894TiPPROSTRATEGY: A Spanish Genitourinary Oncology Group (SOGUG) multi-arm multistage (MAMS) phase III trial of immunotherapy strategies in high-volume metastatic hormone-sensitive prostate cancer

Abstract Background The addition of docetaxel (Dx) to androgen deprivation therapy (ADT), as first-line in patients (pt) with high-volume metastatic hormone-sensitive prostate cancer (hvHSPC) has demonstrated to increase time to biochemical, radiographic and clinical progression (bPFS, rPFS, cPFS), as well as overall survival (OS) in two different trials. We hypothesized that early addition of immunotherapy (I/O) or other new drugs to ADT+Dx could improve outcomes. A MAMS has been designed to optimize resources and recruitment, by concurrently comparing different new strategies, and selecting the most effective(s) for a final phase III trial. Trial design PROSTRATEGY is a randomized MAMS trial in pt with hvHSPC, comparing ADT+Dx (control arm: ADT + 6 cycles of Dx 75 mg/m2 + GCSF), to ADT+DX+Nivo (ADT+Dx followed by Nivolumab 3 mg/Kg/2w x 12 mo), or ADT+Ipi+Dx+Nivo (ADT + 2 cycles of Ipilimumab 3 mg/Kg/3w, followed by 3 cycles of Dx + GCSF, 2 cycles of Ipilimumab, 3 cycles of Dx + GCSF, and then Nivolumab 3 mg/Kg/2w x 12 mo). Randomization rate (ADT+Dx/experimental arms) is 2/1. The design allows that additional experimental arms with ADT+DX + other potential active drugs could also be incorporated in the future to the study. According to a priori established criteria based on cPFS, those arms considered not sufficiently effective at any of the 3 planned intermediate stages, will be closed. Those arms that meet the intermediate endpoints will remain in the study, and will be compared to ADT-DX in a seamless phase III trial, with OS (HR = 0.75) as a primary end-point. The pilot phase with the first 120 pt of the first stage of the trial has been started in 30 centres in Spain funded by Bristol-Myers Squibb. The aim is to assess safety of I/O arms, and to estimate and compare outcomes based on RECIST, iRECIST and PCWG3 criteria of efficacy. Collaboration with other cooperative groups is also planned after the pilot phase. Clinical trial identification 2017-004377-13. Legal entity responsible for the study SOGUG: Spanish Oncology Genito-Urinary Group. Funding Bristol-Myers Squibb. Disclosure J.A. Arranz Arija: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Novartis; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: MSD Oncology; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Janssen-Cilag; Honoraria (self), Advisory / Consultancy: EUSA Pharma; Honoraria (self), Advisory