What side effects are associated with this type of intervention?

Common treatments for endometrial cancer, particularly those involving PD-L1 inhibitors like Avelumab, PARP inhibitors like Talazoparib, and Tyrosine Kinase Inhibitors like Axitinib, have a range of side effects. PD-L1 inhibitors can cause immune-related side effects such as fatigue, rash, diarrhea, and severe conditions like pneumonitis and colitis. PARP inhibitors often lead to nausea, fatigue, anemia, and blood cell count reductions. Tyrosine kinase inhibitors are associated with hypertension, diarrhea, fatigue, hand-foot syndrome, and liver enzyme abnormalities. Combining these treatments may increase both the likelihood and severity of these side effects.

What prior FDA approvals exist?

The FDA has approved several drugs for the treatment of endometrial cancer, particularly focusing on immunotherapy and targeted therapy. Pembrolizumab, a PD-1 inhibitor similar to Avelumab, has been approved for use in patients with advanced endometrial cancer that is microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR). Additionally, the combination of pembrolizumab with lenvatinib, a tyrosine kinase inhibitor, has been approved for advanced endometrial cancer following prior systemic therapy. While there are no specific FDA approvals for PARP inhibitors like Talazoparib in endometrial cancer, these drugs are being actively studied in clinical trials for their potential benefits.

What other types of research exist?

Promising alternatives for endometrial cancer treatment in 2024 include the combination of Lenvatinib (a tyrosine kinase inhibitor) and Pembrolizumab (an immune checkpoint inhibitor), which has shown significant efficacy in clinical trials. Additionally, ongoing research into other PARP inhibitors like Olaparib and Niraparib, as well as novel combinations involving Bevacizumab (an angiogenesis inhibitor), may offer new therapeutic options.

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Monoclonal Antibodies

Avelumab + Talazoparib/Axitinib for Endometrial Cancer

Q: What is the mechanism of action of this treatment?

Avelumab, a PD-L1 inhibitor, works by blocking the PD-L1 protein on cancer cells, which helps the immune system recognize and attack these cells. Talazoparib, a PARP inhibitor, prevents cancer cells from repairing their DNA, leading to cell death, particularly in cells with existing DNA repair deficiencies. Axitinib, a tyrosine kinase inhibitor, blocks enzymes involved in the growth of blood vessels that supply tumors, thereby inhibiting tumor growth. These treatments are significant for endometrial cancer patients as they offer targeted approaches that can enhance the effectiveness of the immune system, disrupt cancer cell survival mechanisms, and reduce tumor vascularization, potentially leading to better outcomes.

Phase 2

Waitlist Available

Led By Panagiotis Konstantinopoulos, MD, PhD

Research Sponsored by Dana-Farber Cancer Institute

Eligibility Criteria Checklist

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

Must have

Age of 18 or greater years. Because insufficient dosing or adverse event data are currently available on the use of Avelumab, talazoparib, and/or axitinib in participants < 18 years of age, children are excluded from the study. Endometrial cancer is very rare in the pediatric population.

Additional inclusion criteria for the avelumab/axitinib cohort: Participants must have adequately controlled blood pressure and LVEF ≥ lower limit of normal (LLN) as assessed by either multigated acquisition (MUGA) scan or echocardiogram (ECHO)

Must not have

Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) related illness

Clinically significant (i.e., active) cardiovascular disease

Timeline

Screening 3 weeks

Treatment Varies

Follow Up participants are followed for survival status from registration through up to 3 years after removal from study intervention

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing Avelumab alone and with Talazoparib or Axitinib to treat endometrial cancer that has returned or spread. It aims to see if these drugs can help patients whose cancer hasn't responded to other treatments by boosting the immune system, stopping DNA repair in cancer cells, or blocking blood vessel growth. These drugs are being explored for their potential in treating endometrial cancer.

Who is the study for?

This trial is for women with recurrent or persistent endometrial cancer who haven't used PD-1/PD-L1 pathway drugs, PARP inhibitors (for certain cohorts), or axitinib. They must be adults with at least one prior chemotherapy regimen, not pregnant/breastfeeding, and have normal organ/marrow function. Participants need measurable disease by RECIST 1.1 standards and no severe illnesses that could interfere.

What is being tested?

The study tests Avelumab alone and in combination with Talazoparib or Axitinib for treating endometrial cancer that has returned or hasn't responded to treatment. It aims to find out how well these treatments work on different genetic types of the cancer: MSS, MSI-H, and POLE-mutated.

What are the potential side effects?

