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A Study of Targeted Agents for Patients With Recurrent or Persistent Endometrial Cancer (EndoMAP)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04486352
Recruitment Status : Recruiting
First Posted : July 24, 2020
Last Update Posted : December 26, 2023
Sponsor:
Collaborators:
Genentech, Inc.
Foundation Medicine
Pfizer
Eli Lilly and Company
Information provided by (Responsible Party):
Alliance Foundation Trials, LLC.

Tracking Information
First Submitted Date  ICMJE July 22, 2020
First Posted Date  ICMJE July 24, 2020
Last Update Posted Date December 26, 2023
Actual Study Start Date  ICMJE October 20, 2021
Estimated Primary Completion Date October 1, 2025   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 8, 2023)
  • Investigator-assessed overall response rate (ORR) of each biomarker cohort [ Time Frame: 48 Months ]
    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.
  • The proportion of participants in each biomarker cohort who remain alive and progression-free for at least 6 months [ Time Frame: 6 Months ]
    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
Original Primary Outcome Measures  ICMJE
 (submitted: July 23, 2020)		 Investigator-assessed overall response rate (ORR) of each biomarker cohort [ Time Frame: 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.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 8, 2023)
  • 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 ]
    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
  • Investigator assessed disease-control rate of each biomarker cohort [ Time Frame: 48 Months ]
    AFT-50A Protocol: Disease-control rate is defined as the proportion of participants achieving either stable disease, complete response, or partial response.
  • Duration of response for participants in each biomarker cohort who achieve a complete or partial response. [ Time Frame: 48 Months ]
    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.
  • Overall survival (OS) rates of participants in each biomarker cohort after 24 months [ Time Frame: 24 Months per cohort ]
    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.
  • Investigator assessed disease-control rate of each biomarker cohort [ Time Frame: 48 Months ]
    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.
  • Duration of response for participants in each biomarker cohort who achieve a confirmed response (complete or partial) [ Time Frame: 48 Months ]
    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
  • Overall survival rates of participants in each biomarker cohort [ Time Frame: 24 Months ]
    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.
Original Secondary Outcome Measures  ICMJE
 (submitted: July 23, 2020)
  • Relative proportion of patients 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 ]
    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
  • Investigator assessed disease-control rate of each biomarker cohort [ Time Frame: 48 Months ]
    Disease-control rate is defined as the proportion of patients achieving either stable disease, complete response, or partial response.
  • Duration of response for patients in each biomarker cohort who achieve a complete or partial response. [ Time Frame: 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.
  • Overall survival (OS) rates of patients in each biomarker cohort after 24 months [ Time Frame: 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.
Current Other Pre-specified Outcome Measures
 (submitted: February 8, 2023)
  • Safety of each biomarker cohort: adverse events [ Time Frame: 48 Months ]
    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
  • The safety of each biomarker cohort: Adverse Events [ Time Frame: 48 Months ]
    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
  • 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 ]
    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.
Original Other Pre-specified Outcome Measures
 (submitted: July 23, 2020)		 Safety of each biomarker cohort: adverse events [ Time Frame: 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
 
Descriptive Information
Brief Title  ICMJE A Study of Targeted Agents for Patients With Recurrent or Persistent Endometrial Cancer
Official Title  ICMJE A Phase IB/II Multi-Cohort Study of Targeted Agents and/or Immunotherapy With Atezolizumab for Patients With Recurrent or Persistent Endometrial Cancer
Brief Summary 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.
Detailed Description

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
  • Giredestrant + Abemaciclib doublet

