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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of treatments for ovarian cancer that has returned after previous treatments. It examines the effectiveness of two drugs, pembrolizumab and bevacizumab (also known as Avastin), and whether adding a third drug, CDX-1140, can help shrink tumors. The trial aims to determine if this combination can reduce symptoms, improve survival, and enhance the quality of life for patients. Ideal participants are those with recurrent ovarian cancer who have undergone up to four previous treatments and know their BRCA gene status. 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 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.

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

Research shows that the combination of pembrolizumab and bevacizumab is generally well-tolerated. In one study, 47.5% of patients responded well to the treatment, with most not experiencing severe side effects. Another report found that adding pembrolizumab to bevacizumab and other drugs did not increase serious side effects, suggesting it is safe for most patients.

Less detailed safety information exists for adding anti-CD40 CDX-1140 to pembrolizumab and bevacizumab. However, this trial is in an early phase, primarily focusing on safety and tolerability. Early-phase trials aim to ensure treatments do not cause unacceptable side effects, so participants receive close monitoring.

In summary, existing research supports the safety of pembrolizumab and bevacizumab, and ongoing trials are assessing the safety of adding anti-CD40 CDX-1140. Participants in these trials are closely monitored to manage any potential side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of pembrolizumab and bevacizumab for ovarian cancer because these treatments work in a unique way compared to standard options like chemotherapy. Pembrolizumab is an immunotherapy that enhances the body's immune response to target cancer cells, while bevacizumab is an anti-angiogenic drug that cuts off the blood supply tumors need to grow. The addition of CDX-1140 in one of the treatment arms is particularly intriguing, as it is designed to further activate the immune system against cancer. This combination has the potential to provide a more effective and targeted approach to treating ovarian cancer, which could lead to better outcomes for patients.

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

Research has shown that using pembrolizumab and bevacizumab together may help treat recurrent ovarian cancer. Studies have found that this combination can shrink tumors in up to 48% of patients, meaning nearly half experienced a reduction in tumor size. In this trial, some participants will receive this combination. Another group will receive pembrolizumab, bevacizumab, and CDX-1140. Adding CDX-1140, which boosts immune cells, might enhance these effects. Early results suggest that using CDX-1140 with pembrolizumab and bevacizumab could improve symptoms, extend survival, and enhance quality of life. ^{1 3 5 6 7}

Who Is on the Research Team?

Emese Zsiros

Principal Investigator

Roswell Park Cancer Institute

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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 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]

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]

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]

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]

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]

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, 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, 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]

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]

Citations

1. merck.com merck.com/news/keytruda-pembrolizumab-plus-chemotherapy-with-or-without-bevacizumab-reduced-risk-of-disease-progression-or-death-versus-chemotherapy-with-or-without-bevacizumab-in-certain-patients-with-plati/

KEYTRUDA® (pembrolizumab) Plus Chemotherapy With ... “Results from KEYNOTE-B96 have the potential to mark a significant step forward in the treatment of platinum-resistant recurrent ovarian cancer ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12271593/

Efficacy of pembrolizumab in combination with ... The combination of pembrolizumab, bevacizumab, and oral metronomic cyclophosphamide was well tolerated and demonstrated a 21.1 percent response rate.

3. jamanetwork.com jamanetwork.com/journals/jamaoncology/fullarticle/2773114

Efficacy and Safety of Pembrolizumab in Combination With ... The combination of pembrolizumab with bevacizumab and oral cyclophosphamide was well tolerated and demonstrated clinical benefit in 95.0% and durable treatment ...

4. targetedonc.com targetedonc.com/view/pembrolizumab-bevacizumab-achieves-nearly-48-orr-in-recurrent-ovarian-cancer

Pembrolizumab/Bevacizumab Achieves Nearly 48% ORR ... Pembrolizumab and bevacizumab combination shows efficacy in recurrent epithelial ovarian cancer, particularly in clear cell subtype, with a 41.7 ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT06083844

NCT06083844 | Phase II Investigation of Pembrolizumab in ... To determine whether the combination of pembrolizumab, bevacizumab (or equivalent biosimilars) and oral low dose cyclophosphamide can improve PFS by 6 months ( ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S2352578925001183

Efficacy of pembrolizumab in combination with ... The combination of pembrolizumab, bevacizumab, and oral metronomic cyclophosphamide was well tolerated and demonstrated a 21.1 percent response rate.

7. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.5590

A comparative study of the real-world safety and ... The addition of pembrolizumab to metronomic cyclophosphamide and bevacizumab was not associated with an improved response rate, PFS, or OS.