Avelumab + Talazoparib/Axitinib for Endometrial Cancer

Not currently recruiting at 3 trial locations

Overseen By DFCI Clinical Trials Hotline

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: Dana-Farber Cancer Institute

Must not be taking: PD-1/PD-L1 inhibitors, PARP inhibitors

Disqualifiers: Brain metastases, HIV/AIDS, Hepatitis B/C, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 6 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the drug Avelumab (also known as MSB0010718C or Bavencio), both alone and combined with either Talazoparib (Talzenna) or Axitinib (Inlyta), to determine their effectiveness in treating recurrent or metastatic endometrial cancer. The study includes different groups to explore these drugs in various ways, aiming to find effective treatments for this type of cancer. Candidates for this trial should have endometrial cancer that has returned or spread and have undergone at least one round of chemotherapy. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot use certain herbal products or medications that strongly affect liver enzymes. It's best to discuss your current medications with the study team to see if any adjustments are needed.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that Avelumab has been used safely for other cancers, such as Merkel cell carcinoma. It is usually well-tolerated, though serious immune reactions can occur, but these are rare.

For those considering Avelumab with Talazoparib, studies indicate they are mostly safe together. About 25.7% of patients experienced serious side effects, such as low platelet counts and small bowel blockages, though these were uncommon.

The combination of Avelumab and Axitinib also has an acceptable safety profile. The FDA has approved it for treating advanced kidney cancer, suggesting it is considered fairly safe for certain conditions.

In summary, while some risks exist, previous studies suggest these treatments are generally safe for many patients. Always discuss potential side effects with a healthcare provider. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for endometrial cancer because they offer innovative approaches compared to standard care, which usually involves surgery, radiation, or traditional chemotherapy. Avelumab, an immune checkpoint inhibitor, helps the body's immune system recognize and attack cancer cells more effectively. The combination of Avelumab with Talazoparib or Axitinib introduces additional mechanisms: Talazoparib is a PARP inhibitor that prevents cancer cells from repairing their DNA, while Axitinib targets and inhibits proteins that promote blood vessel growth in tumors. Together, these treatments could potentially enhance the effectiveness of existing therapies and provide new hope for patients with endometrial cancer.

What evidence suggests that this trial's treatments could be effective for endometrial cancer?

In this trial, participants with MSS mutated endometrial cancer will receive different treatment combinations. Some participants will receive Avelumab alone, while others will receive a combination of Avelumab and Talazoparib, or Avelumab and Axitinib. A previous study found that Avelumab alone was not very effective for patients with MSS endometrial cancer, especially those with TP53 mutations. However, combining Avelumab with Talazoparib provided some benefits, though the overall results were modest. The combination of Avelumab and Axitinib showed promising results and was generally safe for patients with recurring endometrial cancer. While Avelumab and Axitinib are approved for treating other cancers like kidney cancer, their use for endometrial cancer remains under investigation. These treatments have potential, but further research is needed to confirm their effectiveness for endometrial cancer. ^{1 6 7 8 9}

Who Is on the Research Team?

Panagiotis Konstantinopoulos, MD, PhD

Principal Investigator

Dana-Farber Cancer Institute

Are You a Good Fit for This Trial?

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.

Inclusion Criteria

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

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

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

Exclusion Criteria

I haven't had chemotherapy or radiotherapy in the last 4 weeks and have recovered from any side effects.

You have an autoimmune disease that may get worse if you take a medication that boosts your immune system.

I have not taken immunosuppressive drugs in the last 7 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Avelumab alone or in combination with Talazoparib or Axitinib for recurrent or metastatic endometrial cancer

6 months

Intravenous administration twice per cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 39 months

Long-term follow-up

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

Up to 3 years

What Are the Treatments Tested in This Trial?

Interventions

• Avelumab
• Axitinib
• Talazoparib

Trial Overview 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.

How Is the Trial Designed?

Group I: Pole Mutated Endometrial Cancer Experimental Treatment 1 Intervention

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

Group II: MSS Endometrial Cancer Experimental Treatment 1 Intervention

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

Group III: MSS Avelumab/Talazoparib Combination Arm Experimental Treatment 2 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 Arm Experimental Treatment 2 Interventions

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

Avelumab is already approved in European Union, United States, Japan for the following indications:

Approved in European Union as Bavencio for:

• Merkel cell carcinoma
• Renal cell carcinoma
• Urothelial carcinoma

Approved in United States as Bavencio for:

• Merkel cell carcinoma
• Renal cell carcinoma
• Urothelial carcinoma

Approved in Japan as Bavencio for:

• Merkel cell carcinoma
• Renal cell carcinoma
• Urothelial carcinoma

Who Is Running the Clinical Trial?

Dana-Farber Cancer Institute

Lead Sponsor

Trials

1,128

Recruited

382,000+

Pfizer

Industry Sponsor

Trials

4,712

Recruited

50,980,000+

Known For

Vaccine Innovations

Top Products

Viagra, Zoloft, Lipitor, Prevnar 13

Albert Bourla

Pfizer

Chief Executive Officer since 2019

PhD in Biotechnology of Reproduction, Aristotle University of Thessaloniki

Patrizia Cavazzoni

Pfizer

Chief Medical Officer

MD from McGill University

Published Research Related to This Trial

In a study of 48 patients with recurrent endometrial cancer treated with pembrolizumab and lenvatinib, the best objective response rate was 23.8%, indicating a lower effectiveness compared to clinical trial results.

