Pembrolizumab + Paclitaxel +/- Bevacizumab for Ovarian Cancer

Not currently recruiting at 223 trial locations

Overseen By Toll Free Number

Age: 18+

Sex: Female

Trial Phase: Phase 3

Sponsor: Merck Sharp & Dohme Corp.

Must be taking: Paclitaxel, Bevacizumab

Must not be taking: Steroids, Immunosuppressants

Disqualifiers: Immunodeficiency, CNS metastases, Autoimmune, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: 3

Duration: Approximately 2 years

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, involving pembrolizumab (an immunotherapy drug) and paclitaxel (a chemotherapy drug), with or without bevacizumab (also known as Avastin, an anti-angiogenesis drug). The researchers aim to determine if these combinations can delay cancer progression compared to standard treatments. Participants with ovarian, fallopian tube, or primary peritoneal cancer that has worsened after platinum-based chemotherapy might be suitable candidates. As a Phase 3 trial, this study represents the final step before potential FDA approval, offering participants a chance to contribute to a promising treatment's journey toward becoming widely available.

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 have received certain treatments like systemic anticancer therapy or radiation therapy 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 has shown that the combination of pembrolizumab and paclitaxel, with or without bevacizumab, is generally well-tolerated by patients. One study found that this combination helped ovarian cancer patients live longer without disease progression and had manageable side effects.

Patients who previously received pembrolizumab and paclitaxel experienced mostly mild to moderate side effects. Common side effects included tiredness, nausea, and hair loss, which are typical with chemotherapy. Adding bevacizumab did not significantly increase severe side effects.

This treatment is currently in a late-stage trial, indicating substantial information about its safety. The FDA has already approved pembrolizumab for other types of cancer, further supporting its safety profile. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for ovarian cancer because they combine pembrolizumab, an immunotherapy drug, with paclitaxel, a chemotherapy agent, and potentially bevacizumab, which targets blood vessel growth in tumors. Unlike traditional chemotherapy alone, pembrolizumab boosts the immune system to recognize and attack cancer cells, offering a potentially more precise approach. Additionally, bevacizumab can limit the blood supply to the tumor, potentially enhancing treatment effectiveness. This multi-faceted approach could lead to better outcomes by attacking the cancer on several fronts.

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

In this trial, participants will receive either a combination of pembrolizumab, paclitaxel, and possibly bevacizumab, or a placebo with paclitaxel and possibly bevacizumab. Research has shown that combining pembrolizumab, paclitaxel, and bevacizumab may help treat ovarian cancer. One study found that this combination reduced the risk of cancer progression or death in patients whose cancer recurred and did not respond to standard treatments. Additionally, data indicated that patients lived longer with this treatment. Pembrolizumab with chemotherapy has also proven effective for advanced ovarian cancer without causing serious side effects. Overall, these findings suggest that this combination treatment might be more effective than standard chemotherapy alone for some ovarian cancer patients. ^{1 2 6 7 8}

Who Is on the Research Team?

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Are You a Good Fit for This Trial?

This trial is for individuals with certain types of ovarian cancer who have had 1-2 previous treatments including platinum-based therapy but are now resistant to it. They must be able to undergo chemotherapy, not be pregnant or breastfeeding, and use effective contraception if applicable. People can't join if they've had recent bleeding issues, other active cancers within 3 years, severe allergies to the drugs being tested, uncontrolled high blood pressure, or infections requiring systemic treatment.

Inclusion Criteria

My cancer worsened within 6 months after my last platinum-based chemotherapy.

I am eligible for paclitaxel chemotherapy.

Has provided documented informed consent for the study.

Exclusion Criteria

My cancer got worse during or right after my first platinum-based treatment.

I have not had cancer treatment or experimental drugs in the last 4 weeks.

I had radiation therapy less than 2 weeks ago.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive pembrolizumab or placebo plus paclitaxel with or without bevacizumab for up to 18 cycles (approximately 2 years)

Approximately 2 years

Visits every 3 weeks for paclitaxel administration

Follow-up

Participants are monitored for progression-free survival and overall survival

Up to 64 months

What Are the Treatments Tested in This Trial?

Interventions

• Bevacizumab
• Paclitaxel
• Pembrolizumab

Trial Overview

The study aims to see if adding Pembrolizumab (an immunotherapy drug) to Paclitaxel chemotherapy (with or without Bevacizumab) improves progression-free survival compared to a placebo plus the same chemo regimen in patients with PD-L1 positive tumors and all participants.

How Is the Trial Designed?

Group I: Pembrolizumab + paclitaxel ± bevacizumab Experimental Treatment 4 Interventions

Participants receive pembrolizumab 400 mg via intravenous (IV) infusion for eighteen 6-week cycles (approximately 2 years) PLUS paclitaxel 80 mg/m\^2 via IV infusion on Days 1, 8, and 15 of each 3-week cycle until intolerance or disease progression. Participants who experience severe hypersensitivity reaction to paclitaxel or an AE requiring discontinuation of paclitaxel may receive docetaxel (75 mg/m\^2 every 3 weeks \[Q3W\]) after Sponsor consultation. Participants may also receive bevacizumab 10 mg/kg via IV infusion of each 2-week cycle until intolerance, disease progression, or at the Investigator's discretion.

Group II: Placebo + paclitaxel ± bevacizumab Placebo Group 4 Interventions

Participants receive placebo via IV infusion for eighteen 6-week cycles (approximately 2 years) PLUS paclitaxel 80 mg/m\^2 via IV infusion on Days 1, 8, and 15 of each 3-week cycle until intolerance or disease progression. Participants who experience severe hypersensitivity reaction to paclitaxel or an AE requiring discontinuation of paclitaxel may receive docetaxel (75 mg/m\^2 every 3 weeks \[Q3W\]) after Sponsor consultation. Participants may also receive bevacizumab 10 mg/kg via IV infusion of each 2-week cycle until intolerance, disease progression, or at the Investigator's discretion.

