<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/NCT04486352</url>
  </required_header>
  <id_info>
    <org_study_id>AFT-50</org_study_id>
    <nct_id>NCT04486352</nct_id>
  </id_info>
  <brief_title>A Study of Targeted Agents for Patients With Recurrent or Persistent Endometrial Cancer</brief_title>
  <acronym>EndoMAP</acronym>
  <official_title>A Phase IB/II Multi-Cohort Study of Targeted Agents and/or Immunotherapy With Atezolizumab for Patients With Recurrent or Persistent Endometrial Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Alliance Foundation Trials, LLC.</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Genentech, Inc.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Foundation Medicine</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Pfizer</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Alliance Foundation Trials, LLC.</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 IB/II multi-cohort study designed to evaluate the efficacy and safety of&#xD;
      targeted agents with or without cancer immune checkpoint therapy with atezolizumab in&#xD;
      participant with recurrent and/or persistent endometrial cancer. The main protocol provides a&#xD;
      platform for genomic screening with homogeneous basic eligibility criteria in order to direct&#xD;
      study participants into biomarker-matched study cohorts consisting of testing targeted&#xD;
      agents.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a Phase IB/II multi-cohort study designed to evaluate the efficacy and safety of&#xD;
      targeted agents with or without cancer immune checkpoint therapy with atezolizumab in&#xD;
      participants with recurrent and/or persistent endometrial cancer.&#xD;
&#xD;
      This biomarker-driven study provides a platform whereby participants with&#xD;
      persistent/recurrent endometrial cancer will be placed into study cohorts evaluating targeted&#xD;
      agents selected on the basis of the tumor's specific genomic profile. Prospective&#xD;
      participants with persistent and/or recurrent endometrial cancer will be prescreened within&#xD;
      60 days of treatment assignment to have a tumor tissue sample submitted for next-generation&#xD;
      sequencing (NGS) using FoundationOne® companion diagnostic (CDx) testing prior to entering&#xD;
      screening. If a participant has FoundationOne® CDx testing within five years of enrollment,&#xD;
      the previous tumor tissue may be re-analyzed for use in the study.&#xD;
&#xD;
      Depending on the cohort assignment per the tumor's biomarker profile, participants will be&#xD;
      assigned to the AFT-50A Protocol (atezolizumab+targeted agent) or the AFT-50B Protocol&#xD;
      (non-atezolizumab targeted agents). The current study cohorts are as follows:&#xD;
&#xD;
      AFT-50A Cohorts&#xD;
&#xD;
        -  Atezolizumab + Bevacizumab doublet&#xD;
&#xD;
        -  Atezolizumab + Ipatasertib doublet&#xD;
&#xD;
        -  Atezolizumab + Talazoparib doublet&#xD;
&#xD;
        -  Atezolizumab + Trastuzumab emtansine (TDM-1) doublet&#xD;
&#xD;
        -  Atezolizumab + Tiragolumab doublet&#xD;
&#xD;
      AFT-50B Cohorts&#xD;
&#xD;
      -Inavolisib + Letrozole doublet&#xD;
&#xD;
      It is anticipated that approximately 20 participants will be enrolled in each study cohort,&#xD;
      unless otherwise specified for a given cohort due to statistical considerations. Each study&#xD;
      cohort will open/close independently of other study cohorts. Once a study cohort reaches the&#xD;
      prespecified number of participants, it will be closed to further enrollment, unless an&#xD;
      expansion phase is planned.&#xD;
&#xD;
      The study is structured to allow for additional cohorts to be added as the study progresses.&#xD;
      These additional study cohorts may be proposed by investigators, but requires approval by the&#xD;
      Steering Committee in order to be added to the protocol.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">October 20, 2021</start_date>
  <completion_date type="Anticipated">October 2026</completion_date>
  <primary_completion_date type="Anticipated">October 1, 2025</primary_completion_date>
  <phase>Phase 1/Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Investigator-assessed overall response rate (ORR) of each biomarker cohort</measure>
    <time_frame>48 Months</time_frame>
    <description>AFT-50A Protocol: Overall response rate for each biomarker cohort is defined as the proportion of participants achieving a complete (CR) or partial (PR) response on two consecutive occasions at least 4 weeks apart, as determined by the investigator from AFT50A Protocol: Tumor assessments per RECIST v1.1.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>The proportion of participants in each biomarker cohort who remain alive and progression-free for at least 6 months</measure>
    <time_frame>6 Months</time_frame>
    <description>AFT-50B Protocol: Progression free survival rate at 6 months is defined as the proportion of participants who have not experienced disease progression or death from any cause at 6 months, as determined by the investigator according to RECIST v1.1</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Relative proportion of participants in each biomarker cohort who remain progression-free for at least 6 months compared to that from historical control studies</measure>