Possible side effects include immune-related reactions due to Avelumab (like inflammation in organs), blood pressure changes from Axitinib use, and bone marrow suppression which might lead to anemia or infections because of Talazoparib.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I am 18 years old or older.

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My blood pressure is under control and my heart's pumping ability is normal.

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My endometrial cancer falls into either the MSI/POLE or MSS category.

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I have had at least one chemotherapy treatment for endometrial cancer.

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I am 18 years old or older.

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My endometrial cancer has a specific POLE mutation.

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I have a tumor or lymph node that meets the size requirements for measurement.

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I am fully active or can carry out light work.

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Side effects from my previous treatments are mild.

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I have never taken axitinib.

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My organs and bone marrow are functioning normally.

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I have never taken PARP inhibitor therapy.

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My endometrial cancer is MSI-H due to a lack of certain proteins.

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I have never taken PARP inhibitors before.

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I can provide a tissue sample from my cancer surgery or biopsy.

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I have never taken axitinib.

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I have not taken drugs targeting the PD-1/PD-L1 pathway.

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I have not taken drugs targeting the PD-1/PD-L1 pathway.

Exclusion Criteria

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

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I have an illness related to HIV or AIDS.

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I have an active heart condition.

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I have brain metastases.

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I have been treated with drugs targeting the immune system for cancer.

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I am currently on medication for an infection.

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I do not have any uncontrolled illnesses.

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I have severe stomach or intestinal problems.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ participants are followed for survival status from registration through up to 3 years after removal from study intervention

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~participants are followed for survival status from registration through up to 3 years after removal from study intervention

This trial's timeline: 3 weeks for screening, Varies for treatment, and participants are followed for survival status from registration through up to 3 years after removal from study intervention for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Objective Response Rate

Progression-Free Survival at 6 Months

Secondary study objectives

Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v4.0

Overall Survival

Progression-Free Survival

Side effects data

From 2020 Phase 2 trial • 19 Patients • NCT03006848

17%

Musculoskeletal and connective tissue disorders

11%

Injury, poisoning and procedural complications

General disorders and administration site conditions

Metabolism and nutrition disorders

Endocrine disorders

Nervous system disorders

Investigations

Cardiac disorders

Gastrointestinal disorders

Infections and infestations

Immune system disorders

Blood and lymphatic system disorders

Neoplasms benign, malignant and unspecified

Respiratory, thoracic and mediastinal disorders

Renal and urinary disorders

Skin and subcutaneous tissue disorders

100%

80%

60%

40%

20%

Study treatment Arm

Avelumab

Awards & Highlights

No Placebo-Only Group

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

Trial Design

4Treatment groups

Experimental Treatment

Group I: Pole Mutated Endometrial CancerExperimental Treatment1 Intervention

Participants with Pole mutated endometrial cancer Avelumab will be administered intravenously twice per cycle

Group II: MSS Endometrial CancerExperimental Treatment1 Intervention

Participants with MSS mutated endometrial cancer Avelumab will be administered intravenously twice per cycle

Group III: MSS Avelumab/Talazoparib Combination ArmExperimental Treatment2 Interventions

Participants with MSS mutated endometrial cancer Avelumab will be administered intravenously twice per cycle Talazoparib will be administered one time per day by mouth

Group IV: MSS Avelumab/Axitinib Combination ArmExperimental Treatment2 Interventions

Participants with MSS mutated endometrial cancer Avelumab will be administered intravenously twice per cycle Axitinib will be administered twice per day by mouth

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Avelumab

2017

Completed Phase 2

~2440

Talazoparib

2021

Completed Phase 2

~2810

Axitinib

2020

Completed Phase 2

~3050

0 / 25Eligibility 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

Avelumab, a PD-L1 inhibitor, works by blocking the PD-L1 protein on cancer cells, which helps the immune system recognize and attack these cells. Talazoparib, a PARP inhibitor, prevents cancer cells from repairing their DNA, leading to cell death, particularly in cells with existing DNA repair deficiencies. Axitinib, a tyrosine kinase inhibitor, blocks enzymes involved in the growth of blood vessels that supply tumors, thereby inhibiting tumor growth. These treatments are significant for endometrial cancer patients as they offer targeted approaches that can enhance the effectiveness of the immune system, disrupt cancer cell survival mechanisms, and reduce tumor vascularization, potentially leading to better outcomes.

Evaluation of Treatment With Talazoparib and Avelumab in Patients With Recurrent Mismatch Repair Proficient Endometrial Cancer.PARP Inhibition Elicits STING-Dependent Antitumor Immunity in Brca1-Deficient Ovarian Cancer.