Phase III study of perioperative pembrolizumab (pembro) plus neoadjuvant chemotherapy (chemo) versus placebo plus neoadjuvant chemo in cisplatin-eligible patients (pts) with muscle-invasive bladder cancer (MIBC): KEYNOTE-866.

Abstract

TPS599 Background: MIBC prognosis is poor, despite standard neoadjuvant cisplatin-based chemo. PD-1/PD-L1 pathway inhibition is an effective first-line option for cisplatin-ineligible pts and a second-line option for platinum-based chemo pretreated pts. Neoadjuvant chemo + pembro, a PD-1 inhibitor, recently showed encouraging pathologic complete response rates, in cisplatin-eligible patients with MIBC (NCT02365766), warranting further investigation. Methods: KEYNOTE-866 (NCT03924856) is a randomized phase 3 study to assess efficacy and safety of chemo+perioperative pembro versus chemo+perioperative placebo for pts with MIBC. An estimated 790 patients will be randomly assigned 1:1 to neoadjuvant pembro+chemo (4 cycles) followed by adjuvant pembro after radical cystectomy+pelvic lymph node dissection (RC+PLND, 13 cycles) or neoadjuvant placebo+chemo (4 cycles) followed by adjuvant placebo after RC+PLND (13 cycles). Pts will receive neoadjuvant and adjuvant pembro 200 mg IV Q3W; neoadjuvant chemo will be gemcitabine 1000 mg/m2+cisplatin 70 mg/m2 IV Q3W. Pts will be stratified by tumor PD-L1 status (combined positive score [CPS] ≥10 vs CPS <10), disease stage (T2 vs T3/4), and region of treatment (Unites States vs Europe vs most of world). Adults (≥18 y) with histologically confirmed MIBC (T2-T4aN0M0) who are cisplatin-eligible, are clinically nonmetastatic (N0M0), and have an ECOG PS 0 or 1 will be enrolled. Pts are required to provide tumor tissue for histology and PD-L1 analysis. Pts will not be permitted to have previously received systemic antineoplastic treatment for MIBC or radiotherapy to the bladder. Imaging by CT/MRI will be performed Q12W for up to 96 wk after cystectomy, at discontinuation, and during follow-up starting at 3 y (Q24W). Primary end points are pathologic complete response and event-free survival in all pts and pts with PD-L1 CPS ≥10. Secondary end points are OS, disease-free survival, and pathologic downstaging rate in all pts and pts with PD-L1 CPS ≥10, and safety. Accrual began June 13, 2019. Clinical trial information: NCT03924856.