    <time_frame>6 Months per cohort</time_frame>
    <description>AFT-50A Protocol: PFS rate at 6 months is defined as the proportion of participants who have not experienced disease progression or death from any cause at 6 months, as determined by the investigator according to RECIST v1.1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Investigator assessed disease-control rate of each biomarker cohort</measure>
    <time_frame>48 Months</time_frame>
    <description>AFT-50A Protocol: Disease-control rate is defined as the proportion of participants achieving either stable disease, complete response, or partial response.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of response for participants in each biomarker cohort who achieve a complete or partial response.</measure>
    <time_frame>48 Months</time_frame>
    <description>AFT-50A Protocol: Duration of response is defined as the time from the first occurrence of a documented objective response to disease progression or death from any cause (whichever occurs first), as determined by the investigator according to RECIST v1.1.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival (OS) rates of participants in each biomarker cohort after 24 months</measure>
    <time_frame>24 Months per cohort</time_frame>
    <description>AFT-50A Protocol: 24-month overall survival rate is defined as the proportion of participants who have not experienced death from any cause at 24 months.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Investigator assessed disease-control rate of each biomarker cohort</measure>
    <time_frame>48 Months</time_frame>
    <description>AFT-50B Protocol: Disease control rate is defined as the proportion of participants achieving either stable disease, complete response, or partial response at any time.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of response for participants in each biomarker cohort who achieve a confirmed response (complete or partial)</measure>
    <time_frame>48 Months</time_frame>
    <description>AFT-50B Protocol: Duration of response is defined as the time from the first occurrence of a documented objective response (complete or partial) to disease progression or death from any cause (whichever occurs first), as determined by the investigator according to RECIST v1.1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival rates of participants in each biomarker cohort</measure>
    <time_frame>24 Months</time_frame>
    <description>AFT-50B Protocol: 24-month overall survival rate is defined as the proportion of participants who have not experienced death from any cause at 24 months.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Safety of each biomarker cohort: adverse events</measure>
    <time_frame>48 Months</time_frame>
    <description>AFT-50A Protocol: The incidence and severity of adverse events, with severity determined according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0), as well as summaries of changes in clinically relevant laboratory test results, changes in vital signs, and study treatment exposures for each biomarker cohort</description>
  </other_outcome>
  <other_outcome>
    <measure>The safety of each biomarker cohort: Adverse Events</measure>
    <time_frame>48 Months</time_frame>
    <description>AFT-50B Protocol: The incidence and severity of adverse events, with severity determined according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0). Summaries of changes in clinically relevant laboratory test results, changes in vital signs, and study treatment exposures for each biomarker cohort</description>
  </other_outcome>
  <other_outcome>
    <measure>Assess exploratory biomarkers in tumor tissue and peripheral blood, and their association with other molecular characteristics, disease status and/or participant response to study treatment</measure>
    <time_frame>48 Months</time_frame>
    <description>AFT-50A and AFT-50B Protocols: Association of exploratory biomarkers with clinical outcomes, including but not limited to molecular analysis of tumor tissue and peripheral blood, as well as cytokine/chemokine and cellular analysis of peripheral blood.</description>
  </other_outcome>
  <number_of_arms>6</number_of_arms>
  <enrollment type="Anticipated">124</enrollment>
  <condition>Endometrial Cancer</condition>
  <arm_group>
    <arm_group_label>Atezolizumab and Bevacizumab Cohort</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Following the submission of tumor tissue to Foundation Medicine for the FoundationOne® assay, participants with no specified gene signatures will be enrolled in this cohort. Twenty participants will be enrolled. Once twenty participants are enrolled, the cohort will be closed to further enrollment. Participants in this study cohort will commence treatment as specified on Day 1 of each cycle.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Atezolizumab and Ipatasertib Cohort</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Following the submission of tumor tissue to Foundation Medicine for the FoundationOne® assay, participants with PIK3CA/AKT1/PTEN-altered tumors will be enrolled in this cohort. Twenty participants will be enrolled. Once twenty participants are enrolled, the cohort will be closed to further enrollment. Participants in this study cohort will commence treatment as specified on Day 1 of each cycle.