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Background: MAGNITUDE Phase 3 Study

• Up to 30% of patients have mCRPC with alterations in genes associated with HRR (e.g.

BRCA2), which have been associated with poor prognosis but confer sensitivity to PARP

inhibiton 1-10

• Androgen receptor (AR) signaling regulates DNA repair in prostate cancer, providing a

rationale for combined AR targeting with PARP inhibition 11

• Niraparib, a potent inhibitor of PARP1 and PARP2, has anti-tumour activity in heavily

pretreated patients with HRR-gene altered mCRPC 6

• The Phase 3 MAGNITUDE study was initiated to assess the combination of niraparib and AAP

for mCRPC in prospectively selected patients with and without alterations in HRR associated

genes

AAP, abiraterone acetate + prednisone/prednisolone; DNA, deoxyribonucleic acid; HRR, homologous recombination repair; HRR, homologous recombination repair; mCRPC, metastatic castration-resistant prostate cancer; OS, overall survival; PARP, poly adenosine diphosphate–
ribose polymerase.
1. Pritchard CC, et al. N Engl J Med 2016;375:443-453. 2. Robinson D, et al. Cell 2015;161:1215-1228. 3. Cui M, et al. Clin Cancer Res. 2017;8(25):40222-40232. 4. Castro E, et al. J Clin Oncol. 2019;37(6):490-503. 5. Annala M, et al. Cancer Discov. 2018;8(4):444-457. 6. Smith
MR, et al. Lancet Oncol. 2022;[In press]. 7. Hussain M, et al. N Engl J Med. 2020;383:2345-2357. 8. de Bono JS, et al. Lancet Oncol. 2021;22:1250-1264. 9. Abida W, et al. J Clin Oncol. 2020;38:3763-3772. 10. Abida W, et al. Clin Cancer Res. 2020;26:2487-2496. 11. Polkinghorn
WR, et al. Cancer Discov 2013;3:1245-1253.

PRESENTED BY: Kim N. Chi, MD