PURE-01 (NCT02736266) is an open-label, single-arm, phase 2 study aiming 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 patients. Patients 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 multipara metric magnetic resonance imaging (mpMRI) are done during screening and before RC. Radiologically non-responders to pembro (per investigator decision) are given 3 additional courses of dose-dense MVAC chemotherapy. After RC, patients 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 patients enrolled who receive at least 1 cycle of study drug will be included in the intention to treat (ITT) analysis. The H1 hypothesis is pT0 ≥20% and H0 hypothesis is pT0≤10%.
In a 2-stage design, 90 patients overall will be accrued (80% power and a 2-sided test of significance at the 10% level). Since Jan 30th 2018, 40/90 patients have been recruited so far. 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
Presented by: Andrea Necchi, MD Milano, Italy
Co Authors: Alberto Briganti, Daniele Raggi, Patrizia Giannatempo, Luigi Mariani, Antonella Messina, Andrea Anichini, Giuseppina Calareso, Flavio Crippa, Mario Catanzaro, Nicola Fossati, Giorgio Gandaglia, Andrea Salonia, Roberto Salvioni, Francesco Montorsi; Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy; Vita-Salute San Raffaele University, Urological Research Institute, IRCCS San Raffaele Hospital, Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy; IRCCS Ospedale San Raffaele, Milan, Italy; Vita-Salute San Raffaele University, Urological Research Institute, IRCCS San Raffaele Hospital, Milano, Italy; Vita-Salute San Raffaele University, IRCCS San Raffaele Scientific Institute, Milan, Italy
Written by: Hanan Goldberg, MD, Urologic Oncology Fellow (SUO), University of Toronto, Princess Margaret Cancer Centre @GoldbergHanan at the 2018 American Society of Clinical Oncology Genitourinary (ASCO GU) Cancers Symposium, February 8-10, 2018 - San Francisco, CA
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