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Atezolizumab and Talazoparib Cohort</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Following the submission of tumor tissue to Foundation Medicine for the FoundationOne® assay, participants with tumors that have a ≥16%genomic loss of heterozygosity (LOH) will be assigned to this cohort. Twenty participants will be enrolled. Once twenty participants are enrolled, the cohort will be closed to further enrollment. Participants in this study cohort will commence treatment as specified on Day 1 of each cycle.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Atezolizumab and Trastuzumab emtansine (TDM-1) Cohort</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Following the submission of tumor tissue to Foundation Medicine for the FoundationOne® assay, participants with tumors that with an amplification of ERBB2/HER2 will be assigned to this cohort. Twenty participants will be enrolled. Once twenty participants are enrolled, the cohort will be closed to further enrollment. Participants in this study cohort will commence treatment as specified on Day 1 of each cycle.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Atezolizumab and Tiragolumab Cohort</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Following the submission of tumor tissue to Foundation Medicine for the FoundationOne® assay, participants with tumor type MSI-H and/or tTMB &gt;=10 mut/mb will be assigned to this cohort. Twenty participants will be enrolled initially. Once twenty participants are enrolled, the cohort may be expanded if a positive signal is shown. Participants in this study cohort will commence treatment as specified on Day 1 of each cycle.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Inavolisib and Letrozole Cohort</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Following the submission of tumor tissue to Foundation Medicine for the FoundationOne® assay, participants with tumors that with PIK3CA activating mutations in the absence of PTEN loss-of-function alterations or AKT1 activating mutations will be assigned to this cohort. Twenty-four participants will be enrolled. Once twenty-four participants are enrolled, the cohort will be closed to further enrollment. Participants in this study cohort will commence treatment as specified on Day 1 of each cycle.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Atezolizumab - 28 Day Cycle</intervention_name>
    <description>Atezolizumab will be given to participants intravenously at a dosage of 1680 mg on day 1 of each 28-day cycle.</description>
    <arm_group_label>Atezolizumab and Bevacizumab Cohort</arm_group_label>
    <arm_group_label>Atezolizumab and Ipatasertib Cohort</arm_group_label>
    <arm_group_label>Atezolizumab and Talazoparib Cohort</arm_group_label>
    <arm_group_label>Atezolizumab and Tiragolumab Cohort</arm_group_label>
    <other_name>Tecentriq</other_name>
    <other_name>L01XC32</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Bevacizumab</intervention_name>
    <description>Bevacizumab will be given to participants intravenously at a dosage of 10mg per participant kilogram every 2 weeks of the 28-day cycle.</description>
    <arm_group_label>Atezolizumab and Bevacizumab Cohort</arm_group_label>
    <other_name>Avastin</other_name>
    <other_name>L01XC07</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ipatasertib</intervention_name>
    <description>Ipatasertib will be given as an orally at a dosage of 400 mg once daily for 21 days of each 28-day cycle.</description>
    <arm_group_label>Atezolizumab and Ipatasertib Cohort</arm_group_label>
    <other_name>RG7440</other_name>
    <other_name>GDC-0068</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Talazoparib</intervention_name>
    <description>Talazoparib will be given in an orally at a dosage of 1 mg once daily for each day of the 28-day cycle.</description>
    <arm_group_label>Atezolizumab and Talazoparib Cohort</arm_group_label>
    <other_name>Talzenna</other_name>
    <other_name>L01XX60</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Trastuzumab emtansine</intervention_name>
    <description>Trastuzumab emtansine be given to participants intravenously at a dosage of 3.6 mg per participant kilogram, on day 1 of each 21-day cycle.</description>
    <arm_group_label>Atezolizumab and Trastuzumab emtansine (TDM-1) Cohort</arm_group_label>
    <other_name>T-DM1</other_name>
    <other_name>Kadcyla</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tiragolumab</intervention_name>
    <description>Tiragolumab will be given to participants intravenously at a dosage of 840 mg on day 1 of each 28-day cycle.</description>
    <arm_group_label>Atezolizumab and Tiragolumab Cohort</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Atezolizumab - 21 Day Cycle</intervention_name>
    <description>Atezolizumab will be given to participants intravenously at a dosage of 1200 mg on day 1 of each 21-day cycle.</description>
    <arm_group_label>Atezolizumab and Trastuzumab emtansine (TDM-1) Cohort</arm_group_label>
    <other_name>Tecentriq</other_name>
    <other_name>L01XC32</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Inavolisib</intervention_name>
    <description>Inavolisib will be given in an orally at a dosage of 9 mg once daily for each day of the 28-day cycle.</description>
    <arm_group_label>Inavolisib and Letrozole Cohort</arm_group_label>
    <other_name>GDC-0077</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Letrozole</intervention_name>
    <description>Letrozole will be given orally at a dosage of 2.5 mg once daily for each day of the 28-day cycle.</description>
    <arm_group_label>Inavolisib and Letrozole Cohort</arm_group_label>
    <other_name>Femara</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Key Inclusion Criteria:&#xD;
&#xD;
          -  Recurrent or persistent endometrial carcinoma which has progressed or recurred after&#xD;
             at least 1, but no more than 2, prior lines of therapy. Prior hormonal therapies&#xD;
             (e.g., tamoxifen, aromatase inhibitors) will not count toward the prior regimen limit.&#xD;
             Chemotherapy given in conjunction with radiotherapy as a radiosensitizer will be&#xD;
             counted as a systemic therapeutic regimen.&#xD;
&#xD;
          -  Measurable disease per RECIST 1.1&#xD;
&#xD;
          -  Availability of a representative tumor specimen that is suitable for determination of&#xD;
             biomarker status via central testing (F1CDx) OR If a patient has a prior F1CDx report&#xD;
             from 1 September 2019 or later, those NGS results can be used to determine biomarker&#xD;
             status as long as the tumor tissue used in the report was obtained within 5 years&#xD;
             prior to prescreening and appropriate signed consent is obtained from the patient.&#xD;
&#xD;
          -  Life expectancy &gt; 12 weeks&#xD;
&#xD;
          -  Recovery from effects of recent radiotherapy, surgery, or chemotherapy&#xD;
&#xD;
        Key Exclusion Criteria:&#xD;
&#xD;
          -  Endometrial tumors with the following histologies: squamous carcinomas, sarcomas&#xD;
&#xD;
          -  Other invasive malignancies within the last 5 years, except for non-melanoma skin&#xD;
             cancer with no evidence of disease within the past 5 years AND localized breast cancer&#xD;
             with previous adjuvant chemotherapy treatment for breast cancer completed &gt; 5 years&#xD;
             ago&#xD;
&#xD;
          -  Synchronous primary invasive ovarian or cervical cancer&#xD;
&#xD;
          -  Have an active or history of autoimmune disease or immune deficiency&#xD;
&#xD;
          -  Have a history of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced&#xD;
             pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis based on a&#xD;
             screening chest computed tomography (CT) scan&#xD;
&#xD;
          -  Active tuberculosis&#xD;
&#xD;
          -  Severe infections within 4 weeks&#xD;
&#xD;
          -  Have received therapeutic oral or IV antibiotic medication within 2 weeks, except&#xD;
             prophylactic antibiotic medication&#xD;
&#xD;
          -  Have significant cardiovascular disease&#xD;
&#xD;
          -  Are administered treatment with a live attenuated vaccine within 4 weeks, or&#xD;
             anticipation of need for such a vaccine during the course of the study&#xD;
&#xD;
          -  Have prior allogeneic bone marrow transplantation or solid organ transplant&#xD;
&#xD;
          -  Prior treatment with T-cell costimulating or immune checkpoint blockade therapies&#xD;
             including, but not limited to, CD137 agonists, anti-PD-1, anti-PD-L1, and anti-CTLA-4&#xD;
             therapeutic antibodies&#xD;
&#xD;
          -  History of treatment with systemic immunostimulatory agents (including but not limited&#xD;
             to interferons, interleukin-2) within 4 weeks or 5 half-lives of the drug, whichever&#xD;
             is longer, prior to initiation of study treatment&#xD;
&#xD;
          -  History of treatment with systemic immunosuppressive medications within 2 weeks except&#xD;
             acute, low-dose, systemic immunosuppressant medications, corticosteroids for chronic&#xD;
             obstructive pulmonary disease and asthma, or mineralocorticoids and low-dose&#xD;
             corticosteroids for participants with orthostatic hypotension or adrenocortical&#xD;
             insufficiency&#xD;
&#xD;
          -  Have a history or clinical evidence of any untreated CNS disease, seizures not&#xD;
             controlled with standard medical therapy, or history of cerebrovascular accident&#xD;
             (stroke), transient ischemic attack or subarachnoid hemorrhage within 6 months&#xD;
&#xD;
        Note: Additional study cohort specific inclusion and exclusion criteria may apply based on&#xD;
        cohort assignment.&#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_contact>
    <last_name>Quality Management and Compliance</last_name>
    <phone>617-732-8727</phone>
    <email>ClinicalTrials.Queries@alliancefoundationtrials.org</email>
  </overall_contact>
  <location>
    <facility>
      <name>City of Hope Comprehensive Cancer Center</name>
      <address>
        <city>Duarte</city>
        <state>California</state>
        <zip>91010</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Daphne Stewart</last_name>
    </contact>
    <investigator>
      <last_name>Daphne Stewart, MD, MS</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>UCSF Helen Diller Family Comprehensive Cancer Center</name>
