Pembrolizumab With Chemotherapy and MK-4830 for Treating Participants With Ovarian Cancer (MK-4830-002)
- Conditions
- High-grade Serous Ovarian CarcinomaOvarian Carcinoma
- Interventions
- 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 deoxyribonucleic acid (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
- 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.
- 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 ovarian cancer (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 + Standard of Care (SOC) + MK-4830 Pembrolizumab 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. Pembrolizumab + Standard of Care (SOC) + MK-4830 Paclitaxel 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. Pembrolizumab + Standard of Care (SOC) + MK-4830 Carboplatin 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. Pembrolizumab + Standard of Care (SOC) + MK-4830 Avastin 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. Pembrolizumab + Standard of Care (SOC) + MK-4830 MK-4830 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. Pembrolizumab + Standard of Care (SOC) + MK-4830 Docetaxel 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. Pembrolizumab + SOC Pembrolizumab 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. Pembrolizumab + SOC Paclitaxel 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. Pembrolizumab + SOC Carboplatin 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. Pembrolizumab + SOC Avastin 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. Pembrolizumab + SOC Docetaxel 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.
- 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 Participants With Surgery and Pathological Complete Response (pCR): Change From Baseline in ctDNA Baseline and Week 12 Blood samples were collected to determine levels of ctDNA. pCR was defined as all surgical specimens collected during the interval debulking surgery microscopically negative for residual tumor. Per protocol, change from baseline in ctDNA in participants with surgery and pCR was reported.
Association of Change From Baseline in ctDNA With pCR Baseline and Week 12 Blood samples were collected to determine levels of ctDNA. pCR was defined as all surgical specimens collected during the interval debulking surgery microscopically negative for residual tumor. pCR rate was defined as percentage of participants with pCR. Per protocol, the association of change from baseline in ctDNA with pCR in participants with surgery and pCR was reported.
Participants With Surgery and Chemotherapy Response Score (CRS): Change From Baseline in ctDNA Baseline and Week 12 Blood samples were collected to determine levels of ctDNA. CRS is a 3-tiered scoring system (CRS1-3) based on the pathological analysis of surgically removed omental masses. CRS was defined as CRS1 (minimal or no tumor response, mainly viable tumor), CRS2 (appreciable tumor response amidst viable tumor that is readily identifiable and regularly distributed), and 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); higher values indicate greater response. Per protocol, change from baseline in ctDNA in participants with surgery and CRS was reported.
Association of Change From Baseline in ctDNA With CRS3 Baseline and Week 12 Blood samples were collected to determine levels of ctDNA. CRS is a 3-tiered scoring system (CRS1-3) based on the pathological analysis of surgically removed omental masses. CRS was defined as CRS1 (minimal or no tumor response, mainly viable tumor), CRS2 (appreciable tumor response amidst viable tumor that is readily identifiable and regularly distributed), and 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); higher values indicate greater response. CRS3 rate was defined as percentage of participants with CRS3. Per protocol, the association of change from baseline in ctDNA with CRS3 in participants with surgery and CRS was reported.
pCR Rate Up to approximately 12 weeks pCR rate was defined as the percentage of participants with all surgical specimens collected during the interval debulking surgery that were microscopically negative for residual tumor. The pCR rate as assessed by local pathologist was reported.
CRS3 Rate Up to approximately 12 weeks CRS is a 3-tiered scoring system (CRS1-3) based on the pathological analysis of surgically removed omental masses. CRS was defined as CRS1 (minimal or no tumor response, mainly viable tumor), CRS2 (appreciable tumor response amidst viable tumor that is readily identifiable and regularly distributed), and 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); higher values indicate greater response. CRS3 rate was defined as percentage of participants with CRS3. Per protocol, CRS3 rate as assessed by local pathologist was reported.
Number of Participants Who Experienced an Adverse Event (AE) Up to approximately 26 months An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE could have been any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated). The number of participants who experienced one or more AEs was reported.
Number of Participants Who Discontinued Study Intervention Due to an AE Up to approximately 28 weeks An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE could have been any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated). The number of participants who discontinued study intervention due to an AE was reported.
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Trial Locations
- Locations (45)
University of Colorado Anschutz Medical Campus-Cancer Clinical Trials Office ( Site 0108)
🇺🇸Aurora, Colorado, United States
Mayo Clinic in Florida ( Site 0101)
🇺🇸Jacksonville, Florida, United States
Miami Cancer Institute at Baptist Health, Inc. ( Site 0110)
🇺🇸Miami, Florida, United States
Northwestern Memorial Hospital ( Site 0104)
🇺🇸Chicago, Illinois, United States
Washington University ( Site 0113)
🇺🇸St Louis, Missouri, United States
Rutgers Cancer Institute of New Jersey ( Site 0114)
🇺🇸New Brunswick, New Jersey, United States
Roswell Park Cancer Institute ( Site 0106)
🇺🇸Buffalo, New York, United States
Perlmutter Cancer Center at NYU Langone Hospital - Long Island ( Site 0116)
🇺🇸Mineola, New York, United States
Laura and Isaac Perlmutter Cancer Center at NYU Langone ( Site 0107)
🇺🇸New York, New York, United States
Memorial Sloan Kettering Cancer Center ( Site 0102)
🇺🇸New York, New York, United States
Scroll for more (35 remaining)University of Colorado Anschutz Medical Campus-Cancer Clinical Trials Office ( Site 0108)🇺🇸Aurora, Colorado, United States