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

Approved in United States as Taxol for:

• Ovarian cancer
• Breast cancer
• Non-small cell lung cancer
• Kaposi's sarcoma

Approved in European Union as Taxol for:

• Ovarian cancer
• Breast cancer
• Non-small cell lung cancer
• Kaposi's sarcoma

Approved in Canada as Paclitaxel for:

• Ovarian cancer
• Breast cancer
• Non-small cell lung cancer
• Kaposi's sarcoma

Who Is Running the Clinical Trial?

Merck Sharp & Dohme Corp.

Lead Sponsor

Trials

2,287

Recruited

4,582,000+

Chirfi Guindo

Merck Sharp & Dohme Corp.

Chief Medical Officer

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

Robert M. Davis

Merck Sharp & Dohme Corp.

Chief Executive Officer since 2021

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

Merck Sharp & Dohme LLC

Lead 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

Published Research Related to This Trial

Paclitaxel has recently become a standard chemotherapy treatment for advanced ovarian cancer, especially when combined with platinum compounds, based on a large randomized trial by the Gynaecologic Oncology Group.

Ongoing clinical trials are investigating the optimal use of paclitaxel, including its dosage, administration schedule, and comparing the effectiveness and side effects of different platinum combinations (carboplatin vs. cisplatin).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

USA update on paclitaxel in ovarian cancer. Ozols, RF.[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]

Paclitaxel is an effective treatment for treatment-refractory ovarian cancer, working by stabilizing microtubules to induce cytotoxicity, despite facing challenges like severe hypersensitivity reactions and formulation issues.

The drug is associated with significant side effects, including myelosuppression, mucositis, and neurotoxicity, which are dose-dependent, highlighting the need for careful management in clinical use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel (taxol). Kohler, DR., Goldspiel, BR.[2019]

The combination of docetaxel, oxaliplatin, and bevacizumab as a first-line treatment for advanced ovarian, peritoneal, or fallopian tube cancer showed a promising 12-month progression-free survival rate of 65.7% among 132 patients, with a median progression-free survival of 16.3 months.

The treatment was generally safe, with the most common severe side effects being neutropenia and leukopenia, and only one reported fatal gastrointestinal perforation, indicating no unexpected safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II trial of oxaliplatin, docetaxel, and bevacizumab as first-line therapy of advanced cancer of the ovary, peritoneum, and fallopian tube. Herzog, TJ., Monk, BJ., Rose, PG., et al.[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 the GOG-0218 phase III trial involving 751 patients with advanced epithelial ovarian cancer, the addition of bevacizumab to standard chemotherapy significantly improved progression-free survival (PFS) but did not extend overall survival (OS).

High levels of the inflammatory cytokine IL6 were predictive of a therapeutic benefit from bevacizumab, with patients showing longer PFS (14.2 months vs. 8.7 months) and OS (39.6 months vs. 33.1 months) compared to those receiving placebo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Predictive Blood-Based Biomarkers in Patients with Epithelial Ovarian Cancer Treated with Carboplatin and Paclitaxel with or without Bevacizumab: Results from GOG-0218. Alvarez Secord, A., Bell Burdett, K., Owzar, K., et al.[2023]

In a study of 90 ovarian cancer patients, the combination of bevacizumab with paclitaxel and carboplatin significantly improved treatment outcomes, with higher remission and disease control rates compared to those receiving only paclitaxel and carboplatin.

The combined treatment also led to lower levels of tumor markers CA199, CEA, and CA242 without increasing the risk of adverse effects, indicating it is a safe and effective option for improving patient prognosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of bevacizumab plus paclitaxel and carboplatin regimen on prognostic survival of ovarian cancer patients. Jiang, Q., Qian, H., Mei, L., et al.[2023]

Paclitaxel, a novel antineoplastic drug, has shown significant effectiveness in treating advanced cancers such as ovarian, breast, non-small cell lung cancer, and head and neck cancer, with a potential to become a first-line treatment when combined with platinum for advanced ovarian cancer.

While initial hypersensitivity reactions posed challenges, current premedication strategies have reduced these side effects to less than 3%, although neutropenia remains a major dose-limiting adverse effect.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel (Taxol): a review of its antitumor activity in clinical studies Minireview. Hájek, R., Vorlicek, J., Slavik, M.[2015]

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 study of 164 patients with recurrent ovarian cancer, the combination of bevacizumab (BEV) with paclitaxel and carboplatin significantly improved progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) compared to the control group receiving only paclitaxel and carboplatin.

The experimental group experienced fewer adverse reactions, such as allergies and gastrointestinal issues, and showed a significant improvement in quality of life after treatment, indicating that BEV combined with paclitaxel is both effective and safer for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic effect of bevacizumab combined with paclitaxel and carboplatin on recurrent ovarian cancer. Cong, J., Liu, R., Hou, J., et al.[2020]

In a study of 51 patients with recurrent epithelial ovarian cancer, the combination of weekly paclitaxel and biweekly bevacizumab showed a high overall response rate of 60%, with a median progression-free survival of 7 months and median overall survival of 12 months.

The treatment was found to have an acceptable toxicity profile, with the most severe side effects being fatigue (16%), hematologic issues (9%), and neurotoxicity (7%), indicating that while effective, careful monitoring for side effects is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sustained progression-free survival with weekly paclitaxel and bevacizumab in recurrent ovarian cancer. Hurt, JD., Richardson, DL., Seamon, LG., et al.[2015]

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