and tolerability of sacituzumab govitecan and pembrolizumab compared to sacituzumab govitecan alone by monitoring adverse events, including immune-related adverse events.
arm group label: Sacituzumab Govitecan + Pembrolizumab
arm group type: Experimental
description: Participants will receive Sacituzumab Govitecan + Pembrolizumab at a pre-determined dose during a 21 day cycle.
Sacituzumab Govitecan will be given on days 1 and 8 of the 21 day cycle Pembrolizumab will be given on day 1 of the 21 day cycle.
arm group label: Sacituzumab Govitecan
arm group type: Experimental
description: Participants will receive Sacituzumab Govitecan at a pre-determined dose during a 21 day cycle.
Sacituzumab Govitecan will be given on days 1 and 8 of a 21-day cycle
arm group label: Retreatment
arm group type: Experimental
description: Participants randomized to the combination arm (Sacituzumab Govitecan + Pembrolizumab) who stop with CR after at least 24 weeks of treatment may be eligible for additional pembrolizumab and/or sacituzumab govitecan therapy if they progress after stopping study treatment. This is termed the Second Course Phase and is only available if the study remains open and the subject meets conditions.
.
intervention type: Drug
intervention name: Sacituzumab Govitecan
description: Intravenous Infusion
arm group label: Retreatment
arm group label: Sacituzumab Govitecan
arm group label: Sacituzumab Govitecan + Pembrolizumab
other name: IMMU-132
other name: Trodelvy
intervention type: Drug
intervention name: Pembrolizumab
description: Intravenous Infusion
arm group label: Retreatment
arm group label: Sacituzumab Govitecan + Pembrolizumab
other name: Keytruda
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Ana C Garrido-Castro, MD
role: Principal Investigator
affiliation: Dana-Farber Cancer Institute
last name: Ana C Garrido-Castro, MD
phone: 617-632-6409
email: Ana_Garrido-Castro@dfci.harvard.edu
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Dana-Farber Cancer Institute
investigator full name: Ana C Garrido-Castro, MD
investigator title: Principal Investigator
mesh term: Breast Neoplasms
mesh term: Triple Negative Breast Neoplasms
mesh term: Pembrolizumab
mesh term: Sacituzumab govitecan
sharing ipd: Yes
ipd description: The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: [contact information for Sponsor Investigator or designee]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Informed Consent Form (ICF)
ipd time frame: Data can be shared no earlier than 1 year following the date of publication.
ipd access criteria: Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu