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EndoMAP: A Study of Targeted Agents With Atezolizumab for Patients With Recurrent or Persistent Endometrial Cancer

Sponsor
Alliance Foundation Trials, LLC. (Other)
Overall Status
Recruiting
CT.gov ID
NCT04486352
Collaborator
Genentech, Inc. (Industry), Foundation Medicine (Industry), Pfizer (Industry)
100
Enrollment
14
Locations
5
Arms
59.4
Anticipated Duration (Months)
7.1
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a Phase IB/II multi-cohort study designed to evaluate the efficacy and safety of targeted agents plus cancer immune checkpoint therapy with atezolizumab for patients 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 subjects into biomarker-matched study cohorts consisting of testing targeted agents with atezolizumab.

Condition or Disease Intervention/Treatment Phase
Phase 1/Phase 2

Detailed Description

This is a Phase IB/II multi-cohort study designed to evaluate the efficacy and safety of targeted agents plus cancer immune checkpoint therapy with atezolizumab in patients with recurrent and/or persistent endometrial cancer.

This biomarker-driven study provides a platform whereby patients with persistent/recurrent endometrial cancer will be placed into study cohorts evaluating atezolizumab plus a targeted agent selected on the basis of the tumor's specific genomic profile. Prospective patients 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.

Based on the FoundationOne® results, patients will be assigned to a study cohort with a targeted therapy + atezolizumab. The current study cohorts are as follows:

  • Atezolizumab + Bevacizumab doublet

  • Atezolizumab + Ipatasertib doublet

  • Atezolizumab + Talazoparib doublet

  • Atezolizumab + Trastuzumab emtansine (TDM-1) doublet

  • Atezolizumab + Tiragolumab doublet

It is anticipated that 20 patients will be enrolled in each study cohort. Each study cohort will open/close independently of other study cohorts. Once a study cohort reaches 20 patients, it will be closed to further enrollment.

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.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
100 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase IB/II Multi-Cohort Study of Targeted Agents With Atezolizumab for Patients With Recurrent or Persistent Endometrial Cancer
Actual Study Start Date :
Oct 20, 2021
Anticipated Primary Completion Date :
Oct 1, 2025
Anticipated Study Completion Date :
Oct 1, 2026

Arms and Interventions

Arm Intervention/Treatment
Experimental: Atezolizumab and Bevacizumab Cohort

Following the submission of tumor tissue to Foundation Medicine for the FoundationOne® assay, patients with no specified gene signatures will be enrolled in this cohort. Twenty patients will be enrolled. Once twenty patientsare enrolled, the cohort will be closed to further enrollment. Patients in this study cohort will commence treatment as specified on Day 1 of each cycle.

Drug: Atezolizumab - 28 Day Cycle
Atezolizumab will be given to patients intravenously at a dosage of 1680 mg on day 1 of each 28-day cycle.
Other Names:
  • Tecentriq
  • L01XC32

    • Drug: Bevacizumab
    Bevacizumab will be given to patients intravenously at a dosage of 10mg per patient kilogram every 2 weeks of the 28-day cycle.
    Other Names:
  • Avastin
  • L01XC07

    		•
    Experimental: Atezolizumab and Ipatasertib Cohort

    Following the submission of tumor tissue to Foundation Medicine for the FoundationOne® assay, patients with PIK3CA/AKT1/PTEN-altered tumors will be enrolled in this cohort. Twenty patients will be enrolled. Once twenty patients are enrolled, the cohort will be closed to further enrollment. Patients in this study cohort will commence treatment as specified on Day 1 of each cycle.

    Drug: Atezolizumab - 28 Day Cycle
    Atezolizumab will be given to patients intravenously at a dosage of 1680 mg on day 1 of each 28-day cycle.
    Other Names:
  • Tecentriq
  • L01XC32

    • Drug: Ipatasertib
    Ipatasertib will be given as an oral tablet at a dosage of 400 mg once daily for 21 days of each 28-day cycle.
    Other Names:
  • RG7440
  • GDC-0068

    		•
    Experimental: Atezolizumab and Talazoparib Cohort

    Following the submission of tumor tissue to Foundation Medicine for the FoundationOne® assay, patients with tumors that have a ≥16%genomic loss of heterozygosity (LOH) will be assigned to this cohort. Twenty patients will be enrolled. Once twenty patients are enrolled, the cohort will be closed to further enrollment. Patients in this study cohort will commence treatment as specified on Day 1 of each cycle.

