2892 - A phase 3 randomized, placebo-controlled, double-blind study of niraparib plus abiraterone acetate and prednisone versus abiraterone acetate and prednisone in patients with metastatic prostate cancer (NCT03748641)

Background

Preclinical data suggest synergistic antitumor activity when a PARP inhibitor (PARPi) is combined with an androgen pathway inhibitor. The addition of a PARPi to abiraterone acetate and prednisone (AAP) shows improved radiographic progression-free survival (rPFS) versus AAP alone in patients with mCRPC regardless of the presence of DNA repair gene defects (DRD).¹ Interim results from a phase 1 study² support safety and tolerability of a combination of niraparib 200 mg plus AAP in patients with mCRPC. The objective of this Phase 3 study is to compare the efficacy and safety of niraparib plus AAP versus AAP with placebo as first-line therapy for mCRPC.

Trial design

The multicenter global MAGNITUDE study will open in 300 sites and 28 countries and will enroll patients with mCRPC untreated with other than ongoing androgen deprivation therapy [ADT] and ≤4 months of exposure to AAP. Cohort 1 (n = 400) will comprise patients whose tumors have DRD, as determined by either a blood or tissue assay. Cohort 2 (n = 600) will enroll patients whose tumors are not DRD +ve. Enrollment began in February 2019. The primary objective of the study is to compare radiographic progression-free survival (rPFS) for patients treated with niraparib and AAP versus AAP and placebo as first-line therapy for mCRPC. To test superiority of combination vs AAP, sample sizes were estimated to provide ≥92% power to detect HR ≤ 0.67 in the two cohorts at a 2-tailed level of significance of 0.05. Major secondary objectives are to assess the effect of the combination treatment on overall survival, time to chronic opioid use, time to pain progression and time to cytotoxic chemotherapy. Safety and pharmacokinetic profiles will be evaluated.

Clinical trial identification

NCT03748641.

Editorial acknowledgement

Ann C Sherwood, PhD with funding from Janssen Pharmaceuticals.

Legal entity responsible for the study

Janssen Pharmaceuticals.

Funding

Janssen Pharmaceuticals.

Disclosure

K.N. Chi: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Sanofi; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Janssen; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Astellas; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Bayer; Advisory / Consultancy: ESSA; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy, Research grant / Funding (institution): Roche; Advisory / Consultancy: Amgen; Research grant / Funding (institution): Tokai; Research grant / Funding (institution): Lilly/ImClone; Research grant / Funding (institution): Bristol-Meyers Squibb; Research grant / Funding (institution): Merck. D. Rathkopf: Research grant / Funding (institution): Tracon Pharma; Research grant / Funding (institution): Genentech Roche; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Taiho Pharmaceuticals; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Ferring; Research grant / Funding (institution): Millennium; Research grant / Funding (institution): Takeda; Research grant / Funding (institution): Celgene; Research grant / Funding (institution): Medivation; Research grant / Funding (institution): Janssen Oncology. G. Attard: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Janssen; Advisory / Consultancy: Veridex; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Roche Ventana; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Astellas; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Novartis; Advisory / Consultancy: Millennium; Advisory / Consultancy, Travel / Accommodation / Expenses: Abbott; Advisory / Consultancy, Travel / Accommodation / Expenses: Essa; Advisory / Consultancy, Travel / Accommodation / Expenses: Bayer; Speaker Bureau / Expert testimony: Takeda; Speaker Bureau / Expert testimony: Sanofi Aventis. M.R. Smith: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Amgen; Honoraria (self), Advisory / Consultancy: Astellas; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Bayer; Honoraria (institution), Advisory / Consultancy: Clovis; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Gilead; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Janssen; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Lilly; Honoraria (self), Advisory / Consultancy: Novartis; Honoraria (self), Advisory / Consultancy: Pfizer. E. Efstathiou: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Travel / Accommodation / Expenses: Janssen; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self), Travel / Accommodation / Expenses: Sanofi; Advisory / Consultancy, Travel / Accommodation / Expenses: Oric Pharma; Advisory / Consultancy: Bayer; Advisory / Consultancy: Tolmar; Research grant / Funding (self): Astellas; Research grant / Funding (self): Pfizer. D. Olmos: Advisory / Consultancy, Research grant / Funding (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: AstraZeneca; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Bayer; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Research grant / Funding (institution): Janssen Oncology; Advisory / Consultancy: Clovis; Travel / Accommodation / Expenses: Ipsen; Research grant / Funding (self), Research grant / Funding (institution): Genentech. E.J. Small: Advisory / Consultancy, Shareholder / Stockholder / Stock options: Fortis Therpeutics; Shareholder / Stockholder / Stock options: Harpoon Therapeutics; Honoraria (self), Advisory / Consultancy: Janssen; Advisory / Consultancy: Beigene. P. Sieber: Speaker Bureau / Expert testimony, Research grant / Funding (self): Astellas; Speaker Bureau / Expert testimony, Research grant / Funding (self): Pfizer; Speaker Bureau / Expert testimony, Research grant / Funding (self): Dendreon; Research grant / Funding (self): Janssen; Research grant / Funding (self): Allergan; Research grant / Funding (self): Effector; Research grant / Funding (self): Myovant; Research grant / Funding (self): Eli Lilly; Research grant / Funding (self): Hinova; Research grant / Funding (self): Merck. C. Dunshee: Advisory / Consultancy, Research grant / Funding (institution): Pfizer; Advisory / Consultancy, Research grant / Funding (institution): Ferring; Advisory / Consultancy: Sanofi Genzyme; Research grant / Funding (institution): Astellas Medivation; Research grant / Funding (institution): Janssen Oncology; Research grant / Funding (institution): Dendreon; Research grant / Funding (institution): Eleven Biotherapeutics; Research grant / Funding (institution): Myovant Sciences; Research grant / Funding (institution): Siemens; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Exact Sciences; Research grant / Funding (institution): TesoRx Pharmaceuticals. D. Ricci: Shareholder / Stockholder / Stock options, Full / Part-time employment: Janssen. J.S. Simon: Shareholder / Stockholder / Stock options, Full / Part-time employment: Janssen. X. Zhao: Shareholder / Stockholder / Stock options, Full / Part-time employment: Janssen. N. Kothari: Shareholder / Stockholder / Stock options, Full / Part-time employment: Janssen. S. Cheng: Shareholder / Stockholder / Stock options, Full / Part-time employment: Janssen. S.K. Sandhu: Honoraria (self), Research grant / Funding (institution): Merck Serono; Honoraria (self): Merck Sharp & Dohme; Honoraria (self): Roche/Genentech; Honoraria (self), Research grant / Funding (institution): Bristol-Myers Squibb; Honoraria (self), Travel / Accommodation / Expenses: Janssen; Research grant / Funding (institution), Travel / Accommodation / Expenses: Merck; Research grant / Funding (institution): Amgen; Research grant / Funding (institution): Tolmar. All other authors have declared no conflicts of interest.