Interim results from PURE-01: A phase 2, open-label study of neoadjuvant pembrolizumab (pembro) before radical cystectomy for muscle-invasive urothelial bladder carcinoma (MIUC).

Abstract

TPS533 Background: MIUC is an aggressive disease and > 40% of patients (pts) will develop recurrence after radical cystectomy (RC). Despite cisplatin-based neoadjuvant chemotherapy yields Level 1 evidence, it is administered in a minority of pts worldwide. Pembro is an EMA and FDA-approved standard therapy for metastatic UC after platinum failure or for cisplatin-ineligible pts. Our hypothesis was that pembro, given neoadjuvantly, could downstage MIUC and reduce recurrence. Methods: PURE-01 (NCT02736266) is an open-label, single-arm, phase 2 study to evaluate the activity, medical and surgical safety, and immune modulatory effects of pembro administered as a short window-of-opportunity course of therapy preceding RC. Eligibility criteria included: T2-T4aN0 stage, and residual disease after transurethral resection of the bladder (TURB, surgical opinion, cystoscopy or radiological presence). The study includes cisplatin eligible- and ineligible pts. Pts receive 3 cycles of pembro 200mg 3 weekly before RC (planned < 3 weeks of the last dose). Computed tomography (CT) scan, FDG-PET/CT scan, and bladder multiparametric magnetic resonance imaging (mpMRI) are done during screening and before RC. Radiologically non responders to pembro (per investigator decision; i.e., study failures) are given 3 additional courses of dose-dense MVAC chemotherapy. After RC, pts are managed according to local guidelines (adjuvant chemotherapy vs observation). Further anti PD-1/PD-L1 therapy will not be given post-operatively. Pathologic complete response (pT0) is the primary endpoint. All pts enrolled who receive at least 1 cycle of study drug will be included in the ITT analysis. The H1 is pT0 ≥20% and H0 pT0≤10%. In a 2-stage design, 90 pts overall will be accrued (80% power and a 2-sided test of significance at the 10% level). A first interim analysis for safety is planned after 18 patients enrolled and treated (by December 1st, 2017). Activity results and early translational findings (immune-cell profiling) will be added, and may be regarded to as first data of preoperative immunotherapy before major surgery. Clinical trial information: NCT02736266.