Pembrolizumab With Chemotherapy and MK-4830 for Treating Participants With Ovarian Cancer (MK-4830-002)

Study Overview
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Brief Summary
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The primary objective is to evaluate in participants with high-grade serous ovarian cancer (HGSOC), whether the reduction from baseline in circulating tumor DNA (ctDNA) at Cycle 3 (ΔctDNA) is larger in participants receiving MK-4830 + pembrolizumab in combination with standard of care (SOC) therapy than in those receiving pembrolizumab + SOC therapy.

Official Title
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A Randomized, Phase 2 Study of Pembrolizumab And Chemotherapy With or Without MK-4830 as Neoadjuvant Treatment for High-Grade Serous Ovarian Cancer

Conditions
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High-grade Serous Ovarian Carcinoma, Ovarian Carcinoma

Intervention / Treatment
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* Biological: Pembrolizumab
* Drug: Paclitaxel
* Drug: Carboplatin
* Biological: Avastin
* Biological: MK-4830
* Drug: Docetaxel


Participation Criteria
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Eligibility Criteria
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The main inclusion and exclusion criteria include but are not limited to the following: Inclusion Criteria: Has histologically-confirmed International Federation of Gynecology and Obstetrics (FIGO) Stage III or Stage IV HGSOC, primary peritoneal cancer, or fallopian tube cancer. Is a candidate for carboplatin and paclitaxel chemotherapy, to be administered in the neoadjuvant and adjuvant setting. Is a candidate for interval debulking surgery. Is able to provide archival tissue or newly obtained core, incisional, or excisional biopsy of a tumor lesion. Has adequate organ functions. Exclusion Criteria: Has a non-HGSOC histology. Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease. Has a known additional malignancy that is progressing or has required active treatment within the past 3 years. Has received prior treatment for any stage of OC, including radiation or systemic anticancer therapy. Planned or has been administered intraperitoneal chemotherapy as first-line therapy. Has received prior therapy with an anti-programmed cell death 1 protein (PD-1), anti-programmed cell death 1 ligand 1 (PD-L1), anti-programmed cell death 1 ligand 2 (PD-L2), anti-immunoglobulin-like transcript 4 (ILT4), or anti-human leukocyte antigen (HLA)-G agent or with an agent directed to another stimulatory or coinhibitory T-cell receptor. Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention. Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks before the first dose of study intervention. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study medication. Has known active Central Nervous System (CNS) metastases and/or carcinomatous meningitis. Has severe hypersensitivity to pembrolizumab, carboplatin, paclitaxel (or docetaxel, if applicable), Avastin or biosimilar (if using) and/or any of their excipients. Has an active autoimmune disease that has required systemic treatment in past 2 years. Has an active infection requiring systemic therapy. Has a known history of human immunodeficiency virus (HIV) infection. Has a known history of hepatitis B or known active hepatitis C virus infection. Has received colony-stimulating factors within 4 weeks prior to receiving study intervention on Day 1 of Cycle 1. Has had surgery <6 months prior to Screening to treat borderline ovarian tumors, early-stage OC, or early-stage fallopian tube cancer. Has a known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study. Has current, clinically relevant bowel obstruction. Has a history of hemorrhage, hemoptysis, or active gastrointestinal (GI) bleeding within 6 months prior to randomization. Has uncontrolled hypertension. Has had an allogenic tissue/solid organ transplant. .Has either had major surgery within 3 weeks of randomization or has not recovered from any effects of any major surgery.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pembrolizumab + Standard of Care (SOC) + MK-4830<br>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. | Biological: Pembrolizumab<br>* 200 mg by IV infusion on Day 1 of each 21-day cycle<br>* Other names: KEYTRUDA®;Drug: Paclitaxel<br>* 175 mg/m^2 by IV infusion on Day 1 of each 21-day cycle<br>* Other names: TAXOL®;Drug: Carboplatin<br>* AUC 5 to 6 by IV infusion on Day 1 of each 21-day cycle<br>* Other names: PARAPLATIN®;Biological: Avastin<br>* According to local practice and at the choice of the investigator.<br>* Other names: Avegra;Biological: MK-4830<br>* 800 mg by IV infusion on Day 1 of each 21-day cycle<br>Drug: Docetaxel<br>* 75 mg/m^2 by IV infusion on Day 1 of each 21-day cycle<br>|
| Active Comparator: Pembrolizumab + SOC<br>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. | Biological: Pembrolizumab<br>* 200 mg by IV infusion on Day 1 of each 21-day cycle<br>* Other names: KEYTRUDA®;Drug: Paclitaxel<br>* 175 mg/m^2 by IV infusion on Day 1 of each 21-day cycle<br>* Other names: TAXOL®;Drug: Carboplatin<br>* AUC 5 to 6 by IV infusion on Day 1 of each 21-day cycle<br>* Other names: PARAPLATIN®;Biological: Avastin<br>* According to local practice and at the choice of the investigator.<br>* Other names: Avegra;Drug: Docetaxel<br>* 75 mg/m^2 by IV infusion on Day 1 of each 21-day cycle<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in Circulating Tumor Deoxyribonucleic Acid (ctDNA) | Change from baseline in circulating tumor deoxyribonucleic acid (ctDNA). | Baseline and Week 7 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in Neoadjuvant ctDNA | Change from baseline in neoadjuvant ctDNA. | Baseline and Week 7 | 
| Pathological Complete Response (pCR) Rate | Percentage of participants with all surgical specimens collected during the interval debulking surgery that are microscopically negative for residual tumor by logistic regression modeling of pathological Complete Response (pCR). | Up to approximately 12 weeks | 
| Chemotherapy Response Score (CRS) | Percentage of participants with residual disease assessed by logistic regression modeling of chemotherapy response score (CRS). CRS is a 3-tiered scoring system (CRS 1-3) based on the pathological analysis of surgically removed omental masses, with CRS3 (complete or near-complete response) characterized by the lack of residual tumor cells in the omentum or presence of tumor foci up to 2 mm maximum size. A binary response of CRS3 (no residual disease) vs. non-CRS3 (residual disease) will be assessed. | Up to approximately 12 Weeks | 
| Number of Participants Who Experienced an Adverse Event (AE) | An AE was any untoward medical occurrence in a participant administered study drug, which does not necessarily have to have a causal relationship with the study drug. | Up to approximately 40 Weeks | 
| Number of Participants Who Discontinued Study Treatment Due to an AE | An AE was any untoward medical occurrence in a participant administered study drug which does not necessarily have to have a causal relationship with the study drug. | Up to approximately 28 Weeks |