<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/NCT04445844</url>
  </required_header>
  <id_info>
    <org_study_id>042001</org_study_id>
    <secondary_id>NCI-2020-02940</secondary_id>
    <secondary_id>Pro2020000268</secondary_id>
    <secondary_id>Pro2020000268</secondary_id>
    <secondary_id>P30CA072720</secondary_id>
    <nct_id>NCT04445844</nct_id>
  </id_info>
  <brief_title>INCMGA00012 and Pelareorep for the Treatment of Metastatic Triple Negative Breast Cancer, IRENE Study</brief_title>
  <official_title>IRENE Study: Phase 2 Study of INCMGA00012 and the Oncolytic Virus Pelareorep in Metastatic Triple Negative Breast Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Rutgers, The State University of New Jersey</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Incyte Corporation</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Oncolytics Biotech</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>Rutgers, The State University of New Jersey</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 is a phase 2 study to evaluate the safety and efficacy of the combination of INCMGA00012&#xD;
      and pelareorep and to see how well they work in treating patients with triple negative breast&#xD;
      cancer that has spread to other parts of the body (metastatic).&#xD;
&#xD;
      INCMGA00012 is a monoclonal antibody that works by attaching to the programmed cell death&#xD;
      protein 1 (PD-1) and blocking this pathway, allowing the immune system to recognize and&#xD;
      attack the cancer cells. Pelareorep is a type of virus called reovirus which occurs naturally&#xD;
      and may break down cancer cells. Giving INCMGA00012 and pelareorep may slow the growth and&#xD;
      spread of the cancer to another part of the body.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVES:&#xD;
&#xD;
      I. To determine the efficacy of the combination of retifanlimab (INCMGA00012) and pelareorep&#xD;
      for patients with metastatic triple negative breast cancer in the second and third line&#xD;
      setting.&#xD;
&#xD;
      II. To assess the safety, tolerability and feasibility of INCMGA00012 in combination with the&#xD;
      oncolytic virus pelareorep for patients with metastatic triple negative breast cancer in the&#xD;
      second and third line setting.&#xD;
&#xD;
      SECONDARY OBJECTIVES:&#xD;
&#xD;
      I. To assess progression free survival (PFS), overall survival (OS) and duration of response&#xD;
      (DOR) in patients receiving INCMGA00012 in combination with the oncolytic virus pelareorep&#xD;
      for patients with metastatic triple negative breast cancer in the second and third line&#xD;
      setting.&#xD;
&#xD;
      II. To assess quality of life measures.&#xD;
&#xD;
      EXPLORATORY OBJECTIVES:&#xD;
&#xD;
      I. To assess whether pre-treatment PD-L1 expression is associated with treatment outcomes.&#xD;
&#xD;
      II. To determine if changes in T cell repertoire as measured by T-cell receptor (TCR)&#xD;
      sequencing is predictive of treatment outcomes.&#xD;
&#xD;
      OUTLINE:&#xD;
&#xD;
      Patients receive pelareorep intravenously (IV) over 60 minutes on days 1, 2, 15, and 16.&#xD;
      Patients also receive retifanlimab IV over 60 minutes on day 3. Cycles repeat every 28 days&#xD;
      in the absence of disease progression or unacceptable toxicity.&#xD;
&#xD;
      After completion of study treatment, patients are followed up at 30 and 90 days, then every 6&#xD;
      months for up to 2 years.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">July 13, 2020</start_date>
  <completion_date type="Anticipated">September 30, 2023</completion_date>
  <primary_completion_date type="Anticipated">June 30, 2023</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Objective response rate (ORR)</measure>
    <time_frame>Within 8 weeks after completion of treatment</time_frame>
    <description>Defined as the percentage of participants having an objective response (complete response [CR] or partial response [PR]), according to Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1. The ORR of the drug will be assessed according to Simon's two stage design. The estimated ORR will be compared to the response rate specified in the null hypothesis (6%) using one-sided exact binomial test at type I error 5%. 95% confidence interval (C.I.) will be also reported.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of adverse events</measure>
