What is the mechanism of action of this treatment?

Immune checkpoint inhibitors like Atezolizumab enhance the immune system's ability to recognize and attack endometrial cancer cells by blocking proteins that inhibit immune responses. This is particularly effective for tumors with high mutational burdens, such as those that are mismatch repair-deficient (dMMR) or microsatellite instability-high (MSI-H). Additionally, targeted therapies focus on specific genetic mutations, and endocrine therapies modulate hormone levels to slow cancer growth. These treatments are vital for providing personalized and potentially more effective options for patients with recurrent or persistent endometrial cancer, especially when traditional chemotherapy fails.

What side effects are associated with this type of intervention?

Common treatments for endometrial cancer, particularly immune checkpoint inhibitors like atezolizumab, can cause side effects such as fatigue, rash, diarrhea, and immune-related adverse events including colitis, hepatitis, endocrinopathies (e.g., hypothyroidism), and pneumonitis. These occur due to the enhanced immune response that can sometimes target normal tissues. When combined with chemotherapy, additional side effects may include nausea, vomiting, neutropenia, and neuropathy.

What prior FDA approvals exist?

The FDA has approved several treatments for Endometrial Cancer, including immune checkpoint inhibitors similar to Atezolizumab. Pembrolizumab, another immune checkpoint inhibitor targeting PD-1, has been approved for use in patients with advanced endometrial cancer that is microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) and has progressed following prior treatment. Additionally, the combination of pembrolizumab and lenvatinib, a tyrosine kinase inhibitor, has been approved for patients with advanced endometrial cancer that is not MSI-H or dMMR and has progressed after prior systemic therapy. These approvals highlight the growing role of immunotherapy in the treatment of endometrial cancer.

What other types of research exist?

Promising alternatives to Atezolizumab for endometrial cancer patients include Pembrolizumab, which has shown safety and antitumor activity in PD-L1-positive advanced endometrial cancer in the KEYNOTE-028 study. Additionally, targeted agents identified through genomic screening in multi-cohort studies may offer novel treatment options.

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PD-L1 Inhibitor

Targeted Therapy + Atezolizumab for Endometrial Cancer (EndoMAP Trial)

Phase 1 & 2

Recruiting

Research Sponsored by Alliance Foundation Trials, LLC.

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Be older than 18 years old

Must not have

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

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 48 months

Awards & highlights

No Placebo-Only Group

Summary

This trial tests drugs that target cancer cells, sometimes combined with an immune-boosting drug called atezolizumab. It focuses on patients with endometrial cancer that has returned or is persistent. The drugs are chosen based on the genetic profile of the patient's tumor to improve effectiveness.

Who is the study for?

This trial is for individuals with recurrent or persistent endometrial cancer who have undergone no more than two prior treatments (excluding certain hormonal therapies and radiosensitizers). Participants must have a life expectancy over 12 weeks, measurable disease per RECIST 1.1, and a suitable tumor specimen for biomarker testing. Those with autoimmune diseases, severe infections recently, significant cardiovascular disease, other recent malignancies except certain skin cancers and localized breast cancer treated over 5 years ago are excluded.

What is being tested?

The study evaluates the effectiveness of targeted agents like Abemaciclib, Giredestrant, Talazoparib among others in combination with or without Atezolizumab—an immune checkpoint therapy—in treating endometrial cancer. It's designed to match participants to treatment based on specific biomarkers identified through genomic screening.

What are the potential side effects?

Potential side effects include reactions related to the immune system such as inflammation in various organs due to atezolizumab; organ-specific toxicity from targeted agents; increased risk of infection; fatigue; digestive issues; blood disorders; and possible infusion-related reactions.

Eligibility Criteria

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have not received a live vaccine in the last 4 weeks and do not plan to during the study.

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I have had a bone marrow or organ transplant in the past.

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I have a history of lung scarring or inflammation not caused by infections.

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I have been diagnosed with ovarian or cervical cancer at the same time.

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I have active tuberculosis.

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I have a serious heart condition.

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My endometrial cancer is either squamous carcinoma or sarcoma.

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I have previously received treatments that boost the immune system to fight cancer.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 48 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~48 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and 48 months for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

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

The proportion of participants in each biomarker cohort who remain alive and progression-free for at least 6 months

Secondary study objectives

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

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

Investigator assessed disease-control rate of each biomarker cohort

+3 more

Other study objectives

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

Safety of each biomarker cohort: adverse events

The safety of each biomarker cohort: Adverse Events

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

7Treatment groups

Experimental Treatment

Group I: Inavolisib and Letrozole CohortExperimental Treatment2 Interventions

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.

Group II: Giredestrant and AbemaciclibExperimental Treatment2 Interventions

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.

Group III: Atezolizumab and Trastuzumab emtansine (TDM-1) CohortExperimental Treatment2 Interventions

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.

Group IV: Atezolizumab and Tiragolumab CohortExperimental Treatment2 Interventions

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.

Group V: Atezolizumab and Talazoparib CohortExperimental Treatment2 Interventions

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.

Group VI: Atezolizumab and Ipatasertib CohortExperimental Treatment2 Interventions

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.

Group VII: Atezolizumab and Bevacizumab CohortExperimental Treatment2 Interventions

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.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Talazoparib

2021

Completed Phase 2

~2810

Trastuzumab emtansine

2010

Completed Phase 4

~2290

Giredestrant

2019

Completed Phase 2

~300

Tiragolumab

2019

Completed Phase 3

~1390

Inavolisib

2021

Completed Phase 2

~260

Letrozole

2002

Completed Phase 4

~3590

Abemaciclib

2019

Completed Phase 2

~1890

Bevacizumab

2013

Completed Phase 4

~5540

Ipatasertib

2017

Completed Phase 3

~3630

0 / 8Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Immune checkpoint inhibitors like Atezolizumab enhance the immune system's ability to recognize and attack endometrial cancer cells by blocking proteins that inhibit immune responses. This is particularly effective for tumors with high mutational burdens, such as those that are mismatch repair-deficient (dMMR) or microsatellite instability-high (MSI-H). Additionally, targeted therapies focus on specific genetic mutations, and endocrine therapies modulate hormone levels to slow cancer growth. These treatments are vital for providing personalized and potentially more effective options for patients with recurrent or persistent endometrial cancer, especially when traditional chemotherapy fails.

Immuno-Oncology for Gynecologic Malignancies.Optimizing immunotherapy for gynecologic cancers.Immunotherapy in endometrial cancer: new scenarios on the horizon.