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

Merck Sharp & Dohme (MSD)

Status and phase: Completed; Phase 2

Conditions: High-grade Serous Ovarian Carcinoma; Ovarian Carcinoma

Treatments: Biological: Pembrolizumab; Drug: Carboplatin; Drug: Paclitaxel; Biological: MK-4830; Drug: Docetaxel; Biological: Avastin

Study type: Interventional

Funder types: Industry

Identifiers

NCT05446870

2021-005458-27 (EudraCT Number)

2023-505005-16 (Registry Identifier)

4830-002

MK-4830-002 (Other Identifier)

Details and patient eligibility

About

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.

Enrollment: 160 patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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160 participants in 2 patient groups

Pembrolizumab + Standard of Care (SOC) + MK-4830

Experimental group

Description:

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.

Treatment:

Drug: Docetaxel

Biological: Avastin

Biological: MK-4830

Drug: Paclitaxel

Drug: Carboplatin

Biological: Pembrolizumab

Pembrolizumab + SOC

Active Comparator group

Description:

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.

Treatment:

Drug: Docetaxel

Biological: Avastin

Drug: Paclitaxel

Drug: Carboplatin

Biological: Pembrolizumab