It is anticipated that approximately 20 participants will be enrolled in each study cohort in AFT-50A and 24 participants in each study cohort in AFT-50B, 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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Endometrial Cancer
Intervention  ICMJE
  • Drug: Atezolizumab - 28 Day Cycle
    Atezolizumab will be given to participants 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 participants intravenously at a dosage of 10mg per participant kilogram every 2 weeks of the 28-day cycle.
    Other Names:
    • Avastin
    • L01XC07
  • Drug: Ipatasertib
    Ipatasertib will be given as an orally at a dosage of 400 mg once daily for 21 days of each 28-day cycle.
    Other Names:
    • RG7440
    • GDC-0068
  • Drug: Talazoparib
    Talazoparib will be given in an orally at a dosage of 1 mg once daily for each day of the 28-day cycle.
    Other Names:
    • Talzenna
    • L01XX60
  • Drug: Trastuzumab emtansine
    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.
    Other Names:
    • T-DM1
    • Kadcyla
  • Drug: Tiragolumab
    Tiragolumab will be given to participants intravenously at a dosage of 840 mg on day 1 of each 28-day cycle.
  • Drug: Atezolizumab - 21 Day Cycle
    Atezolizumab will be given to participants intravenously at a dosage of 1200 mg on day 1 of each 21-day cycle.
    Other Names:
    • Tecentriq
    • L01XC32
  • Drug: Inavolisib
    Inavolisib will be given in an orally at a dosage of 9 mg once daily for each day of the 28-day cycle.
    Other Name: GDC-0077
  • Drug: Letrozole
    Letrozole will be given orally at a dosage of 2.5 mg once daily for each day of the 28-day cycle.
    Other Name: Femara
  • Drug: Giredestrant
    Giredestrant will be given orally at a dosage of 30 mg once daily for each day of the 28-day cycle.
    Other Name: GDC-9545
  • Drug: Abemaciclib
    Giredestrant will be given orally at a dosage of 150 mg twice daily for each day of the 28-day cycle.
    Other Name: Verzenio
Study Arms  ICMJE
  • Experimental: Atezolizumab and Bevacizumab Cohort
    Following the submission of tumor tissue for the FoundationOne® companion diagnostic (F1CDx) test, 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.
    Interventions:
    • Drug: Atezolizumab - 28 Day Cycle
    • Drug: Bevacizumab
  • Experimental: Atezolizumab and Ipatasertib Cohort
    Following the submission of tumor tissue for the FoundationOne® companion diagnostic (F1CDx) test, 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.
    Interventions:
    • Drug: Atezolizumab - 28 Day Cycle
    • Drug: Ipatasertib
  • Experimental: Atezolizumab and Talazoparib Cohort
    Following the submission of tumor tissue for the FoundationOne® companion diagnostic (F1CDx) test, 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.
    Interventions:
    • Drug: Atezolizumab - 28 Day Cycle
    • Drug: Talazoparib
  • Experimental: Atezolizumab and Trastuzumab emtansine (TDM-1) Cohort
    Following the submission of tumor tissue for the FoundationOne® companion diagnostic (F1CDx) test, 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.
    Interventions:
    • Drug: Trastuzumab emtansine
    • Drug: Atezolizumab - 21 Day Cycle
  • Experimental: Atezolizumab and Tiragolumab Cohort
    Following the submission of tumor tissue for the FoundationOne® companion diagnostic (F1CDx) test, 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.
    Interventions:
    • Drug: Atezolizumab - 28 Day Cycle
    • Drug: Tiragolumab
  • Experimental: Inavolisib and Letrozole Cohort
    Following the submission of tumor tissue for the FoundationOne® companion diagnostic (F1CDx) test, 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.
    Interventions:
    • Drug: Inavolisib
    • Drug: Letrozole
  • Experimental: Giredestrant and Abemaciclib
    Following the submission of tumor tissue for the FoundationOne® companion diagnostic (F1CDx) test, participants with tumors that are RB1 intact with a local grade 1-2 estrogne receptor positive (ER+) are 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.
    Interventions:
    • Drug: Giredestrant
    • Drug: Abemaciclib
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: October 17, 2023)		 148
Original Estimated Enrollment  ICMJE
 (submitted: July 23, 2020)		 60
Estimated Study Completion Date  ICMJE October 2026
Estimated Primary Completion Date October 1, 2025   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
  • Availability of a representative tumor specimen that is suitable for determination of biomarker status via central testing (F1CDx) OR If a patient has a prior F1CDx report from 1 September 2019 or later, those NGS results can be used to determine biomarker status as long as the tumor tissue used in the report was obtained within 5 years prior to prescreening and appropriate signed consent is obtained from the patient.
  • 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 participants 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

Note: Additional study cohort specific inclusion and exclusion criteria may apply based on cohort assignment.
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Quality Management and Compliance 617-732-8727 ClinicalTrials.Queries@alliancefoundationtrials.org
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04486352
Other Study ID Numbers  ICMJE AFT-50
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Current Responsible Party Alliance Foundation Trials, LLC.
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Alliance Foundation Trials, LLC.
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE
  • Genentech, Inc.
  • Foundation Medicine
  • Pfizer
  • Eli Lilly and Company
Investigators  ICMJE Not Provided
PRS Account Alliance Foundation Trials, LLC.
Verification Date December 2023

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP