Pembrolizumab + Chemotherapy + MK-4830 for Ovarian Cancer

Recruiting at 45 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

160 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing whether adding MK-4830 to pembrolizumab and standard treatments helps patients with a severe type of ovarian cancer. The goal is to see if this combination reduces cancer cells in the blood more effectively than just using pembrolizumab with standard treatments. The medications work by boosting the immune system to fight cancer.

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.

What data supports the effectiveness of the drug combination of Pembrolizumab, Chemotherapy, and MK-4830 for ovarian cancer?

Research shows that combining docetaxel with carboplatin is effective for ovarian cancer, with a response rate of 67% and better tolerance compared to other combinations. Docetaxel is also effective in cases resistant to other treatments, making it a promising option in combination therapies. ^{1 2 3 4 5}

What safety data exists for the combination of Pembrolizumab, Chemotherapy, and MK-4830 in treating ovarian cancer?

The combination of docetaxel and carboplatin, which are part of the chemotherapy regimen, has been studied for ovarian cancer and is generally considered safe, though it can cause side effects like bone marrow suppression (reduced blood cell production) and hypersensitivity reactions. These side effects are manageable with medications like G-CSF (a drug that helps the body make more white blood cells). ^{2 4 5 6 7}

What makes the drug combination of Pembrolizumab, Chemotherapy, and MK-4830 unique for ovarian cancer?

This treatment combines pembrolizumab, an immune therapy that helps the body's immune system recognize and attack cancer cells, with chemotherapy drugs like carboplatin and paclitaxel, which kill cancer cells directly. The addition of MK-4830, a novel component, may enhance the immune response, making this combination potentially more effective for ovarian cancer compared to standard treatments. ^{8 9 10 11 12}

Research Team

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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, carboplatin Area Under the Curve (AUC) 5 to 6, (or docetaxel 75 mg/m\^2), and MK-4830 800 mg by intravenous (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, carboplatin AUC 5 to 6, (or docetaxel 75 mg/m\^2), MK-4830 800 mg, and avastin (or biosimilar) 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, carboplatin AUC 5 to 6 and (or docetaxel 75 mg/m\^2) 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, carboplatin AUC 5 to 6, (or docetaxel 75 mg/m\^2) and avastin (or biosimilar) 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

Findings from Research

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]

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]

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 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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Progress in the treatment of ovarian cancer. Scottish Gynaecological Cancer Trials Group. [2019]

2. 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]

3. United States 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. [2018]

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

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

5. England pubmed.ncbi.nlm.nih.gov

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

6. Japan pubmed.ncbi.nlm.nih.gov

[Docetaxel and carboplatin for epithelial ovarian cancer]. [2018]

7. Germany pubmed.ncbi.nlm.nih.gov

A multicenter phase II study of cisplatin and docetaxel (Taxotere) in the first-line treatment of advanced ovarian cancer: a GINECO study. [2018]

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

Molecular determinants of clinical outcomes of pembrolizumab in recurrent ovarian cancer: Exploratory analysis of KEYNOTE-100. [2023]

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

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

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

Pembrolizumab in combination with bevacizumab and oral cyclophosphamide in heavily pre-treated platinum-resistant ovarian cancer. [2023]

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

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

12. England 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. [2022]