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RecruitingInterventionalPhase 1/Phase 2

A Phase IB/II Multi-Cohort Study of Targeted Agents and/or Immunotherapy With Atezolizumab for Patients With Recurrent or Persistent Endometrial Cancer

NCT ID: NCT04486352Sponsor: Alliance Foundation Trials, LLC.Last updated: 2026-04-01

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. Non-FMI NGS testing may be submitted if approved. 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 - Closed to Accrual * Atezolizumab + Ipatasertib doublet - Closed to Accrual * Atezolizumab + Talazoparib doublet * Atezolizumab + Trastuzumab emtansine (TDM-1) doublet - Closed to Accrual * Atezolizumab + Tiragolumab doublet - Closed to Accrual 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.

Arms & interventions

  • DrugAtezolizumab - 28 Day Cycle

    Atezolizumab will be given to participants intravenously at a dosage of 1680 mg on day 1 of each 28-day cycle.

  • DrugBevacizumab

    Bevacizumab will be given to participants intravenously at a dosage of 10mg per participant kilogram every 2 weeks of the 28-day cycle.

  • DrugIpatasertib

    Ipatasertib will be given as an orally at a dosage of 400 mg once daily for 21 days of each 28-day cycle.

  • DrugTalazoparib

    Talazoparib will be given in an orally at a dosage of 1 mg once daily for each day of the 28-day cycle.

  • DrugTrastuzumab 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.

  • DrugTiragolumab

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

  • DrugAtezolizumab - 21 Day Cycle

    Atezolizumab will be given to participants intravenously at a dosage of 1200 mg on day 1 of each 21-day cycle.

  • DrugInavolisib

    Inavolisib will be given in an orally at a dosage of 9 mg once daily for each day of the 28-day cycle.

  • DrugLetrozole

    Letrozole will be given orally at a dosage of 2.5 mg once daily for each day of the 28-day cycle.

  • DrugGiredestrant

    Giredestrant will be given orally at a dosage of 30 mg once daily for each day of the 28-day cycle.

  • DrugAbemaciclib

    Giredestrant will be given orally at a dosage of 150 mg twice daily for each day of the 28-day cycle.

Outcome measures

Primary

  • Investigator-assessed overall response rate (ORR) of each biomarker cohort

    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.

    Time frame: 48 Months

  • The proportion of participants in each biomarker cohort who remain alive and progression-free for at least 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

    Time frame: 6 Months

Secondary

  • 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

  • Investigator assessed disease-control rate of each biomarker cohort

    Time frame: 48 Months

  • Duration of response for participants in each biomarker cohort who achieve a complete or partial response.

    Time frame: 48 Months

  • Overall survival (OS) rates of participants in each biomarker cohort after 24 months

    Time frame: 24 Months per cohort

  • Investigator assessed disease-control rate of each biomarker cohort

    Time frame: 48 Months

  • Duration of response for participants in each biomarker cohort who achieve a confirmed response (complete or partial)

    Time frame: 48 Months

  • Overall survival rates of participants in each biomarker cohort

    Time frame: 24 Months

Eligibility criteria

Sex: FemaleAge: 18 Years and olderHealthy 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 * 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 * 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 AFT-50A Specific Exclusion Criteria: ● 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 Note: Additional study cohort specific inclusion and exclusion criteria may apply based on cohort assignment.

Study locations (21)

City of Hope Comprehensive Cancer Center

Duarte, California, 91010

Active Not Recruiting

UCSF Helen Diller Family Comprehensive Cancer Center

San Francisco, California, 94143

Active Not Recruiting

Medstar Georgetown Cancer Institute

Washington D.C., District of Columbia, 20007

Active Not Recruiting

Mount Sinai Comprehensive Cancer Center

Miami Beach, Florida, 33140

Active Not Recruiting

University of Chicago

Chicago, Illinois, 60637

Active Not Recruiting

University of Kansas Cancer Center

Westwood, Kansas, 66205

Active Not Recruiting

Maine Medical Center

Scarborough, Maine, 04074

Active Not Recruiting

Dana Farber Cancer Institute

Boston, Massachusetts, 02125

Active Not Recruiting

University of Minnesota

Minneapolis, Minnesota, 55455

Active Not Recruiting

Washington University School of Medicine Siteman Cancer Center

St Louis, Missouri, 63110

Withdrawn

Nebraska Methodist Hospital

Omaha, Nebraska, 68114

Active Not Recruiting

Englewood Health

Englewood, New Jersey, 07631

Active Not Recruiting

Atlantic Health Systems/Morristown Medical Center

Morristown, New Jersey, 07960

Active Not Recruiting

Roswell Park

Buffalo, New York, 14263

Active Not Recruiting

Weill Cornell Medicine

New York, New York, 10065

Active Not Recruiting

Duke University Cancer Center

Durham, North Carolina, 27710

Active Not Recruiting

University of Oklahoma Health Stephenson Cancer Center

Oklahoma City, Oklahoma, 73104

Recruiting
Debra Richardson, MD · Contact
Debra Richardson, MD · Principal Investigator

Providence Portland Cancer Institute

Portland, Oregon, 97213

Active Not Recruiting

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15261

Active Not Recruiting

Lifespan - Rhode Island Hospital

Providence, Rhode Island, 02903

Active Not Recruiting

Baptist Memorial Hospital

Memphis, Tennessee, 38120

Withdrawn

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