Phase III study of perioperative pembrolizumab (pembro) plus cystectomy versus cystectomy alone in cisplatin-ineligible patients (pts) with muscle-invasive bladder cancer (MIBC): KEYNOTE-905.

Abstract

TPS593 Background: Pts with MIBC ineligible for neoadjuvant cisplatin-based chemotherapy who only receive the standard radical cystectomy+pelvic lymph node dissection (RC+PLND) have a high rate of recurrence and poor prognosis. PD-1/PD-L1 inhibition is an effective first-line option for cisplatin-ineligible pts. Neoadjuvant single-agent pembro, a PD-1 inhibitor, has shown activity in pts with MIBC, with a pathologic complete response (pCR) rate of 42% for all pts and 54% for PD-L1+ pts (PURE-01; NCT02736266). Methods: KEYNOTE-905 (NCT03924895) is a randomized phase 3 trial of preoperative pembro plus RC+PLND versus RC+PLND alone in cisplatin-ineligible pts with MIBC. An estimated 610 pts will be enrolled and randomly assigned 1:1 to either neoadjuvant pembro (3 cycles) followed by RC+PLND and adjuvant pembro (14 cycles) or RC+PLND alone and observation. Pembro 200 mg will be administered IV every 3 weeks. Pts in the RC+PLND group will proceed directly to RC+PLND within 8 weeks from randomization. Pts will be stratified by clinical T stage (T2 vs T3 or T4), PD-L1 expression (combined positive score [CPS] ≥10 vs <10), and geographic region (United States vs Europe vs most of world). Adults (≥18 years) ineligible to receive cisplatin with histologically confirmed MIBC (T2-T4aN0M0), clinically nonmetastatic disease (N0M0), and an ECOG PS score of 0-2 are eligible. Previous systemic anticancer therapies for MIBC are not permitted. CT/MRI will be performed before and after cystectomy. Pts disease free after imaging for cystectomy will continue to undergo serial imaging until disease progression or discontinuation from the study; all imaging will be assessed by blinded independent central review. Coprimary end points are pCR (based on central pathology review) and event-free-survival in all pts and in pts with tumor PD-L1 CPS ≥10. Secondary end points are OS, disease-free survival, and pathologic downstaging in all pts and in pts with tumor PD-L1 CPS ≥10, and safety. Exploratory end points include patient-reported outcomes and biomarkers. Accrual began July 24, 2019. Clinical trial information: NCT03924895.