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Brief Title: 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)

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)

INTRODUCTION

  • Org Study ID: 3475-676
  • Secondary ID: MK-3475-676, 194713, 2018-001967-22
  • NTC ID: NCT03711032
  • Sponsor: Merck Sharp & Dohme LLC
Merck Oncology Clinical Trials Information

BRIEF SUMMARY

This study is designed to assess the antitumor 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.

  • Overall Status
    Recruiting
  • Start Date
    December 24, 2018
  • Phase
    Phase 3
  • Study Type
    Interventional

PRIMARY OUTCOMES

Primary Outcome 1 - Measure: Complete Response Rate (CRR) by Blinded Independent Central Review (BICR) (Cohort A)

Primary Outcome 1 - Timeframe: Up to ~3.5 years

Primary Outcome 2 - Measure: Event-Free Survival (EFS) (Cohort B)

Primary Outcome 2 - Timeframe: Up to ~5 years

CONDITION

  • High-risk Non-muscle Invasive Bladder Cancer

ELIGIBILITY

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

- 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 concurrent extra-vesical (i.e, urethra, ureter, renal pelvis) non-muscle invasive urothelial carcinoma or a history of extra-vesical non-muscle invasive UC

- Has received prior therapy with anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor

- Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks of start of study treatment

- Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks of start of study treatment

- Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days of start of study treatment

- Has a known additional malignancy that is progressing or requires active treatment within the past 3 years

- Has an active autoimmune disease that has required systemic treatment in past 2 years

- Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease

- 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

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

OFFICIAL INFORMATION

Name: Medical Director

Role: Study Director

Affiliation: Merck Sharp & Dohme LLC

Overall Contact

Name: Medical Director

Phone: 1-888-577-8839

Email: Trialsites@merck.com

LOCATION

Facility Status Contact