Pembrolizumab + Chemotherapy + MK-4830 for Ovarian Cancer

No longer recruiting at 56 trial locations

Overseen By Toll Free Number

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: Merck Sharp & Dohme LLC

Must be taking: Carboplatin, Paclitaxel

Must not be taking: Steroids, Immunosuppressants

Disqualifiers: Non-HGSOC, Active infection, Autoimmune, 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

Compensation: Varies

Number of Visits: 6

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug combination for high-grade serous ovarian cancer (HGSOC), examining whether adding MK-4830 (an experimental treatment) can enhance treatment outcomes. Participants will receive standard chemotherapy drugs, with or without MK-4830. The trial aims to determine if this combination more effectively reduces cancer DNA in the blood. It seeks individuals with advanced ovarian, peritoneal, or fallopian tube cancer who have not yet received treatment and plan to undergo surgery. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are on chronic systemic steroid therapy or any form of immunosuppressive therapy, you may need to stop or adjust it, as these are part of the exclusion criteria.

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

Research shows that pembrolizumab combined with MK-4830 generally has a manageable safety profile. In a previous study, participants taking these two drugs together experienced some side effects, but these were usually easy to handle. The study also found that this drug combination helped fight cancer cells.

Pembrolizumab is already approved for other uses, indicating its relative safety. MK-4830 remains under investigation, but early results appear promising for safety. These findings come from an early study, so further research is necessary to fully understand the safety of these treatments. ^{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, a powerful immunotherapy drug, with chemotherapy and the novel agent MK-4830. Unlike standard treatments that primarily rely on chemotherapy drugs like carboplatin and paclitaxel, this approach uses pembrolizumab to help the immune system recognize and attack cancer cells more effectively. MK-4830 is a unique addition that targets a specific immune checkpoint, potentially enhancing the immune response against the tumor. This innovative combination has the potential to improve outcomes by not only attacking the cancer directly with chemotherapy but also by boosting the body's natural defenses.

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

Research shows that combining pembrolizumab with chemotherapy may be promising for treating high-grade serous ovarian cancer (HGSOC). In this trial, one group of participants will receive pembrolizumab with standard chemotherapy, while another group will receive pembrolizumab, standard chemotherapy, and an additional drug called MK-4830. Previous studies found that adding MK-4830 to this combination was safe and showed potential in fighting the cancer. This treatment might also lower levels of circulating tumor DNA, indicating that the cancer is shrinking. Specifically, another study found that patients who received pembrolizumab with chemotherapy lived longer over 12 months compared to those who did not. These findings suggest that this treatment combination could be effective for ovarian cancer. ^{1 2 3 4 6}

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 advanced ovarian cancer who can undergo chemotherapy and surgery, have adequate organ function, and can provide a tumor biopsy. It's not for those who've had certain recent treatments or vaccines, active infections including HIV or hepatitis B/C, other cancers within 3 years, prior ovarian cancer treatment, uncontrolled blood pressure, severe allergies to study drugs or their ingredients.

Inclusion Criteria

I am eligible for surgery to remove as much cancer as possible.

My cancer is advanced ovarian, peritoneal, or fallopian tube cancer.

I can provide a sample of my tumor for testing.

Exclusion Criteria

I have cancer that has spread to my brain or spinal cord.

I am receiving or will receive chemotherapy directly into my abdomen as my first treatment.

I have not received a live vaccine in the last 30 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Treatment

Participants receive pembrolizumab and chemotherapy with or without MK-4830 before surgery for 3 cycles, each cycle lasting 21 days

9 weeks

3 visits (in-person)

Post-Surgery Treatment

Participants receive pembrolizumab, chemotherapy, and avastin (or biosimilar) with or without MK-4830 after surgery for 3 cycles, each cycle lasting 21 days

9 weeks

3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Carboplatin
• Docetaxel
• MK-4830
• Paclitaxel
• Pembrolizumab

Trial Overview

The trial tests if adding MK-4830 to pembrolizumab (an immunotherapy drug) plus standard chemo works better than just pembrolizumab with chemo in reducing tumor DNA in the blood after three cycles of treatment in patients with high-grade serous ovarian cancer.

How Is the Trial Designed?