    <time_frame>Up to 2 years after completion of treatment</time_frame>
    <description>Will be determined by the number, frequency, duration, and severity of adverse events (AEs) using Common Terminology Criteria for Adverse Events (CTCAE) v 5.0; laboratory tests and vital signs.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Progression free survival (PFS)</measure>
    <time_frame>From the start of therapy until disease progression, or death due to any cause, assessed up to 2 years after completion of treatment</time_frame>
    <description>Will be determined by the immune complete response (iCR). Will be estimated using Kaplan-Meier product-limit method. The median PFS times with two-sided 95% CIs will be estimated.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival (OS)</measure>
    <time_frame>From the start of therapy until death due to any cause, assessed up to 2 years after completion of treatment</time_frame>
    <description>Will be estimated using Kaplan-Meier product-limit method. The median OS times with two-sided 95% CIs will be estimated.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Response (DOR)</measure>
    <time_frame>Up to 2 years after completion of treatment</time_frame>
    <description>Defined as the time from an initial objective response (CR or PR) according to RECIST v 1.1 until disease progression, or death due to any cause, as determined by iCR.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of life will be evaluated by European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ)-Core 30 (C30).</measure>
    <time_frame>Up to 2 years after completion of treatment</time_frame>
  </secondary_outcome>
  <other_outcome>
    <measure>Changes in PD-L1 expression</measure>
    <time_frame>Pre and post-treatment</time_frame>
    <description>Will be correlated with treatment response.</description>
  </other_outcome>
  <other_outcome>
    <measure>T-cell receptor (TCR) sequencing</measure>
    <time_frame>Up to 2 years after completion of treatment</time_frame>
    <description>Assess the role of TCR sequencing in predicting treatment response.</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">25</enrollment>
  <condition>Anatomic Stage IV Breast Cancer AJCC v8</condition>
  <condition>Locally Advanced Breast Carcinoma</condition>
  <condition>Metastatic Triple-Negative Breast Carcinoma</condition>
  <condition>Prognostic Stage IV Breast Cancer AJCC v8</condition>
  <condition>Triple-negative Breast Cancer</condition>
  <arm_group>
    <arm_group_label>Treatment (pelareorep, retifanlimab)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receive pelareorep IV over 60 minutes on days 1, 2, 15, and 16. Patients also receive INCMGA00012 IV over 60 minutes on day 3. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Pelareorep</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Treatment (pelareorep, retifanlimab)</arm_group_label>
    <other_name>PO BB0209</other_name>
    <other_name>PO-BB0209</other_name>
    <other_name>Reolysin</other_name>
    <other_name>Reovirus Serotype 3</other_name>
    <other_name>Wild-type Reovirus</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Quality-of-Life Assessment</intervention_name>
    <description>Ancillary studies</description>
    <arm_group_label>Treatment (pelareorep, retifanlimab)</arm_group_label>
    <other_name>Quality of Life Assessment</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Questionnaire Administration</intervention_name>
    <description>Ancillary studies</description>
    <arm_group_label>Treatment (pelareorep, retifanlimab)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Retifanlimab</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Treatment (pelareorep, retifanlimab)</arm_group_label>
    <other_name>INCMGA 0012</other_name>
    <other_name>INCMGA-0012</other_name>
    <other_name>INCMGA00012</other_name>
    <other_name>INCMGA0012</other_name>
    <other_name>MGA 012</other_name>
