1806P - Efficacy of niraparib and abiraterone acetate plus prednisone (NIRA+AAP) in homologous recombination repair gene-altered (HRR+) metastatic castration-resistant prostate cancer (mCRPC) by tissue and/or plasma assays in the MAGNITUDE trial

Background

The randomized, double-blind, phase 3 MAGNITUDE study evaluated NIRA+AAP vs placebo and AAP (PBO+AAP) as 1st line therapy for mCRPC that was HRR+ based on targeted next-generation sequencing of tumor tissue and/or plasma-based assays.¹ Here we aimed to assess treatment efficacy by assay.

Methods

Tumor tissue and/or plasma was collected from mCRPC patients (pts) who consented to the pre-screening protocol and tested using local tissue assays or centrally using the Foundation Medicine FoundationOne®CDx (F1CDX®) tissue assay or Agilent-Resolution Bioscience Resolution HRD™ Plasma assay. Pts HRR+ (BRCA1, BRCA2, FANCA, PALB2, CHEK2, BRIP1, HDAC2, ATM, CDK12) were randomized 1:1 to receive NIRA+AAP or PBO+AAP (NCT03748641). Primary (radiographic progression-free survival, rPFS) and secondary end-points (time to cytotoxic chemotherapy, TCC; time to symptomatic progression, TSP; and overall survival, OS) are reported for interim analysis 2 for each subgroup (events [NIRA+AAP/PBO+AAP], Hazard ratio and 95% CI).

Results

Overall, 423 pts were HRR+ with 225 BRCA+. Pts, 159 (96), were HRR+ (BRCA+) with both assays, the remaining pts were positive with either tissue/plasma (Table). Pts, 124 (62) HRR+ (BRCA+), were tissue positive but plasma negative, and 38 (17) HRR+ (BRCA+) pts were positive with plasma, but tissue negative. Hazard ratios for end-points, except OS, had p<0.05 for pts BRCA positive by either assay, with similar results for HRR+ pts.

Table: 1806P

Conclusions

Clinically meaningful benefit from NIRA+AAP are similar for BRCA+ pts detected by either tissue or plasma-based assays. Positivity by either test is sufficient to guide treatment decisions. 1. Efstathiou E, et al. J Clin Oncol. 2023;41(suppl 6):170.

Clinical trial identification

NCT03748641.

Editorial acknowledgement

Legal entity responsible for the study

Janssen Research & Development, LLC.

Funding

Janssen Research & Development, LLC.