Group I: Pembrolizumab + Standard of Care (SOC) + MK-4830 Experimental Treatment 6 Interventions

Before surgery participants will receive pembrolizumab 200 mg, paclitaxel 175 mg/m\^2 (or docetaxel 75 mg/m\^2), carboplatin Area Under the Curve (AUC) 5 to 6, and MK-4830 800 mg by intravenous (IV) infusion on Day 1 of each 21-day cycle (every 3 weeks \[Q3W\]) for 3 cycles. After surgery participants will receive pembrolizumab 200 mg, paclitaxel 175 mg/m\^2 (or docetaxel 75 mg/m\^2), carboplatin AUC 5 to 6, and MK-4830 800 mg (with avastin \[or biosimilar\] at the investigator's discretion and per insitutional guidelines) by IV infusion on Day 1 of each 21-day cycle (Q3W) for 3 cycles.

Group II: Pembrolizumab + SOC Active Control 5 Interventions

Before surgery participants will receive pembrolizumab 200 mg, paclitaxel 175 mg/m\^2 (or docetaxel 75 mg/m\^2), and carboplatin AUC 5 to 6 by IV infusion on Day 1 of each 21-day cycle (Q3W) for 3 cycles. After surgery participants will receive pembrolizumab 200 mg, paclitaxel 175 mg/m\^2 (or docetaxel 75 mg/m\^2), and carboplatin AUC 5 to 6 (with avastin \[or biosimilar\] at the investigator's discretion and per insitutional guidelines) by IV infusion on Day 1 of each 21-day cycle (Q3W) for 3 cycles.

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

Approved in United States as Paraplatin for:

• Ovarian cancer
• Testicular cancer
• Lung cancer
• Head and neck cancer
• Brain cancer

Approved in European Union as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer

Approved in Canada as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer
• Testicular cancer

Who Is Running the Clinical Trial?

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

The combination of pembrolizumab and carboplatin was found to be well-tolerated and showed activity in patients with recurrent platinum-resistant ovarian cancer, with a median overall survival of 11.3 months.

Patients with a higher ratio of peripheral CD8+PD1+Ki67+ T cells to tumor burden had significantly longer overall survival, suggesting this ratio could help identify those who may benefit more from this treatment approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab with low-dose carboplatin for recurrent platinum-resistant ovarian, fallopian tube, and primary peritoneal cancer: survival and immune correlates. Liao, JB., Gwin, WR., Urban, RR., et al.[2022]

Docetaxel combined with carboplatin is a feasible and tolerable first-line treatment option for newly diagnosed epithelial ovarian cancer, showing no significant difference in progression-free or overall survival compared to the traditional paclitaxel and carboplatin combination in a study of 1,077 patients.

While docetaxel was associated with more myelosuppression, it resulted in fewer cases of neuropathy compared to paclitaxel, leading to better quality-of-life outcomes for patients receiving docetaxel.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of docetaxel in the treatment of newly diagnosed advanced ovarian cancer. Vasey, PA.[2018]

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]

Docetaxel shows comparable efficacy to paclitaxel in treating ovarian cancer, with a median progression-free survival of 16 months and a low neurotoxicity rate of 5%, significantly lower than the over 30% seen with paclitaxel.

In a large randomized trial involving 1077 patients, docetaxel combined with carboplatin demonstrated acceptable toxicity and treatment adherence, justifying further analysis of its safety and efficacy compared to the traditional paclitaxel-carboplatin regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The integration of docetaxel into first-line chemotherapy for ovarian cancer. Kaye, SB.[2019]

In a study of 317 patients with advanced recurrent ovarian cancer treated with pembrolizumab, no significant associations were found between gene expression signatures and clinical outcomes, indicating that these markers may not be reliable predictors of treatment response.

However, higher densities of specific myeloid cell phenotypes (CD11c+ and CD11c+/MHCII-/CD163-/CD68-) in the tumor microenvironment were positively associated with better outcomes, suggesting that these immune cell populations could play a role in enhancing the efficacy of pembrolizumab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Molecular determinants of clinical outcomes of pembrolizumab in recurrent ovarian cancer: Exploratory analysis of KEYNOTE-100. Ledermann, JA., Shapira-Frommer, R., Santin, AD., et al.[2023]

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 carboplatin and docetaxel shows high efficacy in treating advanced ovarian cancer, with an 81% objective response rate among assessable patients in a phase II trial involving 50 participants.

While the treatment is associated with significant toxicity, particularly grade 4 neutropenia in 64% of patients, hypersensitivity reactions were common but manageable, allowing most patients to continue therapy without interruption.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination chemotherapy with carboplatin and docetaxel in the treatment of cancers of the ovary and fallopian tube and primary carcinoma of the peritoneum. Markman, M., Kennedy, A., Webster, K., et al.[2018]

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The purpose of this study is to evaluate whether the reduction from baseline in circulating tumor DNA at Cycle 3 (ΔctDNA) is larger in participants receiving MK ...