Efficacy and Safety of Pembrolizumab (MK-3475) in Combination With Bacillus Calmette-Guerin (BCG) in High-Risk Non-Muscle Invasive Bladder Cancer (HR NMIBC) (MK-3475-676/KEYNOTE-676)

Official Title

A Phase 3, Randomized, Comparator-controlled Clinical Trial to Study the Efficacy and Safety of Pembrolizumab (MK-3475) in Combination With Bacillus Calmette-Guerin (BCG) in Participants With High-risk Non-muscle Invasive Bladder Cancer (HR NMIBC) That is Either Persistent or Recurrent Following BCG Induction or That is Naïve to BCG Treatment (KEYNOTE-676)

Summary:

This study is designed to assess the antitumour efficacy and safety of pembrolizumab in combination with BCG, compared to BCG monotherapy, in participants with HR NMIBC that is either persistent or recurrent following adequate BCG induction (Cohort A), or that is naïve to BCG treatment (Cohort B). The primary hypothesis for Cohort A is that the combination of pembrolizumab plus BCG has a superior complete response rate (CRR) as assessed by central pathology review compared to BCG in participants with carcinoma in situ (CIS). The primary hypothesis for Cohort B is that the combination of pembrolizumab plus BCG (either reduced maintenance or full maintenance) has a superior Event Free Survival (EFS) compared to BCG.

Trial Description

Primary Outcome:

• Complete Response Rate (CRR) by Blinded Independent Central Review (BICR) (Cohort A)
• Event-Free Survival (EFS) (Cohort B)

• EFS (Cohort A)
• Recurrence-Free Survival (RFS) (Cohorts A and B)
• Overall Survival (OS) (Cohorts A and B)
• Disease Specific Survival (DSS) (Cohorts A and B)
• Time to Cystectomy (Cohorts A and B)
• 12-Month EFS Rate (Cohort A)
• Duration of Response (DOR) (Cohorts A and B)
• 12-Month DOR Rate (Cohorts A and B)
• Percentage of Participants Experiencing Adverse Events (AEs) (Cohorts A and B)
• Percentage of Participants Discontinuing Study Drug Due to AEs (Cohorts A and B)
• Change from Baseline in the European Organization for Research and Treatment of Cancer (EORTC)-Quality of Life Questionnaire-Core 30 (QLQ-C30) Global Health Status/Quality of Life (Items 29 and 30) Combined Score (Cohorts A and B)
• Change from Baseline in EORTC-QLQ-C30 Physical Functioning (Items 1-5) Combined Score (Cohorts A and B)
• Change from Baseline in EORTC-QLQ-Non-muscle Invasive Bladder Cancer Module 24 (NMIBC24) Total Score (Cohorts A and B)
• Change from Baseline in European Quality of Life (EuroQoL)-5 Dimensions, 5-level Questionnaire (EQ-5D-5L) Visual Analogue Score (VAS) (Cohorts A and B)
• Time to Deterioration (TTD) in the EORTC-QLQ-C30 Global Health Status/Quality of Life (Items 29 and 30) Combined Score (Cohorts A and B)
• TTD in the EQ-5D-5L VAS (Cohorts A and B)
• CRR by BICR (Cohort B)
• 24-Month EFS Rate (Cohort B)

View this trial on ClinicalTrials.gov