Avelumab + Talazoparib/Axitinib for Endometrial Cancer

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

106 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

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.

What data supports the effectiveness of the drug combination Avelumab + Talazoparib/Axitinib for Endometrial Cancer?

Research shows that drugs targeting the PD-1/PD-L1 pathway, like pembrolizumab, have been effective in treating certain types of advanced endometrial cancer, especially when combined with other treatments. This suggests that similar drugs, such as Avelumab, might also be effective in combination therapies for endometrial cancer. ^{1 2 3 4 5}

How is the drug Avelumab + Talazoparib/Axitinib unique for treating endometrial cancer?

Avelumab is a unique drug for endometrial cancer because it is an immune checkpoint inhibitor that targets the PD-L1 pathway, potentially enhancing the body's immune response against cancer cells. This combination with Talazoparib or Axitinib is novel as it explores the synergy between immune modulation and other targeted therapies, which is different from the more established treatments like pembrolizumab and lenvatinib. ^{3 4 6 7 8}

Research Team

Panagiotis Konstantinopoulos, MD, PhD

Principal Investigator

Dana-Farber Cancer Institute

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

A phase II trial of brivanib in recurrent or persistent endometrial cancer: an NRG Oncology/Gynecologic Oncology Group Study. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

Obesity is associated with improved progression-free survival in Microsatellite-Instability-High endometrial cancer treated with pembrolizumab. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Real-world experience of pembrolizumab and lenvatinib in recurrent endometrial cancer: A multicenter study in Korea. [2022]

4. Switzerland 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. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

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

6. England pubmed.ncbi.nlm.nih.gov

Avelumab (anti-PD-L1) in platinum-resistant/refractory ovarian cancer: JAVELIN Ovarian 200 Phase III study design. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Uterine serous carcinoma. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab as a single agent for patients with MSI-H advanced endometrial carcinoma. [2022]