    <other_name>MGA-012</other_name>
    <other_name>MGA012</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Metastatic or inoperable locally advanced, histologically documented triple negative&#xD;
             breast cancer (TNBC) (negative expression of estrogen receptor [ER], progesterone&#xD;
             receptor [PR] and human epidermal growth factor receptor 2 [HER2] immunohistochemistry&#xD;
             [IHC] 0 or 1+, HER2 fluorescence in situ hybridization [FISH] negative if IHC 2+, per&#xD;
             American Society of Clinical Oncology [ASCO] College of American Pathologists [CAP]&#xD;
             guidelines)&#xD;
&#xD;
          -  Pre-menopausal and post-menopausal women who have received 1-2 prior lines of systemic&#xD;
             therapy for metastatic triple negative breast cancer. Patients must have received at&#xD;
             least one prior line of chemotherapy&#xD;
&#xD;
          -  Patients who have received adjuvant therapy for locally advanced triple negative&#xD;
             breast cancer may be eligible for the study if they relapse with metastatic disease&#xD;
             within 6 months since completion of neo-adjuvant/adjuvant systemic therapy. The&#xD;
             adjuvant/neoadjuvant therapy will be considered as 1 line of therapy&#xD;
&#xD;
          -  Availability of tumor specimen for determination of PD-L1 and additional biomarker&#xD;
             studies. Patient should be willing to undergo a pre-treatment biopsy as well as a&#xD;
             biopsy after cycle 2 to evaluate the tumor microenvironment&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2&#xD;
&#xD;
          -  Patients who have received prior treatment with anti-PD-1 or anti-PD-L1 inhibitors are&#xD;
             eligible for the study&#xD;
&#xD;
          -  Absolute neutrophil count &gt;= 1,000/uL&#xD;
&#xD;
          -  Platelet count &gt;= 100,000/uL&#xD;
&#xD;
          -  Hemoglobin &gt;= 9.0 g/dL&#xD;
&#xD;
          -  Total bilirubin =&lt; 2 x upper limit of normal (ULN) or =&lt; 3 x ULN for subjects with&#xD;
             Gilbert's disease or liver metastases&#xD;
&#xD;
          -  Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =&lt; 3 x ULN (=&lt; 5 x&#xD;
             ULN if evidence of hepatic involvement by malignant disease)&#xD;
&#xD;
          -  Estimated glomerular filtration rate (eGFR) &gt;= 40 mL/min/1.73m^2&#xD;
&#xD;
          -  Lactate dehydrogenase (LDH) &lt; 2 x ULN&#xD;
&#xD;
          -  Provision of signed and dated informed consent form&#xD;
&#xD;
          -  Life expectancy &gt;= 3 months, as determined by the investigator&#xD;
&#xD;
          -  Patients must have clinically and/or radiographically documented measurable disease.&#xD;
             At least one site of disease must be uni-dimensionally measurable as per Response&#xD;
             Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1&#xD;
&#xD;
          -  For patients receiving therapeutic anticoagulation: stable anticoagulant regimen&#xD;
             during the 14 days prior to initiation of study treatment&#xD;
&#xD;
          -  Subjects with central nervous system (CNS) metastases treated with radiation therapy&#xD;
             (whole-brain radiation therapy [WBXRT] or stereotactic radiosurgery [SRS]) are&#xD;
             eligible if, &gt; 28 days following completion of radiation therapy (XRT), they show&#xD;
             stable disease on post-treatment magnetic resonance imaging (MRI)/computed tomography&#xD;
             (CT), are off corticosteroids, and are neurologically stable&#xD;
&#xD;
          -  Female patients of childbearing potential have a negative pregnancy test at baseline.&#xD;
             Females of childbearing potential are defined as sexually mature women without prior&#xD;
             hysterectomy or who have had any evidence of menses in the past 12 months. However,&#xD;
             women who have been amenorrheic for 12 or more months are still considered to be of&#xD;
             childbearing potential if the amenorrhea is possibly due to prior chemotherapy, anti&#xD;
             estrogens, or ovarian suppression&#xD;
&#xD;
               -  Patients who are not postmenopausal (&gt;= 12 months of non-therapy-induced&#xD;
