Pembrolizumab + Bevacizumab for Ovarian Cancer

Recruiting at 1 trial location

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: Roswell Park Cancer Institute

Must not be taking: Immunosuppressants, Corticosteroids, PARP inhibitors, others

Disqualifiers: Active CNS metastases, Autoimmune disease, 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

Compensation: Varies

Number of Visits: 33

Duration: Up to 2 years

80 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot use certain treatments like immunosuppressive medications, systemic corticosteroids, or investigational drugs shortly before starting the trial. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug combination Pembrolizumab and Bevacizumab for ovarian cancer?

Research shows that Bevacizumab, when combined with other chemotherapy drugs, can significantly prolong the time patients with ovarian cancer live without the disease getting worse. Pembrolizumab has shown antitumor activity in patients with advanced ovarian cancer, suggesting potential benefits when used in combination with Bevacizumab. ^{1 2 3 4 5}

Is the combination of Pembrolizumab and Bevacizumab safe for humans?

Pembrolizumab and Bevacizumab have been studied separately for safety in humans. Pembrolizumab has been evaluated for safety in advanced ovarian cancer, while Bevacizumab has been used in various cancers, including ovarian cancer. Bevacizumab can cause mild side effects like high blood pressure and bleeding, but serious side effects like gastrointestinal issues are rare. Overall, both drugs have been generally safe in clinical trials, but they can have side effects that should be monitored. ^{1 6 7 8 9}

How is the drug combination of Pembrolizumab and Bevacizumab unique for treating ovarian cancer?

The combination of Pembrolizumab and Bevacizumab for ovarian cancer is unique because it combines an immune checkpoint inhibitor (Pembrolizumab) that helps the immune system attack cancer cells, with an anti-angiogenic drug (Bevacizumab) that prevents the growth of blood vessels that supply tumors, offering a novel approach compared to traditional chemotherapy. ^{1 2 3 10 11}

What is the purpose of this trial?

This phase II trial tests whether pembrolizumab combined with bevacizumab with or without agonist anti-CD40 CDX-1140 works to shrink tumors in patients with ovarian cancer that has come back (recurrent). Anti-CD40 CDX-1140 works by stimulating certain immune cells within the tumor and, when combined with other immunotherapy treatments, may increase antitumor antibody production. Immunotherapy with monoclonal antibodies, such as pembrolizumab and bevacizumab, may help the body's immune system, and may interfere with the ability of tumor cells to grow and spread. Giving pembrolizumab and bevacizumab with anti-CD40 CDX-1140 may decrease symptoms, prolonged survival, and improve quality of life in patients with ovarian cancer.

Research Team

Emese Zsiros

Principal Investigator

Roswell Park Cancer Institute

Eligibility Criteria

This trial is for adults over 18 with recurrent ovarian cancer, including serous, endometrioid, or clear cell types. Participants can have had up to three prior treatments and must be expected to live more than six months. They should be relatively active (ECOG status of 0 or 1) and able to undergo a biopsy. Pregnant women are excluded, as well as those with certain medical conditions or severe allergies.

Inclusion Criteria

I am not pregnant.

I am willing to have a biopsy of my tumor.

My cancer is a recurring ovarian, fallopian tube, or peritoneal type.

Exclusion Criteria

Any condition deemed unsuitable by the investigator

I am able to understand and consent to medical procedures.

Known immunodeficiency or active human immunodeficiency virus (HIV)

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive pembrolizumab and bevacizumab with or without CDX-1140 intravenously every 3 weeks until disease progression or unacceptable toxicity

Up to 2 years

Every 3 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

30 days post-treatment, then every 6 months

Treatment Details

Interventions

• Bevacizumab
• CDX-1140
• Pembrolizumab

Trial Overview The study tests pembrolizumab combined with bevacizumab and possibly anti-CD40 CDX-1140 in patients whose ovarian cancer has returned. It aims to see if this combination can shrink tumors by stimulating the immune system and producing antitumor antibodies.

Participant Groups

Group I: Arm II (pembrolizumab, bevacizumab, CDX-1140) Experimental Treatment 5 Interventions

Patients receive pembrolizumab IV over 30 minutes, bevacizumab IV over 30-90 minutes, and CDX-1140 IV over 90 minutes on day 1. Cycles repeat every 3 weeks until disease progression or development of unacceptable toxicity.

Group II: Arm I (pembrolizumab, bevacizumab) Active Control 4 Interventions

Patients receive pembrolizumab IV over 30 minutes and bevacizumab IV over 30-90 minutes on day 1. Cycles repeat every 3 weeks until disease progression or development of unacceptable toxicity.