      <address>
        <city>San Francisco</city>
        <state>California</state>
        <zip>94143</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Edwin Alvarez, MD</last_name>
    </contact>
    <investigator>
      <last_name>Edwin Alvarez, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Medstar Georgetown Cancer Institute</name>
      <address>
        <city>Washington</city>
        <state>District of Columbia</state>
        <zip>20007</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Ebony Hoskins, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Mount Sinai Comprehensive Cancer Center</name>
      <address>
        <city>Miami Beach</city>
        <state>Florida</state>
        <zip>33140</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Brian Slomovitz, MD</last_name>
    </contact>
    <investigator>
      <last_name>Brian Slomovitz, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>University of Chicago</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60637</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>John Moroney, MD</last_name>
    </contact>
    <investigator>
      <last_name>John Moroney, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Dana Farber Cancer Institute</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02125</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Joyce Liu, MD, MPH</last_name>
    </contact>
    <investigator>
      <last_name>Joyce Liu, MD, MPH</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>University of Minnesota</name>
      <address>
        <city>Minneapolis</city>
        <state>Minnesota</state>
        <zip>55455</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Britt Erickson, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Washington University School of Medicine Siteman Cancer Center</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63110</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Premal Thaker, MD, MS</last_name>
    </contact>
    <investigator>
      <last_name>Premal Thaker, MD, MS</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Nebraska Methodist Hospital</name>
      <address>
        <city>Omaha</city>
        <state>Nebraska</state>
        <zip>68114</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Brent Tierney, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Englewood Health</name>
      <address>
        <city>Englewood</city>
        <state>New Jersey</state>
        <zip>07631</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Nimesh Nagarsheth, MD</last_name>
    </contact>
    <investigator>
      <last_name>Nimesh Nagarsheth, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Atlantic Health Systems/Morristown Medical Center</name>
      <address>
        <city>Morristown</city>
        <state>New Jersey</state>
        <zip>07960</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Nana Tchabo, MD</last_name>
    </contact>
    <investigator>
      <last_name>Nana Tchabo, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Roswell Park</name>
      <address>
        <city>Buffalo</city>
        <state>New York</state>
        <zip>14263</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Peter Frederick, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Weill Cornell Medicine</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10065</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Evelyn Cantillo, MD, MPH</last_name>
    </contact>
    <investigator>
      <last_name>Evelyn Cantillo, MD, MPH</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Duke University Cancer Center</name>
      <address>
        <city>Durham</city>
        <state>North Carolina</state>
        <zip>27710</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Angeles Alvarez Secord, MD</last_name>
    </contact>
    <investigator>
      <last_name>Angeles Alvarez Secord, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Providence Portland Cancer Institute</name>
      <address>
        <city>Portland</city>
        <state>Oregon</state>
        <zip>97213</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Christopher Darus, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>University of Pittsburgh Medical Center</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15261</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Alexander B. Olawaiye, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Baptist Memorial Hospital</name>
      <address>
        <city>Memphis</city>
        <state>Tennessee</state>
        <zip>38120</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>David Engle, MD</last_name>
    </contact>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
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    <url>https://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm</url>
    <description>CTCAE Version 5.0</description>
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    <PMID>24625059</PMID>
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    <citation>Gockley AA, Kolin DL, Awtrey CS, Lindeman NI, Matulonis UA, Konstantinopoulos PA. Durable response in a woman with recurrent low-grade endometrioid endometrial cancer and a germline BRCA2 mutation treated with a PARP inhibitor. Gynecol Oncol. 2018 Aug;150(2):219-226. doi: 10.1016/j.ygyno.2018.05.028. Epub 2018 Jun 22.</citation>