    Drug: Atezolizumab - 28 Day Cycle
    Atezolizumab will be given to patients intravenously at a dosage of 1680 mg on day 1 of each 28-day cycle.
    Other Names:
  • Tecentriq
  • L01XC32

    • Drug: Talazoparib
    Talazoparib will be given in an oral tablet at a dosage of 1 mg once daily for each day of the 28-day cycle.
    Other Names:
  • Talzenna
  • L01XX60

    		•
    Experimental: Atezolizumab and Trastuzumab emtansine (TDM-1) Cohort

    Following the submission of tumor tissue to Foundation Medicine for the FoundationOne® assay, patients with tumors that with an amplification of ERBB2/HER2 will be assigned to this cohort. Twenty patients will be enrolled. Once twenty patients are enrolled, the cohort will be closed to further enrollment. Patients in this study cohort will commence treatment as specified on Day 1 of each cycle.

    Drug: Trastuzumab emtansine
    Trastuzumab emtansine be given to patients intravenously at a dosage of 3.6 mg per patient kilogra, on day 1 of each 21-day cycle.
    Other Names:
  • T-DM1
  • Kadcyla

    • Drug: Atezolizumab - 21 Day Cycle
    Atezolizumab will be given to patients intravenously at a dosage of 1200 mg on day 1 of each 21-day cycle.
    Other Names:
  • Tecentriq
  • L01XC32

    		•
    Experimental: Atezolizumab and Tiragolumab Cohort

    Following the submission of tumor tissue to Foundation Medicine for the FoundationOne® assay, patients with tumor type MSI-H and/or tTMB >=10 mut/mb will be assigned to this cohort. Twenty patients will be enrolled initially. Once twenty patients are enrolled, the cohort may be expanded if a positive signal is shown. Patients in this study cohort will commence treatment as specified on Day 1 of each cycle.

    Drug: Atezolizumab - 28 Day Cycle
    Atezolizumab will be given to patients intravenously at a dosage of 1680 mg on day 1 of each 28-day cycle.
    Other Names:
  • Tecentriq
  • L01XC32

    • Drug: Tiragolumab
    Tiragolumab will be given to patients intravenously at a dosage of 840 mg on day 1 of each 28-day cycle.

    Outcome Measures

    Primary Outcome Measures

    1. Investigator-assessed overall response rate (ORR) of each biomarker cohort [48 Months]

      Overall response rate for each biomarker cohort is defined as the proportion of patients achieving a complete (CR) or partial (PR) response on two consecutive occasions at least 4 weeks apart, as determined by the investigator from tumor assessments per RECIST v1.1.

    Secondary Outcome Measures

    1. Relative proportion of patients in each biomarker cohort who remain progression-free for at least 6 months compared to that from historical control studies [6 Months per cohort]

      PFS rate at 6 months is defined as the proportion of patients who have not experienced disease progression or death from any cause at 6 months, as determined by the investigator according to RECIST v1.1

    2. Investigator assessed disease-control rate of each biomarker cohort [48 Months]

      Disease-control rate is defined as the proportion of patients achieving either stable disease, complete response, or partial response.

    3. Duration of response for patients in each biomarker cohort who achieve a complete or partial response. [48 Months]

      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.

    4. Overall survival (OS) rates of patients in each biomarker cohort after 24 months [24 Months per cohort]

      24-month overall survival rate is defined as the proportion of patients who have not experienced death from any cause at 24 months.

    Other Outcome Measures

    1. Safety of each biomarker cohort: adverse events [48 Months]

      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

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    Female
    Accepts Healthy Volunteers:
    No
    Key Inclusion Criteria:

    • Recurrent or persistent endometrial carcinoma which has progressed or recurred after at least 1, but no more than 2, prior lines of therapy. Prior hormonal therapies (e.g., tamoxifen, aromatase inhibitors) will not count toward the prior regimen limit. Chemotherapy given in conjunction with radiotherapy as a radiosensitizer will be counted as a systemic therapeutic regimen.

