Study of Chemotherapy With Pembrolizumab (MK-3475) Followed by Maintenance With Olaparib (MK-7339) for the First-Line Treatment of Women With BRCA Non-mutated Advanced Epithelial Ovarian Cancer (EOC) (MK-7339-001/KEYLYNK-001/ENGOT-ov43/GOG-3036)

Official Title

A Randomized Phase 3, Double-Blind Study of Chemotherapy With or Without Pembrolizumab Followed by Maintenance With Olaparib or Placebo for the First-Line Treatment of BRCA Non-mutated Advanced Epithelial Ovarian Cancer (EOC) (KEYLYNK-001 / ENGOT-ov43 / GOG-3036)

Summary:

The purpose of this study is to assess the efficacy and safety of treatment with carboplatin/paclitaxel* PLUS pembrolizumab (MK-3475) and maintenance olaparib (MK-7339) in women with epithelial ovarian cancer (EOC), fallopian tube cancer, or primary peritoneal cancer. The primary study hypotheses are that the combination of pembrolizumab plus carboplatin/paclitaxel* followed by continued pembrolizumab and maintenance olaparib is superior to carboplatin/paclitaxel alone with respect to Progression Free Survival (PFS) per Response Evaluation Criteria in Solid Tumours Version 1.1 (RECIST 1.1) in participants with programmed death-ligand 1 (PD-L1)-positive tumours (Combined Positive Score [CPS]≥10) and in all participants, and that the combination of pembrolizumab plus carboplatin/paclitaxel followed by continued pembrolizumab is superior to carboplatin/paclitaxel alone with respect to PFS per RECIST 1.1 in participants with PD-L1-positive tumours (CPS≥10) and in all participants.

Trial Description

Primary Outcome:

• Progression-Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumours Version 1.1 (RECIST 1.1) as Assessed by the Investigator in Participants with Programmed Death-Ligand 1 (PD-L1)-Positive Tumours (Combined Positive Score [CPS]≥10) Tumours
• PFS Per RECIST 1.1 as Assessed by the Investigator in All Participants

Secondary Outcome:

• Overall Survival (OS) in All Participants
• PFS Per RECIST 1.1 as Assessed by Blinded Independent Central Review (BICR) in Participants with PD-L1-Positive Tumours (CPS≥10) Tumours
• PFS Per RECIST 1.1 as Assessed by BICR in All Participants
• PFS After Next-line Treatment (PFS2) Following Discontinuation of Study Treatment as Assessed by the Investigator in Participants with PD-L1-Positive Tumours (CPS≥10) Tumours
• PFS2 Following Discontinuation of Study Treatment as Assessed by the Investigator in All Participants
• Number of Participants Who Experience an Adverse Event (AE)
• Number of Participants Who Discontinue Study Treatment Due to an AE
• Change from Baseline in Global Health Status/Quality of Life (GHS/QoL) Score Using Questions from the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30)
• Change from Baseline in Abdominal and Gastrointestinal (Abdominal/GI) Symptoms Score Using the EORTC Quality of Life Questionnaire-Ovarian Cancer (QLQ-OV28) Abdominal/GI Symptom Scale
• Time to First Subsequent Anti-cancer Treatment (TFST)
• Time to Second Subsequent Anti-cancer Treatment (TSST)
• Time to Discontinuation of Study Treatment or Death (TDT)
• Pathological Complete Response (pCR) Rate
• Time Without Symptom of Disease Progression or Toxicity of Treatment (TWiST)

Following a lead-in period during which all participants receive a single 3-week cycle of carboplatin/paclitaxel*, participants will be randomly assigned in to one of three treatment arms:

• Pembrolizumab + Olaparib,

• Pembrolizumab + Placebo for Olaparib

• Placebo for Pembrolizumab + Placebo for Olaparib

• At Investigator's discretion and prior to participant randomization, one of the following carboplatin/paclitaxel regimens is to be selected: 1. up to 5 cycles of carboplatin Area Under the Curve (AUC)5 or AUC6 AND paclitaxel 175 mg/m^2 on Day 1 of each 3-week cycle 2. up to 5 cycles of carboplatin AUC5 or AUC6 on Day 1 of each 3-week cycle AND paclitaxel 80 mg/m^2 on Days 1, 8 and 15 of each 3-week cycle; or 3. up to 5 cycles of carboplatin AUC2 or AUC2.7 AND paclitaxel 60 mg/m^2 on Days 1, 8 and 15 of each 3-week cycle. Docetaxel may be considered for participants who experience either a severe hypersensitivity reaction to paclitaxel or an AE requiring discontinuation of paclitaxel only after consultation with the Sponsor. The recommended dose as determined by the Scottish Gynaecological Cancer Trials Group is Docetaxel 75 mg/m^2 Q3W plus carboplatin AUC 5 Q3W.

View this trial on ClinicalTrials.gov