Disclosure

G. Attard: Financial Interests, Personal, Invited Speaker: Janssen, Astellas, AstraZeneca; Financial Interests, Personal, Advisory Board: Janssen, Astellas, Novartis, Bayer, AstraZeneca, Pfizer, Sanofi, Sapience, Orion, Novartis; Financial Interests, Personal, Royalties, Included in list of rewards to discoverers of abiraterone: Institute of Cancer Research; Financial Interests, Institutional, Invited Speaker: Artera, Veracyte, Janssen, Novartis, Pfizer; Financial Interests, Institutional, Research Grant: Janssen, Astellas, Novartis; Non-Financial Interests, Principal Investigator: Janssen, Astellas; Non-Financial Interests, Advisory Role: Janssen, AstraZeneca; Non-Financial Interests, Project Lead: Artera, Veracyte. S.K. Sandhu: Financial Interests, Institutional, Advisory Board, I have served on advisory boards for BMS. The contracts for my role are set up with the institution and the funds go to a research fund at Peter MacCallum Cancer Centre: BMS; Financial Interests, Institutional, Advisory Board, I have served on advisory boards for MSD. The e contracts for my role are set up with the institution and the funds go to a research fund at Peter MacCallum Cancer Centre: Merck Sharp and Dohme; Financial Interests, Institutional, Advisory Board, I have served on advisory boards for AstraZeneca. The contracts for my role as an advisor are set up with the institution and the funds go to a research fund at Peter MacCallum Cancer Centre: AstraZeneca; Financial Interests, Institutional, Advisory Board, I have served on advisory boards for Novartis. The contracts for my role as an advisor are set up with the institution and the funds go to a research fund at Peter MacCallum Cancer Centre: Novartis; Financial Interests, Institutional, Advisory Board, I have served on an advisory board for Merck Serono. The contracts for my service are set up with the institution and funds go into a research fund at the Peter MacCallum Cancer Centre: Merck Serono; Financial Interests, Institutional, Research Grant, My institution receives grant funding to run an investigator initiated trial that I lead: Novartis, Genentech, Amgen, AstraZeneca, Merck Serono, Merck Sharp and Dohme; Financial Interests, Institutional, Funding, Pfizer are providing funding to my institution for the conduct of an investigator initiated clinical trial: Pfizer; Non-Financial Interests, Principal Investigator, I am a principal investigator on several of Janssen sponsored studies and don't receive any renumeration for this: Janssen; Non-Financial Interests, Principal Investigator, I am a principal investigator on several Novartis sponsored studies and don’t receive any renumeration for this: Novartis; Non-Financial Interests, Principal Investigator, I am a principal investigator on several of Genentech sponsored studies and don't receive any renumeration for this: Genentech; Non-Financial Interests, Principal Investigator, I am a principal investigator on several of BMS sponsored studies and don't receive any renumeration for this: BMS; Non-Financial Interests, Other, I serve on the Independent Safety and Data Monitoring committee for 2 of Novartis sponsored studies and don’t receive any compensation for this: Novartis; Non-Financial Interests, Principal Investigator, I am the Principal Investigator for several AstraZeneca sponsored studies and am not remunerated for this: AstraZeneca; Non-Financial Interests, Other, I serve on the steering committee for several Janssen sponsored trials and i do not receive compensation for this: Janssen; Non-Financial Interests, Other, I serve on the steering committee for one AstraZeneca sponsored trial and I do not receive compensation for this: AstraZeneca; Non-Financial Interests, Other, I serve on the steering committee for one Genentech sponsored trials and I do not receive compensation for this: Genentech; Non-Financial Interests, Other, I serve on the steering committee for a BMS sponsored trial and I do not receive renumeration for this: BMS. D. Rathkopf: Financial Interests, Trial Chair: Janssen; Financial Interests, Steering Committee Member: Janssen, Genentech; Financial Interests, Institutional, Research Grant, Clinical Trial Grant: Genentech; Non-Financial Interests, Advisory Role: Janssen, Genentech, AstraZeneca, Myovant, Bayer, BMS; Non-Financial Interests, Principal Investigator: Janssen, Genentech, Promontory, Celgene/BMS. E. Castro: Financial Interests, Personal, Advisory Board: Astellas, AstraZeneca, Janssen, MSD, Bayer, Pfizer; Financial Interests, Personal, Invited Speaker: Astellas, AstraZeneca, Janssen, Clovis, Pfizer; Financial Interests, Personal, Writing Engagement: Pfizer; Financial Interests, Institutional, Funding: AstraZeneca, Pfizer; Financial Interests, Institutional, Research Grant: Janssen, Bayer; Financial Interests, Institutional, Local PI: Janssen, Pfizer. M. Saad: Financial Interests, Speaker, Consultant, Advisor: AstraZeneca, BMS, Janssen, Merck, MSD, Novartis, Viatris; Financial Interests, Research Funding: Janssen, MSD; Financial Interests, Other, Honoraria: Amgen, Astellas, Cipla, Eisai, Ipsen, Pfizer. M.R. Smith: Financial Interests, Speaker, Consultant, Advisor: Amgen, Astellas, Bayer, Janssen, Lilly, Novartis, Pfizer; Financial Interests, Institutional, Research Funding: Bayer, ESSA, Janssen, Lilly, ORIC. E.J.J. Small: Financial Interests, Speaker, Consultant, Advisor: Fortis, Janssen, Teon Therapeutics; Financial Interests, Stocks/Shares: Fortis, Harpoon Therapeutics, Teon Therapeutics. D. Olmos: Financial Interests, Institutional, Advisory Role: AstraZeneca, Bayer, Janssen; Financial Interests, Speaker, Consultant, Advisor: Bayer, Clovis, Daiichi Sankyo, Janssen, MSD; Financial Interests, Institutional, Research Funding: Astellas, AstraZeneca, Bayer, Genentech/Roche, Janssen, MSD, Pfizer, Tokai. A.J.P.D.S. Gomes: Financial Interests, Speaker’s Bureau: Astellas, Bayer, Janssen; Financial Interests, Research Funding: AstraZeneca, Bayer, Janssen, MSD, Roche; Financial Interests, Advisory Role: Janssen; Financial Interests, Other, Honoraria: Astellas, AstraZeneca, Bayer, Janssen. G. Roubaud: Financial Interests, Speaker, Consultant, Advisor: Astellas, Janssen, MSD, Pfizer; Financial Interests, Research Funding: Bayer. B. Zurawski: Financial Interests, Speaker, Consultant, Advisor: Astellas, Roche; Financial Interests, Funding: BMS, GSK, Janssen, MSD, Merck Serono, Novartis, Roche. E. Efstathiou: Financial Interests, Speaker, Consultant, Advisor: Astellas, AstraZeneca, MSD, Myovant, Pfizer, Sanofi; Financial Interests, Research Funding: Astellas, AstraZeneca, MSD, Myovant, Pfizer, Sanofi. D. Wu, B. Diorio, K. Urtishak, U. Singh, Y. Xu, A. Lopez-Gitlitz, A. del Corral: Financial Interests, Full or part-time Employment: Janssen; Financial Interests, Stocks/Shares: Janssen. K.N.N. Chi: Financial Interests, Personal, Invited Speaker: Astellas, AstraZeneca, Janssen, Point Biopharma, Roche; Financial Interests, Personal, Advisory Board: AstraZeneca, AstraZeneca, Janssen, Merck, Novartis, Pfizer, Point Biopharma, Roche, BMS; Financial Interests, Institutional, Steering Committee Member: AstraZeneca, Janssen, Novartis, Roche; Financial Interests, Institutional, Trial Chair: AstraZeneca, Arvinas, Janssen, Novartis; Financial Interests, Institutional, Local PI: Arvinas.