    <PMID>29937315</PMID>
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    <citation>Jiao S, Xia W, Yamaguchi H, Wei Y, Chen MK, Hsu JM, Hsu JL, Yu WH, Du Y, Lee HH, Li CW, Chou CK, Lim SO, Chang SS, Litton J, Arun B, Hortobagyi GN, Hung MC. PARP Inhibitor Upregulates PD-L1 Expression and Enhances Cancer-Associated Immunosuppression. Clin Cancer Res. 2017 Jul 15;23(14):3711-3720. doi: 10.1158/1078-0432.CCR-16-3215. Epub 2017 Feb 6.</citation>
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    <citation>Strickland KC, Howitt BE, Shukla SA, Rodig S, Ritterhouse LL, Liu JF, Garber JE, Chowdhury D, Wu CJ, D'Andrea AD, Matulonis UA, Konstantinopoulos PA. Association and prognostic significance of BRCA1/2-mutation status with neoantigen load, number of tumor-infiltrating lymphocytes and expression of PD-1/PD-L1 in high grade serous ovarian cancer. Oncotarget. 2016 Mar 22;7(12):13587-98. doi: 10.18632/oncotarget.7277.</citation>
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  </reference>
  <verification_date>February 2023</verification_date>
  <study_first_submitted>July 22, 2020</study_first_submitted>
  <study_first_submitted_qc>July 23, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 24, 2020</study_first_posted>
  <last_update_submitted>February 8, 2023</last_update_submitted>
  <last_update_submitted_qc>February 8, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">February 10, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Endometrial Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Bevacizumab</mesh_term>
    <mesh_term>Trastuzumab</mesh_term>
    <mesh_term>Atezolizumab</mesh_term>
    <mesh_term>Ado-Trastuzumab Emtansine</mesh_term>
    <mesh_term>Letrozole</mesh_term>
    <mesh_term>Maytansine</mesh_term>
    <mesh_term>Talazoparib</mesh_term>
    <mesh_term>Ipatasertib</mesh_term>
    <mesh_term>Antibodies, Monoclonal</mesh_term>
    <mesh_term>Inavolisib</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</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/NCT04486352
org study id: AFT-50
nct id: NCT04486352
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This is a Phase IB/II multi-cohort study designed to evaluate the efficacy and safety of
      targeted agents with or without cancer immune checkpoint therapy with atezolizumab in
      participant with recurrent and/or persistent endometrial cancer. The main protocol provides a
      platform for genomic screening with homogeneous basic eligibility criteria in order to direct
      study participants into biomarker-matched study cohorts consisting of testing targeted
      agents.
This is a Phase IB/II multi-cohort study designed to evaluate the efficacy and safety of
      targeted agents with or without cancer immune checkpoint therapy with atezolizumab in
      participants with recurrent and/or persistent endometrial cancer.

      This biomarker-driven study provides a platform whereby participants with
      persistent/recurrent endometrial cancer will be placed into study cohorts evaluating targeted
      agents selected on the basis of the tumor's specific genomic profile. Prospective
      participants with persistent and/or recurrent endometrial cancer will be prescreened within
      60 days of treatment assignment to have a tumor tissue sample submitted for next-generation
      sequencing (NGS) using FoundationOne® companion diagnostic (CDx) testing prior to entering
      screening. If a participant has FoundationOne® CDx testing within five years of enrollment,
      the previous tumor tissue may be re-analyzed for use in the study.

      Depending on the cohort assignment per the tumor's biomarker profile, participants will be
      assigned to the AFT-50A Protocol (atezolizumab+targeted agent) or the AFT-50B Protocol
      (non-atezolizumab targeted agents). The current study cohorts are as follows:

      AFT-50A Cohorts

        -  Atezolizumab + Bevacizumab doublet

        -  Atezolizumab + Ipatasertib doublet

        -  Atezolizumab + Talazoparib doublet

        -  Atezolizumab + Trastuzumab emtansine (TDM-1) doublet

        -  Atezolizumab + Tiragolumab doublet

      AFT-50B Cohorts

      -Inavolisib + Letrozole doublet

      It is anticipated that approximately 20 participants will be enrolled in each study cohort,
      unless otherwise specified for a given cohort due to statistical considerations. Each study
      cohort will open/close independently of other study cohorts. Once a study cohort reaches the
      prespecified number of participants, it will be closed to further enrollment, unless an
      expansion phase is planned.

      The study is structured to allow for additional cohorts to be added as the study progresses.
      These additional study cohorts may be proposed by investigators, but requires approval by the
      Steering Committee in order to be added to the protocol.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Investigator-assessed overall response rate (ORR) of each biomarker cohort
time frame: 48 Months
description: AFT-50A Protocol: Overall response rate for each biomarker cohort is defined as the proportion of participants achieving a complete (CR) or partial (PR) response on two consecutive occasions at least 4 weeks apart, as determined by the investigator from AFT50A Protocol: Tumor assessments per RECIST v1.1.
