2944 - PROSTRATEGY: A Spanish Genitourinary Oncology Group (SOGUG) multi-arm multistage (MAMS) phase III trial of immunotherapy strategies in high-volume metastasic hormone-sensitive prostate cancer.

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.

Editorial acknowledgement

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 / Consultancy: Astellas-Pharma; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Bristol-Myers-Squibb; Advisory / Consultancy, Travel / Accommodation / Expenses: Pfizer; Advisory / Consultancy: Bayer; Advisory / Consultancy: Ipsen; Research grant / Funding (institution): Pierre-Fabre. B. P. Valderrama: Honoraria (self), Advisory / Consultancy: Pierre-Fabre; Honoraria (self), Advisory / Consultancy: Astellas Pharma; Honoraria (self): Novartis; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Bristol-Myers-Squibb; Honoraria (self), Advisory / Consultancy: Ipsen; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Honoraria (self), Advisory / Consultancy: Bayer; Advisory / Consultancy: Sanofi-Aventis; Advisory / Consultancy: MSD Oncology; Travel / Accommodation / Expenses: Janssen-Cilag; Travel / Accommodation / Expenses: Pfizer; Advisory / Consultancy: EUSA Pharma. T. Alonso Gordoa: Advisory / Consultancy: Bristol-Myers-Squibb; Advisory / Consultancy: MSD Oncology; Advisory / Consultancy, Research grant / Funding (self): Roche; Advisory / Consultancy, Speaker Bureau / Expert testimony: Astellas Pharma; Advisory / Consultancy, Speaker Bureau / Expert testimony: Ipsen; Advisory / Consultancy, Travel / Accommodation / Expenses: Sanofi-Aventis; Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Pfizer; Speaker Bureau / Expert testimony: Janssen-Cilag; Speaker Bureau / Expert testimony: Novartis. E. Gallardo Diaz: Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Sanofi; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Janssen-Cilag; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Astellas Pharma; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Pfizer; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Bayer; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Ipsen; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Novartis; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Eisai; Advisory / Consultancy: EUSA Pharma; Honoraria (self), Advisory / Consultancy: Bristol-Myers-Squibb; Honoraria (self), Advisory / Consultancy: Rovi; Honoraria (self), Advisory / Consultancy: Daiichi; Honoraria (self), Advisory / Consultancy: Sankyo; Advisory / Consultancy: Techdow; Honoraria (self): Leo Pharma; Honoraria (self): Menarini; Travel / Accommodation / Expenses: Pierre-Fabre; Travel / Accommodation / Expenses: Ferrer; Travel / Accommodation / Expenses: GSK. J.M. Sepulveda Sanchez: Advisory / Consultancy, Travel / Accommodation / Expenses: AbbVie; Advisory / Consultancy, Travel / Accommodation / Expenses: Celgene; Advisory / Consultancy, Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Catalysis; Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Astellas Pharma; Travel / Accommodation / Expenses: Ipsen. J.M. Piulats: Advisory / Consultancy, Research grant / Funding (self), Travel / Accommodation / Expenses: Bristol-Myers-Squibb; Advisory / Consultancy, Research grant / Funding (self): MSD Oncology; Advisory / Consultancy, Research grant / Funding (self): Merck-Serono; Advisory / Consultancy: Novartis; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Janssen-Cilag; Advisory / Consultancy: Clovis; Advisory / Consultancy, Travel / Accommodation / Expenses: Astellas Pharma; Advisory / Consultancy: Roche; Advisory / Consultancy: BeiGene; Advisory / Consultancy: VCN Bioscience; Travel / Accommodation / Expenses: Ipsen; Research grant / Funding (institution): Pfizer; Research grant / Funding (self): Incyte. M.J. Mendez Vidal: Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Janssen-Cilag; Honoraria (self), Advisory / Consultancy: Bayer Healthcare; Honoraria (self), Advisory / Consultancy: Sanofi-Aventis; Honoraria (self), Advisory / Consultancy: Astellas Pharma; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Bristol-Myers-Squibb; Advisory / Consultancy: Novartis; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Pfizer. N. Sala González: Advisory / Consultancy: Pfizer; Advisory / Consultancy: Sanofi. S. Vazquez Estevez: Advisory / Consultancy, Travel / Accommodation / Expenses: Pfizer; Honoraria (self), Advisory / Consultancy: Astellas Pharma; Advisory / Consultancy: Janssen-Cilag; Advisory / Consultancy: MSD Oncology; Honoraria (self), Advisory / Consultancy: Bayer; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Advisory / Consultancy: Bristol-Myers-Squibb; Honoraria (self), Advisory / Consultancy: Boehringer; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: AstraZeneca; Honoraria (self), Advisory / Consultancy: Ipsen; Honoraria (self), Advisory / Consultancy: Novartis; Advisory / Consultancy: EUSA Pharma; Advisory / Consultancy: