Recruiting
Phase 1
Phase 2

Targeted Agents

Sponsor:

Alliance Foundation Trials, LLC.

Code:

NCT04486352

Conditions

Endometrial Cancer

Eligibility Criteria

Sex: Female

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Atezolizumab - 28 Day Cycle

Bevacizumab

Ipatasertib

Talazoparib

Trastuzumab emtansine

Study Details

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.

Conditions

Endometrial Cancer

Study ID

NCT04486352

Start date

Oct 20, 2021

Status verified date

Jul, 2025

Completion date

Oct, 2027

Anticipated

Primary completion date

Oct 1, 2026

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: Female

Age: 18+

Healthy Volunteers: Not accepted

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 Design

Enrollment

148 participants

Anticipated

Allocation

Non randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Atezolizumab and Bevacizumab Cohort - Closed to Accrual

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.

experimental: Atezolizumab and Ipatasertib Cohort - Closed to Accrual

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.

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.

experimental: Atezolizumab and Trastuzumab emtansine (TDM-1) Cohort - Closed to Accrual

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.

experimental: Atezolizumab and Tiragolumab Cohort - Closed to Accrual

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.

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.

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

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.

Bevacizumab

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

Ipatasertib

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

Talazoparib

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

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.

Tiragolumab

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

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.

Inavolisib

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

Letrozole

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

Giredestrant

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

Abemaciclib

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

Primary outcome measure

  • Investigator-assessed overall response rate (ORR) of each biomarker cohort [ Time Frame: 48 Months ]
  • The proportion of participants in each biomarker cohort who remain alive and progression-free for at least 6 months [ Time Frame: 6 Months ]

Central Contacts and Locations

Central contacts

Quality Management and Compliance

617-732-8727ClinicalTrials.Queries@alliancefoundationtrials.org

Locations

University of Oklahoma Health Stephenson Cancer Center

Recruiting

Oklahoma City, Oklahoma, United States, 73104

Principal Investigator:

Debra Richardson, MD

More Information

Sponsor

Alliance Foundation Trials, LLC.

Last update posted

Apr 1, 2026

Last verified

Jul, 2025

Trial information was received from ClinicalTrials.gov and was last updated on 2026-10-09. This information was provided to ClinicalTrials.gov by Alliance Foundation Trials, LLC. on 2026-04-01. Recruitment status is synced daily from ClinicalTrials.gov and may not reflect the sponsor's current status. Confirm during your call.