LBA50Pre-specified interim analysis of GALAHAD: A phase II study of niraparib in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) and biallelic DNA-repair gene defects (DRD)

Abstract Background Effective therapies for pts with treatment-refractory mCRPC are an important unmet medical need. Niraparib is a highly selective poly ADP-ribose polymerase (PARP) inhibitor of PARP-1 and PARP-2 DNA-repair polymerases. Methods GALAHAD is an ongoing open-label phase II study assessing niraparib (300 mg daily) in pts with mCRPC and DRD with disease progression on taxane and androgen receptor-targeted therapy. DRD status was evaluated by a plasma or tissue-based test and defined as having biallelic alterations in BRCA1/2 (BRCA), ATM, FANCA, PALB2, CHEK2, BRIP1, or HDAC2. Primary endpoint was objective response rate (ORR) by RECIST 1.1 with no evidence of bone progression as per the PCWG3 criteria. Composite response rate (CRR) was defined as ORR, conversion of circulating tumor cells to  Results As of 23 May 2019, 165 pts were enrolled, of whom 81 had biallelic DRD (46 BRCA and 35 non-BRCA) and had a minimum of 16 weeks of follow up. 51/81 had measurable disease at baseline (29 BRCA and 22 non-BRCA); 47% of pts had visceral metastases. Median follow-up in BRCA and non-BRCA was 7.3 and 6.4 mo, respectively. In BRCA, ORR was 41% and CRR was 63% (table); median duration of objective response was 5.5 mo (range: 3.5–9.2). 7/12 BRCA responses were ongoing. Median rPFS and OS in BRCA were 8.2 and 12.6 mo, respectively. In non-BRCA, objective response was noted in 2/22 pts (both had FANCA) and CRR was 17%; durations of objective response were 3.8 and 6.5 mo, respectively. Grade 3/4 treatment-emergent adverse events were mostly hematologic—anemia (29%), thrombocytopenia (15%) and neutropenia (7%)—and managed with dose interruption or modification. Conclusions Niraparib demonstrates clinical activity in pts with treatment-refractory mCRPC with durable responses particularly in biallelic BRCA mutation carriers. Table . LBA50 All biallelic DRD (n = 81) Response BRCA1/2 Non-BRCA n (%) (95% CI) (n = 46) (n = 35) Objective RR 12/29 (41) (23.5, 61.1) 2/22 (9) (1.1, 29.2) PSA50 23/46 (50) (34.9, 65.1) 1/35 (3) (0.1, 14.9) CTC Conversion 18/38 (47) (31.0, 64.2) 5/24 (21) (7.1, 42.2) CRR 29/46 (63) (47.6, 76.8) 6/35 (17) (6.6, 33.7) Median rPFS, mo (95% CI) 8.2 (5.2, 11.1) 5.3 (1.9, 5.7) Median OS, mo (95% CI) 12.6 (9.2, 15.7) 14.0 (5.3, 20.1) CI, confidence interval; CRR, composite response rate; CTC, circulating tumor cells; DRD, DNA-repair gene defects; ORR, objective response rate; OS, overall survival; PSA50, ≥50% decline in prostate-specific antigen; rPFS, radiographic progression-free survival. Clinical trial identification NCT02854436. Editorial acknowledgement Writing assistance was provided by Ramji Narayanan of SIRO Clinpharm Pvt Ltd and funded by Janssen Global Services, LLC. Legal entity responsible for the study Janssen Research & Development, LLC. Funding Janssen Research & Development, LLC. Disclosure S.K. Sandhu: Honoraria (self), Advisory / Consultancy: Amgen; Honoraria (self), Speaker Bureau / Expert testimony: Bristol-Myers Squibb; Honoraria (self), Speaker Bureau / Expert testimony: Merck. W.K. Kelly: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Sanofi; Research grant / Funding (institution): Janssen; Research grant / Funding (institution): Novartis. H.I. Scher: Leadership role, Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options: Asterias Biotherapeutics; Advisory / Consultancy: Ambry Genetics Corporation; Advisory / Consultancy: Konica Minolta,Inc; Advisory / Consultancy: Janssen Biotech, Inc; Advisory / Consultancy, Research grant / Funding (institution): Janssen