                  amenorrhea) or surgically sterile must have a negative urine pregnancy test&#xD;
                  (positive urine tests are to be confirmed by serum test) documented within 14&#xD;
                  days of treatment initiation&#xD;
&#xD;
               -  Sexually active women of childbearing potential enrolled in the study must agree&#xD;
                  to use 2 forms of accepted methods of contraception during the course of the&#xD;
                  study and for 12 weeks after their last dose of study drug. Effective birth&#xD;
                  control includes (a) intrauterine device plus 1 barrier method; (b) on stable&#xD;
                  doses of hormonal contraception for at least 3 months (e.g., oral, injectable,&#xD;
                  implant, transdermal) plus one barrier method; (c) 2 barrier methods. Effective&#xD;
                  barrier methods are male or female condoms, diaphragms, and spermicides (creams&#xD;
                  or gels that contain a chemical to kill sperm); or (d) a vasectomized partner&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Subjects who have received 4 or more lines prior treatment in the metastatic setting&#xD;
&#xD;
          -  Has active autoimmune disease that has required systemic treatment in the past 2 years&#xD;
             (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive&#xD;
             drugs) or a documented history of clinically severe autoimmune disease, or a syndrome&#xD;
             that requires systemic steroids or immunosuppressive agents. Vitiligo, alopecia,&#xD;
             hypothyroidism only requiring hormone replacement, psoriasis not requiring systemic&#xD;
             treatment, celiac disease controlled by diet alone or conditions not expected to recur&#xD;
             in the absence of an external trigger are permitted&#xD;
&#xD;
          -  History of psychiatric illness or social situations that would limit compliance with&#xD;
             study requirements. Has a history or current evidence of any condition, therapy, or&#xD;
             laboratory abnormality that might confound the results of the trial, interfere with&#xD;
             the subject's participation for the full duration of the trial, or is not in the best&#xD;
             interest of the subject to participate, in the opinion of the treating investigator&#xD;
&#xD;
          -  Known active, untreated central nervous system (CNS) metastases and/or carcinomatous&#xD;
             meningitis except for patients with =&lt; 3 small (&lt; 0.6 cm) asymptomatic brain lesions&#xD;
             where treatment is not indicated. Patients with neurological symptoms must undergo a&#xD;
             head computed tomography (CT) scan or brain magnetic resonance imaging (MRI) to&#xD;
             exclude brain metastasis&#xD;
&#xD;
          -  Subjects previously treated with pelareorep&#xD;
&#xD;
          -  Evidence of interstitial lung disease, history of interstitial lung disease, or&#xD;
             active, noninfectious pneumonitis&#xD;
&#xD;
          -  Prior allogeneic stem cell or solid organ transplantation&#xD;
&#xD;
          -  Patients may not have non-oncology vaccine therapies for prevention of infectious&#xD;
             disease (for example, seasonal live influenza vaccine, human papilloma virus vaccine)&#xD;
             within 4 weeks of study drug administration. Vaccination while on study is also&#xD;
             prohibited except for administration of the inactivated influenza vaccine&#xD;
&#xD;
          -  Known history of human immunodeficiency virus (HIV) or other serious immunocompromised&#xD;
             state&#xD;
&#xD;
          -  Known positive hepatitis B surface antigen undergoing anti-viral treatment and/or&#xD;
             active hepatitis C indicated by positive quantitative hepatitis C virus (HCV)&#xD;
             ribonucleic acid (RNA)&#xD;
&#xD;
          -  Patient is pregnant or breastfeeding&#xD;
&#xD;
          -  Receipt of any investigational treatment or anti-cancer therapy within 14 days of&#xD;
             enrollment into the study&#xD;
&#xD;
          -  Known hypersensitivity to the study drugs or their components&#xD;
