Bacillus Calmette-Guerin (BCG) with or without pembrolizumab (pembro) for high-risk (HR) nonmuscle invasive bladder cancer (NMIBC) that is persistent or recurrent following BCG induction: Phase III KEYNOTE-676 study.

Abstract

TPS4591 Background: Intravesical instillation of BCG is standard of care for patients (pts) with HR NMIBC. However, many pts have persistent/recurrent HR NMIBC after BCG induction and are at increased risk for progression to muscle-invasive disease. Interim data from the phase 2 KEYNOTE-057 study has shown that the PD-1 inhibitor pembro had promising efficacy in HR NMIBC as monotherapy. KEYNOTE-676 (NCT03711032) is a randomized, comparator-controlled, phase 3 trial to evaluate efficacy and safety of pembro plus BCG in pts with persistent/recurrent HR NMIBC after BCG induction therapy. Methods: Pts are randomly assigned 1:1 to continue BCG therapy alone or receive BCG plus pembro 200 mg every 3 weeks. Treatment is stratified by carcinoma in situ (CIS) histology (presence/absence), PD-L1 combined positive score (≥10/˂10), and timing of NMIBC persistence/recurrence (0 to ≤6, ˃6 to ≤12, or ˃12 to ≤24 mo). Pts are eligible if they are ≥18 years of age with histologically confirmed persistent/recurrent HR NMIBC of the bladder after adequate BCG induction therapy, have undergone cystoscopy/transurethral resection of bladder tumor within 12 weeks before randomization, have no concurrent extravesical disease, and have an ECOG PS score of 0-2. Responses are assessed by cystoscopy and blinded independent central review of urine cytology and biopsy (as applicable) every 12 weeks for years 1-2 and every 24 weeks for years 3-5 and by computed tomography urography every 18 months through year 5. Treatment will continue with pembro for up to 2 years and BCG for 3 years or until confirmed HR NMIBC persistence, recurrence, or disease progression, unacceptable toxicity, or pt/physician decision to withdraw. Primary end point is complete response rate in pts with CIS. Secondary end points are event-free survival (EFS), recurrence-free survival, overall survival, disease-specific survival, time to cystectomy, 12-month EFS rate in all pts, duration of response (DOR), 12-month DOR rate in pts with CR and safety and tolerability. Recruitment began in November 2018 and will continue until ~550 pts are enrolled. Clinical trial information: NCT03711032.