    • Measurable disease per RECIST 1.1

    • Formalin-fixed, paraffin-embedded tumor tissue, a specimen as proximal to the current recurrence as possible, must be submitted to the Central Lab for molecular testing (FoundationOne CDxTM)

    • Life expectancy > 12 weeks

    • Recovery from effects of recent radiotherapy, surgery, or chemotherapy

    Key Exclusion Criteria:

    • Endometrial tumors with the following histologies: squamous carcinomas, sarcomas

    • Other invasive malignancies within the last 5 years, except for non-melanoma skin cancer with no evidence of disease within the past 5 years AND localized breast cancer with previous adjuvant chemotherapy treatment for breast cancer completed > 5 years ago

    • Synchronous primary invasive ovarian or cervical cancer

    • Have an active or history of autoimmune disease or immune deficiency

    • Have a history of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis based on a screening chest computed tomography (CT) scan

    • Active tuberculosis

    • Severe infections within 4 weeks

    • Have received therapeutic oral or IV antibiotic medication within 2 weeks, except prophylactic antibiotic medication

    • Have significant cardiovascular disease

    • Are administered treatment with a live attenuated vaccine within 4 weeks, or anticipation of need for such a vaccine during the course of the study

    • Have prior allogeneic bone marrow transplantation or solid organ transplant

    • Prior treatment with T-cell costimulating or immune checkpoint blockade therapies including, but not limited to, CD137 agonists, anti-PD-1, anti-PD-L1, and anti-CTLA-4 therapeutic antibodies

    • History of treatment with systemic immunostimulatory agents (including but not limited to interferons, interleukin-2) within 4 weeks or 5 half-lives of the drug, whichever is longer, prior to initiation of study treatment

    • History of treatment with systemic immunosuppressive medications within 2 weeks except acute, low-dose, systemic immunosuppressant medications, corticosteroids for chronic obstructive pulmonary disease and asthma, or mineralocorticoids and low-dose corticosteroids for patients with orthostatic hypotension or adrenocortical insufficiency

    • Have a history or clinical evidence of any untreated CNS disease, seizures not controlled with standard medical therapy, or history of cerebrovascular accident (stroke), transient ischemic attack or subarachnoid hemorrhage within 6 months

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 City of Hope Comprehensive Cancer Center Duarte California United States 91010
    2 University of San Francisco Medical Center San Francisco California United States 94143
    3 Mount Sinai Comprehensive Cancer Center Miami Beach Florida United States 33140
    4 University of Chicago Chicago Illinois United States 60637
    5 Dana Farber Cancer Institute Boston Massachusetts United States 02125
    6 University of Minnesota Minneapolis Minnesota United States 55455
    7 Washington University School of Medicine Siteman Cancer Center Saint Louis Missouri United States 63110
    8 Nebraska Methodist Hospital Omaha Nebraska United States 68114
    9 Englewood Health Englewood New Jersey United States 07631
    10 Atlantic Health Systems/Morristown Medical Center Morristown New Jersey United States 07960
    11 Roswell Park Buffalo New York United States 14263
    12 Weill Cornell Medicine New York New York United States 10065
    13 Duke University Cancer Center Durham North Carolina United States 27710
    14 University of Pittsburgh Medical Center Pittsburgh Pennsylvania United States 15261

    Sponsors and Collaborators

    • Alliance Foundation Trials, LLC.
    • Genentech, Inc.
    • Foundation Medicine
    • Pfizer

    Investigators

    None specified.

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    Responsible Party:
    Alliance Foundation Trials, LLC.
    ClinicalTrials.gov Identifier:
    NCT04486352
    Other Study ID Numbers:
    • AFT-50
    First Posted:
    Jul 24, 2020
    Last Update Posted:
    Jun 9, 2022
    Last Verified:
    Jun 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:
    Endometrial Neoplasms
    Bevacizumab
    Trastuzumab
    Ado-Trastuzumab Emtansine
    Atezolizumab
    Maytansine
    Talazoparib
    Antibodies, Monoclonal

    Study Results

    No Results Posted as of Jun 9, 2022