&#xD;
          -  Documented history of a cerebral vascular event (stroke or transient ischemic attack),&#xD;
             unstable angina, myocardial infarction, or cardiac symptoms consistent with New York&#xD;
             Heart Association (NYHA) class III-IV within 6 months prior to their first dose of&#xD;
             study drugs&#xD;
&#xD;
          -  Prior malignancies (except non-melanoma skin cancers, and the following in situ&#xD;
             cancers: bladder, gastric, colon, endometrial, cervical/dysplasia, melanoma, or&#xD;
             breast) unless a complete remission was achieved at least 1 year prior to study entry&#xD;
&#xD;
          -  Active alcohol or drug abuse per treating physician&#xD;
&#xD;
          -  Patients may not participate in any other therapeutic clinical trials, including those&#xD;
             with other investigational agents not included in this trial, throughout the duration&#xD;
             of this study&#xD;
&#xD;
          -  Toxicity of prior therapy that has not recovered to =&lt; grade 1 or baseline (with the&#xD;
             exception of any grade of alopecia and anemia not requiring transfusion support)&#xD;
&#xD;
          -  For patients who have received prior immune-checkpoint therapy: Immune-related&#xD;
             toxicity during prior checkpoint inhibitor therapy for which permanent discontinuation&#xD;
             of therapy was recommended (per product label or consensus guidelines), OR any&#xD;
             immune-related toxicity that required intensive or prolonged immunosuppression. (With&#xD;
             the exception of endocrinopathy that is well controlled on replacement hormones)&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Mridula A George</last_name>
    <role>Principal Investigator</role>
    <affiliation>Rutgers Cancer Institute of New Jersey</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Rutgers Cancer Institute of New Jersey</name>
      <address>
        <city>New Brunswick</city>
        <state>New Jersey</state>
        <zip>08903</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Mridula A. George</last_name>
      <phone>732-235-2465</phone>
      <email>mridula@cinj.rutgers.edu</email>
    </contact>
    <investigator>
      <last_name>Mridula A. George</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>The Ohio State University Stefanie Spielman Comprehensive Breast Center</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <zip>43212</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Nicole Williams, MD</last_name>
      <phone>614-293-0066</phone>
      <email>nicole.williams@osumc.edu</email>
    </contact>
    <investigator>
      <last_name>Nicole Williams, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>February 2023</verification_date>
  <study_first_submitted>June 22, 2020</study_first_submitted>
  <study_first_submitted_qc>June 23, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 24, 2020</study_first_posted>
  <last_update_submitted>February 21, 2023</last_update_submitted>
  <last_update_submitted_qc>February 21, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">February 22, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Rutgers Cancer Institute of New Jersey</investigator_affiliation>
    <investigator_full_name>Mridula George, MD</investigator_full_name>
    <investigator_title>Assistant Professor of Medicine - Medical Oncology</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carcinoma</mesh_term>
    <mesh_term>Breast Neoplasms</mesh_term>
    <mesh_term>Triple Negative Breast Neoplasms</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
  </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/NCT04445844
org study id: 042001
secondary id: NCI-2020-02940
secondary id: Pro2020000268
secondary id: Pro2020000268
secondary id: P30CA072720
nct id: NCT04445844
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This is a phase 2 study to evaluate the safety and efficacy of the combination of INCMGA00012
      and pelareorep and to see how well they work in treating patients with triple negative breast
      cancer that has spread to other parts of the body (metastatic).

