988TiPKEYNOTE-866: Phase III study of perioperative pembrolizumab (pembro) or placebo (pbo) in combination with neoadjuvant chemotherapy in cisplatin (cis)-eligible patients (pts) with muscle-invasive bladder cancer (MIBC)

Abstract Background MIBC is associated with a high rate of recurrence and poor overall prognosis despite aggressive local and systemic therapy. With standard therapy of neoadjuvant cis-based chemotherapy (CT), only a modest 5-year survival benefit is seen after radical cystectomy (RC). Recently, neoadjuvant CT and pembro showed efficacy in cis-eligible pts with MIBC (NCT02365766). Trial design KEYNOTE-866 (NCT03924856) is a randomized, multicenter, global, phase 3 trial to assess efficacy and safety of perioperative pembro + CT vs perioperative pbo + CT for pts with MIBC. Adult pts (≥18 y) with histologically confirmed MIBC (T2-T4aN0M0) with predominant (≥50%) urothelial histology, confirmed by blinded independent central review, are eligible. Pts must be previously untreated, be cis-eligible, have ECOG PS 0/1, and have tumor tissue for histology and PD-L1 analysis. About 790 pts will be randomly assigned 1:1 to receive 4 cycles of neoadjuvant pembro + CT followed by 13 cycles of adjuvant pembro after RC + pelvic lymph node dissection (PLND) or 4 cycles of neoadjuvant pbo + CT followed by 13 cycles of adjuvant pbo after RC + PLND. Neoadjuvant/adjuvant pembro 200 mg will be administered every 3 weeks (Q3W); neoadjuvant CT consists of 4 cycles of gemcitabine 1000 mg/m2 + cis 70 mg/m2 Q3W. Pts will be stratified by PD-L1 status (combined positive score [CPS] ≥10 vs  Clinical trial identification NCT03924856, April 23, 2019. Editorial acknowledgement Matthew Grzywacz, PhD, of the ApotheCom pembrolizumab team (Yardley, PA, USA), funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. Legal entity responsible for the study Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. Funding Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. Disclosure A.O. Siefker-Radtke: Advisory / Consultancy, Travel / Accommodation / Expenses: Merck Sharp & Dohme; Advisory / Consultancy, Travel / Accommodation / Expenses: Janssen; Advisory / Consultancy, Travel / Accommodation / Expenses: Nektar Therapeutics; Advisory / Consultancy, Travel / Accommodation / Expenses: Seattle Genetics; Advisory / Consultancy: Bavarian Nordic. G. Steinberg: Honoraria (self), Advisory / Consultancy: Merck; Honoraria (self), Advisory / Consultancy: BMS; Honoraria (self), Advisory / Consultancy, Shareholder / Stockholder / Stock options: Urogen; Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy: Janssen; Honoraria (self), Advisory / Consultancy: Boston Scientific; Honoraria (self), Advisory / Consultancy: Cold Genesys; Honoraria (self), Advisory / Consultancy: PhotoCure; Honoraria (self), Advisory / Consultancy: Aduro; Honoraria (self), Advisory / Consultancy: Asieris; Honoraria (self), Advisory / Consultancy: Ciclomed; Honoraria (self), Advisory / Consultancy: Pfizer; Honoraria (self), Advisory / Consultancy: Genentech; Honoraria (self), Advisory / Consultancy: MDxHealth; Honoraria (self), Advisory / Consultancy: Ferring; Honoraria (self), Advisory / Consultancy: Fidia; Shareholder / Stockholder / Stock options: Epivax Oncology. J. Bedke: Advisory / Consultancy: BMS, Roche, MSD, Pfizer; Speaker Bureau / Expert testimony, Research grant / Funding (institution): BMS, Roche, MSD. J. Martin: Shareholder / Stockholder / Stock options, Full / Part-time employment: Merck & Co., Inc. R. Kataria: Shareholder / Stockholder / Stock options, Full / Part-time employment: Merck & Co., Inc. T.L. Frenkl: Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options, Full / Part-time employment: MSD. C.J. Hoimes: Advisory / Consultancy: Seattle Genetics, Merck; Speaker Bureau / Expert testimony: Bristol-Myers Squibb, Genentech. All other authors have declared no conflicts of interest.