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

Phase 2

Completed

Conditions: High-grade Serous Ovarian Carcinoma
Ovarian Carcinoma

Interventions: Biological: Pembrolizumab
Drug: Paclitaxel
Drug: Carboplatin
Biological: Avastin
Biological: MK-4830
Drug: Docetaxel

Registration Number: NCT05446870

Lead Sponsor: Merck Sharp & Dohme LLC

Brief Summary: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: Female

Target Recruitment: 160

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Pembrolizumab + SOC	Avastin	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.
Pembrolizumab + Standard of Care (SOC) + MK-4830	Pembrolizumab	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.
Pembrolizumab + Standard of Care (SOC) + MK-4830	Avastin	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.
Pembrolizumab + Standard of Care (SOC) + MK-4830	MK-4830	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.
Pembrolizumab + SOC	Pembrolizumab	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.
Pembrolizumab + Standard of Care (SOC) + MK-4830	Carboplatin	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.
Pembrolizumab + Standard of Care (SOC) + MK-4830	Paclitaxel	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.
Pembrolizumab + SOC	Docetaxel	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.
Pembrolizumab + Standard of Care (SOC) + MK-4830	Docetaxel	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.
Pembrolizumab + SOC	Paclitaxel	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.
Pembrolizumab + SOC	Carboplatin	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.

Primary Outcome Measures

Name	Time	Method
Change From Baseline in Circulating Tumor Deoxyribonucleic Acid (ctDNA)	Baseline and Week 7	Blood samples were collected to determine levels of ctDNA. The fold change in the mean mutant/tumor molecules per mL (MTM/mL) at Cycle 3 from baseline is presented.

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in Neoadjuvant ctDNA	Baseline and Week 7	Change from baseline in neoadjuvant ctDNA.
Pathological Complete Response (pCR) Rate	Up to approximately 12 weeks	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).
Chemotherapy Response Score (CRS)	Up to approximately 12 Weeks	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.
Number of Participants Who Experienced an Adverse Event (AE)	Up to approximately 40 Weeks	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.
Number of Participants Who Discontinued Study Treatment Due to an AE	Up to approximately 28 Weeks	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.

Trial Locations

Locations (45): Changhua Christian Hospital-Obstetrics and Gynecology ( Site 1203)
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Changhua County, Changhua, Taiwan
Hospital Universitari Vall d'Hebron-Departamento de Oncologia- VHIO ( Site 1101)
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Barcelona, Spain
Hospital Universitario 12 de Octubre-Medical Oncology ( Site 1104)
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Madrid, Madrid, Comunidad De, Spain
University of Colorado Anschutz Medical Campus-Cancer Clinical Trials Office ( Site 0108)
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Aurora, Colorado, United States
Shaare Zedek Medical Center ( Site 0601)
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Jerusalem, Israel
Istituto Europeo di Oncologia IRCCS-Divisione di Ginecologia Oncologica ( Site 0501)
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Milano, Italy
Swietokrzyskie Centrum Onkologii, Samodzielny Publiczny Zaklad Opieki Zdrowotnej ( Site 0708)
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Kielce, Swietokrzyskie, Poland
National Cancer Centre Singapore ( Site 1501)
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Singapore, Central Singapore, Singapore
National Cheng Kung University Hospital ( Site 1201)
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Tainan, Taiwan
Rambam Health Care Campus-Gyneco-oncology unit ( Site 0602)
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Haifa, Israel
Fondazione Policlinico Universitario Agostino Gemelli-Ginecologia Oncologica ( Site 0502)
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Roma, Lazio, Italy
National University Hospital ( Site 1502)
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Singapore, South West, Singapore
Istituto Nazionale Tumori IRCCS Fondazione Pascale-S.C. Oncologia Sperimentale Uro-Genitale ( Site 0
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Napoli, Campania, Italy
Antwerp University Hospital-Oncology ( Site 1301)
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Edegem, Antwerpen, Belgium
Fondazione IRCCS Istituto Nazionale dei Tumori-Struttura Complessa Chirurgia Ginecologica ( Site 050
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Milan, Lombardia, Italy
National Taiwan University Hospital-Internal Medicine ( Site 1200)
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Taipei, Taiwan
James Lind Centro de Investigación del Cáncer ( Site 0903)
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Temuco, Araucania, Chile
Pontificia Universidad Catolica de Chile-Centro del Cáncer ( Site 0900)
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Santiago, Region M. De Santiago, Chile
Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - P-Klinika Ginekologii Onkologicznej ( Sit
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Warszawa, Mazowieckie, Poland
Uniwersytecki Szpital Kliniczny w Poznaniu-Oddzial Ginekologii Onkologicznej ( Site 0709)
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Poznan, Wielkopolskie, Poland
Rutgers Cancer Institute of New Jersey ( Site 0114)
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New Brunswick, New Jersey, United States
Mazowiecki Szpital Wojewódzki w Siedlcach-Siedleckie Centrum Onkologii ( Site 0701)
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Siedlce, Mazowieckie, Poland
Instituto Catalan de Oncologia - Hospital Duran i Reynals-Medical Oncology ( Site 1103)
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Hospitalet, Barcelona, Spain
Severance Hospital, Yonsei University Health System-Gynecologic cancer center ( Site 0800)
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Seoul, Korea, Republic of
Mayo Clinic in Florida ( Site 0101)
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Jacksonville, Florida, United States
Miami Cancer Institute at Baptist Health, Inc. ( Site 0110)
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Miami, Florida, United States
Northwestern Memorial Hospital ( Site 0104)
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Chicago, Illinois, United States
Washington University ( Site 0113)
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Saint Louis, Missouri, United States
Roswell Park Cancer Institute ( Site 0106)
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Buffalo, New York, United States
Perlmutter Cancer Center at NYU Langone Hospital - Long Island ( Site 0116)
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Mineola, New York, United States
Laura and Isaac Perlmutter Cancer Center at NYU Langone ( Site 0107)
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New York, New York, United States
Memorial Sloan Kettering Cancer Center ( Site 0102)
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New York, New York, United States
Fred Hutchinson Cancer Center ( Site 0100)
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Seattle, Washington, United States
Sanford Cancer Center-Gynecologic Oncology ( Site 0115)
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Sioux Falls, South Dakota, United States
AZ Maria Middelares-IKG ( Site 1302)
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Gent, Oost-Vlaanderen, Belgium
UZ Leuven ( Site 1300)
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Leuven, Vlaams-Brabant, Belgium
Centre Hospitalier de l'Université de Montréal ( Site 0300)
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Montréal, Quebec, Canada
FALP ( Site 0905)
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Santiago, Region M. De Santiago, Chile
McGill University Health Centre ( Site 0301)
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Montréal, Quebec, Canada
ONCOCENTRO APYS-ACEREY ( Site 0904)
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Viña del Mar, Valparaiso, Chile
Sheba Medical Center-ONCOLOGY ( Site 0600)
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Ramat Gan, Israel
Seoul National University Hospital ( Site 0801)
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Seoul, Korea, Republic of
Uniwersyteckie Centrum Kliniczne-Klinika Ginekologii, Ginekologii Onkologicznej i Endokrynologii Gi
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Gdańsk, Pomorskie, Poland
Taichung Veterans General Hospital-GYNECOLOGY ( Site 1202)
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Taichung, Taiwan
Mackay Memorial Hospital ( Site 1204)
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Taipei, Taiwan