measure: The proportion of participants in each biomarker cohort who remain alive and progression-free for at least 6 months
time frame: 6 Months
description: AFT-50B Protocol: Progression free survival rate at 6 months is defined as the proportion of participants who have not experienced disease progression or death from any cause at 6 months, as determined by the investigator according to RECIST v1.1
measure: Relative proportion of participants in each biomarker cohort who remain progression-free for at least 6 months compared to that from historical control studies
time frame: 6 Months per cohort
description: AFT-50A Protocol: PFS rate at 6 months is defined as the proportion of participants who have not experienced disease progression or death from any cause at 6 months, as determined by the investigator according to RECIST v1.1
measure: Investigator assessed disease-control rate of each biomarker cohort
time frame: 48 Months
description: AFT-50A Protocol: Disease-control rate is defined as the proportion of participants achieving either stable disease, complete response, or partial response.
measure: Duration of response for participants in each biomarker cohort who achieve a complete or partial response.
time frame: 48 Months
description: AFT-50A Protocol: Duration of response is defined as the time from the first occurrence of a documented objective response to disease progression or death from any cause (whichever occurs first), as determined by the investigator according to RECIST v1.1.
measure: Overall survival (OS) rates of participants in each biomarker cohort after 24 months
time frame: 24 Months per cohort
description: AFT-50A Protocol: 24-month overall survival rate is defined as the proportion of participants who have not experienced death from any cause at 24 months.
measure: Investigator assessed disease-control rate of each biomarker cohort
time frame: 48 Months
description: AFT-50B Protocol: Disease control rate is defined as the proportion of participants achieving either stable disease, complete response, or partial response at any time.
measure: Duration of response for participants in each biomarker cohort who achieve a confirmed response (complete or partial)
time frame: 48 Months
description: AFT-50B Protocol: Duration of response is defined as the time from the first occurrence of a documented objective response (complete or partial) to disease progression or death from any cause (whichever occurs first), as determined by the investigator according to RECIST v1.1
measure: Overall survival rates of participants in each biomarker cohort
time frame: 24 Months
description: AFT-50B Protocol: 24-month overall survival rate is defined as the proportion of participants who have not experienced death from any cause at 24 months.
measure: Safety of each biomarker cohort: adverse events
time frame: 48 Months
description: AFT-50A Protocol: The incidence and severity of adverse events, with severity determined according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0), as well as summaries of changes in clinically relevant laboratory test results, changes in vital signs, and study treatment exposures for each biomarker cohort
measure: The safety of each biomarker cohort: Adverse Events
time frame: 48 Months
description: AFT-50B Protocol: The incidence and severity of adverse events, with severity determined according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0). Summaries of changes in clinically relevant laboratory test results, changes in vital signs, and study treatment exposures for each biomarker cohort
measure: Assess exploratory biomarkers in tumor tissue and peripheral blood, and their association with other molecular characteristics, disease status and/or participant response to study treatment
time frame: 48 Months
description: AFT-50A and AFT-50B Protocols: Association of exploratory biomarkers with clinical outcomes, including but not limited to molecular analysis of tumor tissue and peripheral blood, as well as cytokine/chemokine and cellular analysis of peripheral blood.
arm group label: Atezolizumab and Bevacizumab Cohort
arm group type: Experimental
description: Following the submission of tumor tissue to Foundation Medicine for the FoundationOne® assay, participants with no specified gene signatures will be enrolled in this cohort. Twenty participants will be enrolled. Once twenty participants are enrolled, the cohort will be closed to further enrollment. Participants in this study cohort will commence treatment as specified on Day 1 of each cycle.
arm group label: Atezolizumab and Ipatasertib Cohort
arm group type: Experimental
description: Following the submission of tumor tissue to Foundation Medicine for the FoundationOne® assay, participants with PIK3CA/AKT1/PTEN-altered tumors will be enrolled in this cohort. Twenty participants will be enrolled. Once twenty participants are enrolled, the cohort will be closed to further enrollment. Participants in this study cohort will commence treatment as specified on Day 1 of each cycle.
arm group label: Atezolizumab and Talazoparib Cohort
arm group type: Experimental
description: Following the submission of tumor tissue to Foundation Medicine for the FoundationOne® assay, participants with tumors that have a ≥16%genomic loss of heterozygosity (LOH) will be assigned to this cohort. Twenty participants will be enrolled. Once twenty participants are enrolled, the cohort will be closed to further enrollment. Participants in this study cohort will commence treatment as specified on Day 1 of each cycle.
arm group label: Atezolizumab and Trastuzumab emtansine (TDM-1) Cohort
arm group type: Experimental
description: Following the submission of tumor tissue to Foundation Medicine for the FoundationOne® assay, participants with tumors that with an amplification of ERBB2/HER2 will be assigned to this cohort. Twenty participants will be enrolled. Once twenty participants are enrolled, the cohort will be closed to further enrollment. Participants in this study cohort will commence treatment as specified on Day 1 of each cycle.