      INCMGA00012 is a monoclonal antibody that works by attaching to the programmed cell death
      protein 1 (PD-1) and blocking this pathway, allowing the immune system to recognize and
      attack the cancer cells. Pelareorep is a type of virus called reovirus which occurs naturally
      and may break down cancer cells. Giving INCMGA00012 and pelareorep may slow the growth and
      spread of the cancer to another part of the body.
PRIMARY OBJECTIVES:

      I. To determine the efficacy of the combination of retifanlimab (INCMGA00012) and pelareorep
      for patients with metastatic triple negative breast cancer in the second and third line
      setting.

      II. To assess the safety, tolerability and feasibility of INCMGA00012 in combination with the
      oncolytic virus pelareorep for patients with metastatic triple negative breast cancer in the
      second and third line setting.

      SECONDARY OBJECTIVES:

      I. To assess progression free survival (PFS), overall survival (OS) and duration of response
      (DOR) in patients receiving INCMGA00012 in combination with the oncolytic virus pelareorep
      for patients with metastatic triple negative breast cancer in the second and third line
      setting.

      II. To assess quality of life measures.

      EXPLORATORY OBJECTIVES:

      I. To assess whether pre-treatment PD-L1 expression is associated with treatment outcomes.

      II. To determine if changes in T cell repertoire as measured by T-cell receptor (TCR)
      sequencing is predictive of treatment outcomes.

      OUTLINE:

      Patients receive pelareorep intravenously (IV) over 60 minutes on days 1, 2, 15, and 16.
      Patients also receive retifanlimab IV over 60 minutes on day 3. Cycles repeat every 28 days
      in the absence of disease progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up at 30 and 90 days, then every 6
      months for up to 2 years.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Objective response rate (ORR)
time frame: Within 8 weeks after completion of treatment
description: Defined as the percentage of participants having an objective response (complete response [CR] or partial response [PR]), according to Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1. The ORR of the drug will be assessed according to Simon's two stage design. The estimated ORR will be compared to the response rate specified in the null hypothesis (6%) using one-sided exact binomial test at type I error 5%. 95% confidence interval (C.I.) will be also reported.
measure: Incidence of adverse events
time frame: Up to 2 years after completion of treatment
description: Will be determined by the number, frequency, duration, and severity of adverse events (AEs) using Common Terminology Criteria for Adverse Events (CTCAE) v 5.0; laboratory tests and vital signs.
measure: Progression free survival (PFS)
time frame: From the start of therapy until disease progression, or death due to any cause, assessed up to 2 years after completion of treatment
description: Will be determined by the immune complete response (iCR). Will be estimated using Kaplan-Meier product-limit method. The median PFS times with two-sided 95% CIs will be estimated.
measure: Overall survival (OS)
time frame: From the start of therapy until death due to any cause, assessed up to 2 years after completion of treatment
description: Will be estimated using Kaplan-Meier product-limit method. The median OS times with two-sided 95% CIs will be estimated.
measure: Duration of Response (DOR)
time frame: Up to 2 years after completion of treatment
description: Defined as the time from an initial objective response (CR or PR) according to RECIST v 1.1 until disease progression, or death due to any cause, as determined by iCR.
measure: Quality of life will be evaluated by European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ)-Core 30 (C30).
time frame: Up to 2 years after completion of treatment
measure: Changes in PD-L1 expression
time frame: Pre and post-treatment
description: Will be correlated with treatment response.
measure: T-cell receptor (TCR) sequencing
time frame: Up to 2 years after completion of treatment
description: Assess the role of TCR sequencing in predicting treatment response.
arm group label: Treatment (pelareorep, retifanlimab)
arm group type: Experimental
description: Patients receive pelareorep IV over 60 minutes on days 1, 2, 15, and 16. Patients also receive INCMGA00012 IV over 60 minutes on day 3. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
intervention type: Biological
intervention name: Pelareorep
description: Given IV
arm group label: Treatment (pelareorep, retifanlimab)
other name: PO BB0209
other name: PO-BB0209
other name: Reolysin
other name: Reovirus Serotype 3
other name: Wild-type Reovirus
intervention type: Other
intervention name: Quality-of-Life Assessment
description: Ancillary studies
arm group label: Treatment (pelareorep, retifanlimab)
other name: Quality of Life Assessment
intervention type: Other
intervention name: Questionnaire Administration
description: Ancillary studies
arm group label: Treatment (pelareorep, retifanlimab)
intervention type: Biological
intervention name: Retifanlimab
description: Given IV
arm group label: Treatment (pelareorep, retifanlimab)
other name: INCMGA 0012
other name: INCMGA-0012
other name: INCMGA00012
other name: INCMGA0012
other name: MGA 012
other name: MGA-012
other name: MGA012
criteria: 
gender: Female
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Mridula A George
role: Principal Investigator
affiliation: Rutgers Cancer Institute of New Jersey
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Rutgers Cancer Institute of New Jersey
investigator full name: Mridula George, MD
investigator title: Assistant Professor of Medicine - Medical Oncology
mesh term: Carcinoma
mesh term: Breast Neoplasms
mesh term: Triple Negative Breast Neoplasms
sharing ipd: Yes