Pembrolizumab + Paclitaxel +/- Bevacizumab for Ovarian Cancer

Recruiting at 190 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

616 Participants Needed

Trial Summary

What is the purpose of this trial?

The primary objective is to compare pembrolizumab plus paclitaxel with or without bevacizumab to placebo plus paclitaxel with or without bevacizumab, with respect to progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as assessed by the investigator. The hypotheses are that pembrolizumab plus paclitaxel with or without bevacizumab is superior to placebo plus paclitaxel with or without bevacizumab, with respect to PFS per RECIST 1.1 as assessed by the investigator for participants with programmed cell death ligand 1 (PD-L1) positive tumors (Combined Positive Score \[CPS\] ≥1) and that pembrolizumab plus paclitaxel with or without bevacizumab is superior to placebo plus paclitaxel with or without bevacizumab, with respect to PFS per RECIST 1.1 as assessed by the investigator for all participants.

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.

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

Research shows that combining bevacizumab with paclitaxel improves progression-free survival (the time during and after treatment that a patient lives with the disease without it getting worse) in ovarian cancer patients, although it does not extend overall survival. This suggests that the combination can help control the disease for a longer period. ^{1 2 3 4 5}

Is the combination of Pembrolizumab, Paclitaxel, and Bevacizumab safe for humans?

Paclitaxel, used in combination with other drugs, has been shown to cause side effects like hypersensitivity reactions, neutropenia (low white blood cell count), and neurotoxicity (nerve damage). Bevacizumab combined with Paclitaxel has been studied for safety in ovarian cancer, but specific safety data for Pembrolizumab in this combination is not provided in the available research. ^{6 7 8 9 10}

What makes the drug combination of Pembrolizumab, Paclitaxel, and Bevacizumab unique for treating ovarian cancer?

This drug combination is unique because it combines Pembrolizumab, an immunotherapy that helps the immune system attack cancer cells, with Paclitaxel, a chemotherapy that stops cancer cell growth, and optionally Bevacizumab, which inhibits blood vessel growth in tumors. This multi-faceted approach targets ovarian cancer from different angles, potentially offering benefits over standard treatments. ^{3 11 12 13 14}

Research Team

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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 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]

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]

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]

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]

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]

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 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]

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]

References

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

Effect of bevacizumab plus paclitaxel and carboplatin regimen on prognostic survival of ovarian cancer patients. [2023]

2. United States 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. [2023]

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

Phase II clinical trial of bevacizumab with albumin-bound paclitaxel in patients with recurrent, platinum-resistant primary epithelial ovarian or primary peritoneal carcinoma. [2020]

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

Sustained progression-free survival with weekly paclitaxel and bevacizumab in recurrent ovarian cancer. [2015]

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

Evaluation of the antitumor activity of NOV202, a novel microtubule targeting and vascular disrupting agent. [2018]

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

A phase II study of cetuximab/paclitaxel/carboplatin for the initial treatment of advanced-stage ovarian, primary peritoneal, or fallopian tube cancer. [2022]

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

USA update on paclitaxel in ovarian cancer. [2019]

8. Slovakia pubmed.ncbi.nlm.nih.gov

Paclitaxel (Taxol): a review of its antitumor activity in clinical studies Minireview. [2015]

9. Cyprus pubmed.ncbi.nlm.nih.gov

Therapeutic effect of bevacizumab combined with paclitaxel and carboplatin on recurrent ovarian cancer. [2020]

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

Paclitaxel (taxol). [2019]

11. 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]

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

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

13. United States 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. [2021]

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

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