Research & Development; Advisory / Consultancy, Travel / Accommodation / Expenses: OncLive Insights; Advisory / Consultancy: Physician Education Resource; Advisory / Consultancy, Travel / Accommodation / Expenses: Sanofi; Advisory / Consultancy, Travel / Accommodation / Expenses: WIRB-Copernicus Group; Research grant / Funding (institution): Illumina ; Research grant / Funding (institution): Innocrin Pharma; Travel / Accommodation / Expenses: Physician Education Resource. E. Efstathiou: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Janssen-Cilag; Honoraria (self), Research grant / Funding (institution): Sanofi; Honoraria (self), Advisory / Consultancy: Takeda; Advisory / Consultancy, Research grant / Funding (institution): Astellas Pharma; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Bayer; Advisory / Consultancy: Innocrin Pharma; Advisory / Consultancy: MSD; Advisory / Consultancy: Tolmar. P.N. Lara: Honoraria (self), Advisory / Consultancy: Pfizer; Advisory / Consultancy: AbbVie; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Bayer; Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy: CellMax Life; Advisory / Consultancy: Exelixis; Advisory / Consultancy: Foundation Medicine; Advisory / Consultancy: Genentech/Roche; Advisory / Consultancy: Janssen; Advisory / Consultancy, Research grant / Funding (institution): Merck; Advisory / Consultancy: Nektar; Advisory / Consultancy: Turnstone Bio; Research grant / Funding (institution): Aragon Pharmaceuticals; Research grant / Funding (institution): Genentech ; Research grant / Funding (institution): GlaxoSmithKline ; Research grant / Funding (institution): Heat Biologics; Research grant / Funding (institution): Incyte ; Research grant / Funding (institution): Janssen Biotech; Research grant / Funding (institution): Millennium, Pharmacyclics, Polaris,TRACON Pharma . E.Y. Yu: Advisory / Consultancy: Amgen; AstraZeneca; Bayer; Churchill Pharmaceuticals; EMD Serono; Incyte; Janssen; Merck; QED; Tolmar; Research grant / Funding (institution): Agensys; Astellas Pharma; Bayer; Dendreon; Genentech/Roche; Merck; Seattle Genetics. D.J. George: Honoraria (self): Bayer; Exelixis; Sanofi; Advisory / Consultancy: Astellas Pharma; Bayer; Bristol-Myers Squibb; Exelixis; Genentech; Innocrin Pharma; Janssen; Merck Sharp & Dohme; Myovant Sciences; Pfizer; Sanofi; Speaker Bureau / Expert testimony: Bayer; Exelixis; Sanofi; Research grant / Funding (institution): Acerta Pharma ; Astellas Pharma ; Bayer ; Bristol-Myers Squibb ; Dendreon ; Exelixis ; Innocrin Pharma ; Janssen Oncology ; Novartis ; Pfizer ; Travel / Accommodation / Expenses: Bayer; Exelixis; Merck; Pfizer; Sanofi. K.N. Chi: Honoraria (self): Astellas Pharma; Bayer; Janssen; Sanofi; Advisory / Consultancy: Amgen; Astellas Pharma; Bayer; ESSA; Janssen; Lilly/ImClone; Sanofi; Research grant / Funding (institution): Astellas Pharma ; Bayer ; Bristol-Myers Squibb ; Janssen ; Lilly/ImClone ; Merck ; Roche ; Sanofi ; Tokai Pharmaceuticals . F. Saad: Honoraria (self): Astellas Pharma; AstraZeneca; Bayer; Janssen Oncology; Sanofi; Advisory / Consultancy: Astellas Pharma; AstraZeneca/MedImmune; Bayer; Janssen Oncology; Sanofi; Research grant / Funding (institution): Astellas Pharma ; AstraZeneca ; Bayer ; Janssen Oncology ; Sanofi . J. Summa: Shareholder / Stockholder / Stock options, Full / Part-time employment: Janssen. J.M. Freedman: Shareholder / Stockholder / Stock options, Full / Part-time employment: Janssen. G.E. Mason: Shareholder / Stockholder / Stock options, Full / Part-time employment: Janssen. E. Zhu: Full / Part-time employment: Janssen. D. Ricci: Shareholder / Stockholder / Stock options, Full / Part-time employment: Janssen. J.S. Simon: Shareholder / