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Clinical Trials/2022-501817-29-00
2022-501817-29-00
Active, not recruiting
Phase 3

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)

Merck Sharp & Dohme LLC57 sites in 13 countries559 target enrollmentStarted: April 27, 2023Last updated:
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Overview

Phase
Phase 3
Status
Active, not recruiting
Enrollment
559
Locations
57
Primary Endpoint
Complete Response Rate (CRR) by Blinded Independent Central Review (BICR) (Cohort A)
OverviewStudy DesignEligibility CriteriaOutcomesInvestigatorsSitesRecords & IdentifiersSimilar Trials

Overview

Brief Summary

  1. Cohort A: To compare the CRR for the combination of pembrolizumab + BCG versus BCG alone in participants with CIS
  2. Cohort B: To compare the EFS between participants who receive pembrolizumab + BCG (reduced maintenance) versus BCG alone
  3. Cohort B: To compare the EFS between participants who receive pembrolizumab+ BCG (full maintenance) versus BCG alone

Study Design

Allocation
Randomized
Primary Purpose
Unblinded open-label treatment
Masking
None

Eligibility Criteria

Ages
18 years to 65+ years (18-64 Years, 65+ Years)
Accepts Healthy Volunteers
Yes

Inclusion Criteria

  • •Have locally and blinded independent central review (BICR)-confirmed histological diagnosis of high-risk non-muscle invasive (T1, high grade Ta and/or CIS) UC of the bladder
  • •Has undergone cystoscopy/ transurethral resection of bladder tumor (TURBT) to remove all resectable disease
  • •Has provided tissue for biomarker analysis
  • •Has Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2
  • •Has adequate organ function
  • •During the treatment period and for ≥7 days after the last dose of BCG, male participants are EITHER abstinent from heterosexual intercourse as their preferred and usual lifestyle and agree to remain abstinent, OR, must agree to use contraception unless confirmed to be azoospermic
  • •Female participants who are not pregnant, not breastfeeding, and either not a woman of child bearing potential (WOCBP); or are a WOCBP who agrees to use a contraception method that is highly effective or remains abstinent from heterosexual intercourse during the treatment period and for ≥7 days after the last dose of BCG or 120 days after the last dose of pembrolizumab, whichever comes last
  • •BCG Post-induction Cohort (Cohort A) Only: Has been treated with one adequate course of BCG induction therapy for the treatment of HR NMIBC
  • •BCG Post-induction Cohort (Cohort A) Only: Following adequate BCG induction therapy, must have persistent or recurrent HR NMIBC

Exclusion Criteria

  • •Has a history of or concurrent locally advanced (i.e., T2, T3, T4) or metastatic UC
  • •Has one or more of the following contraindications to BCG: prior BCG sepsis or systemic infection, total bladder incontinence, or an adverse experience to a previous BCG instillation that resulted in treatment discontinuation and precludes retreating with BCG
  • •Has an active infection or diagnosis requiring systemic antimicrobial 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 current active tuberculosis
  • •Has had an allogenic-tissue/solid organ transplant
  • •Has any contraindication(s) to IV contrast or is otherwise unable to have screening imaging with IV contrast performed
  • •BCG Post-induction Cohort (Cohort A) Only: Has persistent T1 disease following an induction course of BCG
  • •BCG Naïve Cohort (Cohort B) Only: Has received any prior treatment with BCG for their NMIBC within the past 2 years prior to study entry

Outcomes

Primary Outcomes

Complete Response Rate (CRR) by Blinded Independent Central Review (BICR) (Cohort A)

Complete Response Rate (CRR) by Blinded Independent Central Review (BICR) (Cohort A)

Event-Free Survival (EFS) (Cohort B)

Event-Free Survival (EFS) (Cohort B)

Secondary Outcomes

  • 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)

Investigators

Sponsor Class
Pharmaceutical company
Responsible Party
Principal Investigator
Principal Investigator

Hema Dave

Scientific

Merck Sharp & Dohme LLC

Study Sites (57)

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