Eisai; Honoraria (institution), Advisory / Consultancy: Sanofi-Aventis; Honoraria (self): Lilly. M. Lázaro Quintela: Advisory / Consultancy: Bristol-Myers-Squibb; Advisory / Consultancy, Travel / Accommodation / Expenses: MSD Oncology; Advisory / Consultancy: Takeda; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Advisory / Consultancy, Travel / Accommodation / Expenses: Pfizer; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Ipsen; Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy: Boehringer Ingelheim; Advisory / Consultancy, Travel / Accommodation / Expenses: Pierre-Fabre; Advisory / Consultancy: Bayer; Honoraria (self): Lilly; Honoraria (self), Travel / Accommodation / Expenses: Astellas Pharma; Honoraria (self), Travel / Accommodation / Expenses: Janssen-Cilag; Honoraria (self): Novartis; Honoraria (self): Vifor. M.A. Climent Duran: Honoraria (self), Advisory / Consultancy: Bristol-Myers-Squibb; Honoraria (self), Travel / Accommodation / Expenses: Astellas Pharma; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Janssen-Cilag; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: MSD Oncology; Honoraria (self): Sanofi-Aventis; Honoraria (self), Advisory / Consultancy: Bayer; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Honoraria (self), Advisory / Consultancy: Pfizer; Honoraria (self): Novartis; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Ipsen; Advisory / Consultancy: EUSA Pharma; Advisory / Consultancy: Pierre-Fabre. J. Puente: Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Sanofi-Aventis; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Janssen-Cilag; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Astellas Pharma; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Pfizer; Advisory / Consultancy, Speaker Bureau / Expert testimony: Bayer; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Roche; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Ipsen; Advisory / Consultancy: Novartis; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Eisai; Advisory / Consultancy: EUSA Pharma; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Bristol-Myers-Squibb; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: MSD Oncology; Travel / Accommodation / Expenses: Pierre-Fabre. J. García Sánchez: Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche; Speaker Bureau / Expert testimony: Boehringer Ingelheim; Advisory / Consultancy: EUSA Pharma; Travel / Accommodation / Expenses: Bristol-Myers-Squibb; Travel / Accommodation / Expenses: MSD Oncology; Travel / Accommodation / Expenses: Pfizer. J. Carles: Research grant / Funding (institution): AB Science; Research grant / Funding (institution): Aragon Pharmaceuticals; Research grant / Funding (institution): Arog Pharmaceuticals, Inc.; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Astellas Pharma; Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca AB; Research grant / Funding (institution): Aveo Pharmaceuticals, Inc.; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Bayer AG; Research grant / Funding (institution): Blueprint Medicines Corporation; Research grant / Funding (institution): BN Immunotherapeuticals, Inc.; Research grant / Funding (institution): Boehringer Ingelheim España SA; Research grant / Funding (institution): Bristol-Myers-Squibb International Corporation; Research grant / Funding (institution): Clovis Oncology, Inc.; Research grant / Funding (institution): Cougar Biotechnology, Inc.; Research grant / Funding (institution): Deciphera Pharmaceuticals LLC; Research grant / Funding (institution): Exerelixis Inc.; Research grant / Funding (institution): F. Hoffmann-La Roche Ltd.; Research grant / Funding (institution): Genentech, INC; Research grant / Funding (institution): GlaxoSmithKline SA; Research grant / Funding (institution): Incyte Corporation; Research grant / Funding (institution): Janssen-Cilag International NV; Research grant / Funding (institution): Karyopharm Therapeutics Inc.; Research grant / Funding (institution): Laboratoires Leurquin Mediolanum SAS; Research grant / Funding (institution): Lilly SA; Research grant / Funding (institution): Medimmune; Travel / Accommodation / Expenses: Millennium Pharmaceuticals Inc.; Research grant / Funding (institution): Nanobiotix S.A.; Research grant / Funding (institution): Novartis Pharmaceutical SA; Research grant / Funding (institution): Pfizer SLU; Research grant / Funding (self): Puma Biotechnology, Inc.; Advisory / Consultancy, Research grant / Funding (institution): Sanofi-Aventis S.A.; Speaker Bureau / Expert testimony: SFJ Pharma Ltd.II; Research grant / Funding (institution): Teva Pharma SLU; Advisory / Consultancy: Bristol-Myers-Squibb; Advisory / Consultancy, Speaker Bureau / Expert testimony: Johnson and Johnson; Advisory / Consultancy: Pfizer; Advisory / Consultancy: MSD Oncology; Advisory / Consultancy: Roche; Speaker Bureau / Expert testimony: Asofarma. All other authors have declared no conflicts of interest.