arm group label: Atezolizumab and Tiragolumab Cohort
arm group type: Experimental
description: Following the submission of tumor tissue to Foundation Medicine for the FoundationOne® assay, participants with tumor type MSI-H and/or tTMB >=10 mut/mb will be assigned to this cohort. Twenty participants will be enrolled initially. Once twenty participants are enrolled, the cohort may be expanded if a positive signal is shown. Participants in this study cohort will commence treatment as specified on Day 1 of each cycle.
arm group label: Inavolisib and Letrozole Cohort
arm group type: Experimental
description: Following the submission of tumor tissue to Foundation Medicine for the FoundationOne® assay, participants with tumors that with PIK3CA activating mutations in the absence of PTEN loss-of-function alterations or AKT1 activating mutations will be assigned to this cohort. Twenty-four participants will be enrolled. Once twenty-four participants are enrolled, the cohort will be closed to further enrollment. Participants in this study cohort will commence treatment as specified on Day 1 of each cycle.
intervention type: Drug
intervention name: Atezolizumab - 28 Day Cycle
description: Atezolizumab will be given to participants intravenously at a dosage of 1680 mg on day 1 of each 28-day cycle.
arm group label: Atezolizumab and Bevacizumab Cohort
arm group label: Atezolizumab and Ipatasertib Cohort
arm group label: Atezolizumab and Talazoparib Cohort
arm group label: Atezolizumab and Tiragolumab Cohort
other name: Tecentriq
other name: L01XC32
intervention type: Drug
intervention name: Bevacizumab
description: Bevacizumab will be given to participants intravenously at a dosage of 10mg per participant kilogram every 2 weeks of the 28-day cycle.
arm group label: Atezolizumab and Bevacizumab Cohort
other name: Avastin
other name: L01XC07
intervention type: Drug
intervention name: Ipatasertib
description: Ipatasertib will be given as an orally at a dosage of 400 mg once daily for 21 days of each 28-day cycle.
arm group label: Atezolizumab and Ipatasertib Cohort
other name: RG7440
other name: GDC-0068
intervention type: Drug
intervention name: Talazoparib
description: Talazoparib will be given in an orally at a dosage of 1 mg once daily for each day of the 28-day cycle.
arm group label: Atezolizumab and Talazoparib Cohort
other name: Talzenna
other name: L01XX60
intervention type: Drug
intervention name: Trastuzumab emtansine
description: Trastuzumab emtansine be given to participants intravenously at a dosage of 3.6 mg per participant kilogram, on day 1 of each 21-day cycle.
arm group label: Atezolizumab and Trastuzumab emtansine (TDM-1) Cohort
other name: T-DM1
other name: Kadcyla
intervention type: Drug
intervention name: Tiragolumab
description: Tiragolumab will be given to participants intravenously at a dosage of 840 mg on day 1 of each 28-day cycle.
arm group label: Atezolizumab and Tiragolumab Cohort
intervention type: Drug
intervention name: Atezolizumab - 21 Day Cycle
description: Atezolizumab will be given to participants intravenously at a dosage of 1200 mg on day 1 of each 21-day cycle.
arm group label: Atezolizumab and Trastuzumab emtansine (TDM-1) Cohort
other name: Tecentriq
other name: L01XC32
intervention type: Drug
intervention name: Inavolisib
description: Inavolisib will be given in an orally at a dosage of 9 mg once daily for each day of the 28-day cycle.
arm group label: Inavolisib and Letrozole Cohort
other name: GDC-0077
intervention type: Drug
intervention name: Letrozole
description: Letrozole will be given orally at a dosage of 2.5 mg once daily for each day of the 28-day cycle.
arm group label: Inavolisib and Letrozole Cohort
other name: Femara
criteria: 
gender: Female
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Quality Management and Compliance
phone: 617-732-8727
email: ClinicalTrials.Queries@alliancefoundationtrials.org
facility: 
status: Recruiting
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facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
country: United States
url: https://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm
description: CTCAE Version 5.0
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responsible party type: Sponsor
mesh term: Endometrial Neoplasms
mesh term: Bevacizumab
mesh term: Trastuzumab
mesh term: Atezolizumab
mesh term: Ado-Trastuzumab Emtansine
mesh term: Letrozole
mesh term: Maytansine
mesh term: Talazoparib
mesh term: Ipatasertib
mesh term: Antibodies, Monoclonal
mesh term: Inavolisib
sharing ipd: No