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

Approved in European Union as Avastin for:

• Colorectal cancer
• Breast cancer
• Non-small cell lung cancer
• Renal cell carcinoma
• Ovarian cancer

Approved in United States as Avastin for:

• Colorectal cancer
• Non-small cell lung cancer
• Glioblastoma
• Renal cell carcinoma
• Cervical cancer
• Ovarian cancer

Approved in Japan as Avastin for:

• Colorectal cancer
• Non-small cell lung cancer
• Breast cancer
• Renal cell carcinoma
• Ovarian cancer

Approved in Canada as Avastin for:

• Colorectal cancer
• Non-small cell lung cancer
• Breast cancer
• Renal cell carcinoma
• Ovarian cancer

Who Is Running the Clinical Trial?

Roswell Park Cancer Institute

Lead Sponsor

Trials

427

Recruited

40,500+

United States Department of Defense

Collaborator

Trials

940

Recruited

339,000+

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Celldex Therapeutics

Industry Sponsor

Trials

66

Recruited

5,900+

Anthony S. Marucci

Celldex Therapeutics

Chief Executive Officer since 2008

MBA from Columbia University, MHL from Brown University

Diane C. Young

Celldex Therapeutics

Chief Medical Officer since 2019

MD from Harvard Medical School, AB in Biochemical Sciences from Harvard University

Findings from Research

In a phase Ib trial involving 26 patients with advanced PD-L1-positive ovarian cancer, pembrolizumab demonstrated a confirmed objective response rate of 11.5%, indicating some level of antitumor activity, with 1 complete response and 2 partial responses observed.

The treatment was generally well-tolerated, with 73.1% of patients experiencing treatment-related adverse events, but no deaths or treatment discontinuations due to these events, suggesting that pembrolizumab has a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab in patients with programmed death ligand 1-positive advanced ovarian cancer: Analysis of KEYNOTE-028. Varga, A., Piha-Paul, S., Ott, PA., et al.[2019]

In a study involving patients with recurrent platinum-resistant ovarian cancer, the combination of pembrolizumab, cisplatin, and gemcitabine resulted in an overall response rate of 60%, but the duration of response was relatively short at 4.9 months.

The addition of pembrolizumab did not show a significant benefit over chemotherapy alone, leading to the decision to close the trial for further accrual after an interim analysis indicated modest outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II trial of cisplatin, gemcitabine and pembrolizumab for platinum-resistant ovarian cancer. Walsh, CS., Kamrava, M., Rogatko, A., et al.[2022]

Bevacizumab, when combined with carboplatin and paclitaxel, significantly prolongs progression-free survival in women with newly diagnosed advanced ovarian cancer, as shown in the GOG-0218 and ICON7 studies.

In patients with recurrent platinum-sensitive ovarian cancer, bevacizumab combined with carboplatin and gemcitabine also extends progression-free survival, demonstrating its efficacy in both first-line and second-line treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bevacizumab combination therapy: a review of its use in patients with epithelial ovarian, fallopian tube, or primary peritoneal cancer. Dhillon, S.[2019]

In the PAOLA-1 study, older patients (aged ≥65 years) with newly diagnosed advanced ovarian cancer experienced significant progression-free survival (PFS) benefits from maintenance treatment with olaparib plus bevacizumab, achieving a median PFS of 21.6 months compared to 16.6 months with placebo (HR 0.55).

The safety profile of olaparib in older patients was comparable to that of younger patients, with no treatment-related deaths reported, although older patients did experience higher rates of hypertension and anemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of maintenance olaparib and bevacizumab in ovarian cancer patients aged ≥65 years from the PAOLA-1/ENGOT-ov25 trial. Sabatier, R., Rousseau, F., Joly, F., et al.[2023]

In a case study of a 44-year-old woman with advanced epithelial ovarian cancer, the combination of bevacizumab with carboplatin and paclitaxel chemotherapy resulted in complete remission after 6 cycles of treatment, demonstrating the efficacy of this regimen.

The treatment was well-tolerated, with no serious side effects such as bone marrow suppression, hypertension, or proteinuria reported during bevacizumab administration, suggesting a favorable safety profile for this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bevacizumab, Carboplatin and Paclitaxel Combination Treatment in Advanced Stage Ovarian Cancer: The First Experience in Thammasat University Hospital, Thailand: A Case Report. Suwannarurk, K., Thaweekul, Y., Mairaing, K., et al.[2018]

Bevacizumab, an anti-VEGF therapy, has shown efficacy in treating epithelial ovarian cancers, both as a standalone treatment and in combination with other therapies, based on evidence from Phase II trials involving various patient populations.