The treatment was associated with notable side effects, with 56.2% of patients requiring a dose reduction of lenvatinib and 16.7% discontinuing treatment due to adverse events, highlighting the importance of monitoring for safety in real-world settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world experience of pembrolizumab and lenvatinib in recurrent endometrial cancer: A multicenter study in Korea. Kim, J., Noh, JJ., Lee, TK., et al.[2022]

The JAVELIN Ovarian 200 trial is the first Phase III study to investigate the effectiveness of avelumab, a PD-L1 checkpoint inhibitor, in treating women with platinum-resistant ovarian cancer, involving multiple treatment arms to assess its efficacy.

The trial will measure overall survival and progression-free survival as primary outcomes, providing valuable insights into the potential benefits of avelumab alone or in combination with doxorubicin compared to doxorubicin alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Avelumab (anti-PD-L1) in platinum-resistant/refractory ovarian cancer: JAVELIN Ovarian 200 Phase III study design. Pujade-Lauraine, E., Fujiwara, K., Dychter, SS., et al.[2022]

Pembrolizumab, an immune checkpoint inhibitor, has been approved for treating relapsed MSI-H endometrial cancer after chemotherapy, showing promise in restoring anti-tumor immunity by blocking PD-1 interactions.

Despite encouraging response rates in MSI-H patients, over 50% do not respond to pembrolizumab, highlighting the need for better understanding of MSI status and identifying specific patient populations that may benefit from treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab as a single agent for patients with MSI-H advanced endometrial carcinoma. Turinetto, M., Lombardo, V., Pisano, C., et al.[2022]

In a study of 44 women with advanced or recurrent MMRd/MSI-H endometrial adenocarcinomas treated with pembrolizumab, obesity (BMI≥30) was linked to a higher disease control rate (85.2%) compared to those with a BMI<30 (59.8%).

Patients with obesity also experienced significantly longer progression-free survival (PFS) while overall survival (OS) rates remained similar regardless of BMI, suggesting that body weight may influence treatment outcomes with pembrolizumab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Obesity is associated with improved progression-free survival in Microsatellite-Instability-High endometrial cancer treated with pembrolizumab. Bernard, L., How, JA., Patel, S., et al.[2023]

The phase III RUBY and NRG-GY018 trials demonstrated that women with newly diagnosed or first-recurrent advanced endometrial cancer benefit from combining a PD-1 inhibitor (dostarlimab or pembrolizumab) with standard chemotherapy.

This combination treatment significantly prolonged progression-free survival, and there was a positive trend in overall survival, indicating its potential effectiveness in managing this type of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ICI-Chemo New Standard for Endometrial Cancer. [2023]

Pembrolizumab and dostarlimab, immune checkpoint inhibitors, have been approved for treating advanced recurrent endometrial cancer in patients with specific molecular subgroups, particularly those with mismatch repair deficiency (MMRd) or microsatellite instability-high (MSI-H) status, based on data from 15 studies involving 1609 patients.

The combination of pembrolizumab or dostarlimab with lenvatinib has shown efficacy in patients with mismatch repair proficient/microsatellite stable (MMRp/MSS) endometrial cancer, highlighting the importance of biomarker assessment to optimize treatment strategies for different molecular phenotypes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immune Checkpoint Inhibitors Targeting the PD-1/PD-L1 Pathway in Advanced, Recurrent Endometrial Cancer: A Scoping Review with SWOT Analysis. Johnson, RL., Ganesan, S., Thangavelu, A., et al.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9798913/

Phase II Study of Avelumab in Patients With Mismatch ... Avelumab was administered on an outpatient basis at 10 mg/kg intravenously every 2 weeks until progression or unacceptable toxicity. Antitumor activity was ...

2. esmo.org esmo.org/oncology-news/avelumab-ineffective-in-patients-with-mss-endometrial-cancer-carrying-tp53-mutation

Avelumab Ineffective in Patients with MSS Endometrial ... The MITO END-3 study results suggest that TP53 mutation is associated with a poor effect of avelumab, while mutations of PTEN and ARID1A are ...

3. jamanetwork.com jamanetwork.com/journals/jamaoncology/fullarticle/2794808

Evaluation of Treatment With Talazoparib and Avelumab in ... Overall, 9 patients (25.7%) derived clinical benefit from treatment with avelumab and talazoparib after meeting 1 or more of the 2 coprimary end ...

4. aetna.com aetna.com/cpb/medical/data/900_999/0916.html

Avelumab (Bavencio) - Medical Clinical Policy Bulletins Out of the total 226 patients evaluable for efficacy, 44% had non-bladder urothelial carcinoma, including 23% of patients with upper tract disease; 83% of ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0090825825008376

Phase 2, two-stage study of avelumab and axitinib in ... The confirmed objective response was 25.7 %, DOR was 13.8 months and median PFS was 7 months. •. 78.1 % of patients had TP53 mutated tumors and 21.9 % NSMP ...

6. go.drugbank.com go.drugbank.com/drugs/DB11945

Avelumab: Uses, Interactions, Mechanism of Action Avelumab is indicated for the treatment of adults with metastatic Merkel cell carcinoma (MCC). 8,9 In the US, it is also used in patients 12 years and older.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT02912572

NCT02912572 | Avelumab in Patients With MSS, MSI-H ... 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 ...

8. es.aetna.com es.aetna.com/cpb/medical/data/900_999/0916.html

Avelumab (Bavencio) - Medical Clinical Policy Bulletins The authors concluded that both pembrolizumab and nivolumab showed promising efficacy with acceptable safety data in published trials in GI cancers, especially ...

9. bavencio.com bavencio.com/en_US/hcp.html

BAVENCIO® (avelumab) For Healthcare Professionals IMPORTANT SAFETY INFORMATION. BAVENCIO can cause severe and fatal immune-mediated adverse reactions in any organ system or tissue and at any time after starting ...