Preoperative pembrolizumab (pembro) before radical cystectomy (RC) for muscle-invasive urothelial bladder carcinoma (MIUC): Interim clinical and biomarker findings from the phase 2 PURE-01 study.

Abstract

4507Background: MIUC is an aggressive disease and cisplatin-based neoadjuvant chemotherapy is administered in a minority of pts. Pembro is an EMA and FDA-approved therapy for metastatic UC after platinum failure or for cisplatin-ineligible pts. Methods: PURE-01 (NCT02736266) is an open-label, single-arm, phase 2 study. Pts have predominant UC histology and cT≤3bN0 stage. Pts are enrolled regardless of cisplatin eligibility. Disease assessment is made via CT, PET/CT, and multiparametric bladder MRI (mpMRI). Pts receive 3 cycles of pembro 200mg q3w before RC. Pathologic complete response (pT0) in ITT population is the primary endpoint. The H1 is pT0 ≥25% and H0 pT0≤15%. 71 pts will be enrolled, with 43 pts at first stage according to MinMax design. ≥7pT0 are required at first stage. Biomarker analyses include: IHC PD-L1 combined positive score (CPS, Dako 22C3) and genomic sequencing with hybrid-capture based comprehensive genomic profiling. Tumor mutational burden (TMB) is determined on 1.1 Mbp of sequenced...