While most side effects of bevacizumab, such as proteinuria and hypertension, are mild and manageable, there are serious but rare risks like arterial thromboembolism and gastrointestinal perforation, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Experience with bevacizumab in the management of epithelial ovarian cancer. Burger, RA.[2015]

Bevacizumab, an anti-VEGF monoclonal antibody, has been shown to be effective in treating recurrent high-grade serous ovarian cancer, leading to its regulatory approval in many countries, including the US in 2014.

While bevacizumab is widely used and integrated into ovarian cancer treatment guidelines, it does not increase cure rates, highlighting the need for predictive biomarkers to better tailor treatments and weigh the benefits against costs and potential toxicities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-angiogenic agents in ovarian cancer: past, present, and future. Monk, BJ., Minion, LE., Coleman, RL.[2023]

Bevacizumab, a monoclonal antibody targeting vascular endothelial growth factor-A, has shown response rates of 16-21% as a single-agent treatment for recurrent ovarian cancer, indicating its efficacy in this context.

In combination with standard chemotherapy for advanced ovarian cancer, bevacizumab significantly improves progression-free survival, although it does not enhance overall survival; the main safety concern is hypertension, with rare but serious risks including gastrointestinal perforation and toxicity to the kidneys and central nervous system.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bevacizumab and ovarian cancer. Garcia, A., Singh, H.[2021]

The AURELIA trial demonstrated that adding bevacizumab to chemotherapy significantly improves progression-free survival (PFS) in patients with platinum-resistant recurrent ovarian cancer, with a median PFS of 8.1 months compared to 3.9 months for chemotherapy alone.

Independent review confirmed the primary findings, showing consistent results between investigator assessments and independent review committee evaluations, reinforcing the efficacy of bevacizumab in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Independent radiologic review of AURELIA, a phase 3 trial of bevacizumab plus chemotherapy for platinum-resistant recurrent ovarian cancer. Husain, A., Wang, Y., Hanker, LC., et al.[2022]

Bevacizumab has been shown to be effective in managing epithelial ovarian cancer, particularly when combined with cytotoxic chemotherapy, as indicated by phase III trial data that demonstrate improved progression-free survival.

There is a compelling argument for using bevacizumab as a single agent in patients with platinum-resistant ovarian cancer, suggesting a more rational and potentially cost-effective approach to treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The use of bevacizumab in the management of ovarian cancer: an argument for single-agent rather than combination therapy. Markman, M.[2020]

In a small case series of three patients with recurrent ovarian clear cell carcinoma (OCCC), the combination of lenvatinib and pembrolizumab resulted in a remarkable overall response rate of 100%.

Patients experienced progression-free survival ranging from 10 months to not-yet-reached, indicating that this treatment may be effective for those with platinum-resistant disease, although two patients ultimately succumbed to their illness after 14 and 27 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination lenvatinib plus pembrolizumab in the treatment of ovarian clear cell carcinoma: A case series. Calo, CA., Levine, MD., Brown, MD., et al.[2023]

References

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

Pembrolizumab in patients with programmed death ligand 1-positive advanced ovarian cancer: Analysis of KEYNOTE-028. [2019]

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

Phase II trial of cisplatin, gemcitabine and pembrolizumab for platinum-resistant ovarian cancer. [2022]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Bevacizumab combination therapy: a review of its use in patients with epithelial ovarian, fallopian tube, or primary peritoneal cancer. [2019]

4. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of maintenance olaparib and bevacizumab in ovarian cancer patients aged ≥65 years from the PAOLA-1/ENGOT-ov25 trial. [2023]

5. Thailand pubmed.ncbi.nlm.nih.gov

Bevacizumab, Carboplatin and Paclitaxel Combination Treatment in Advanced Stage Ovarian Cancer: The First Experience in Thammasat University Hospital, Thailand: A Case Report. [2018]

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

Experience with bevacizumab in the management of epithelial ovarian cancer. [2015]

7. England pubmed.ncbi.nlm.nih.gov

Anti-angiogenic agents in ovarian cancer: past, present, and future. [2023]

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

Bevacizumab and ovarian cancer. [2021]

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

Independent radiologic review of AURELIA, a phase 3 trial of bevacizumab plus chemotherapy for platinum-resistant recurrent ovarian cancer. [2022]

10. England pubmed.ncbi.nlm.nih.gov

The use of bevacizumab in the management of ovarian cancer: an argument for single-agent rather than combination therapy. [2020]

11. Netherlands pubmed.ncbi.nlm.nih.gov

Combination lenvatinib plus pembrolizumab in the treatment of ovarian clear cell carcinoma: A case series. [2023]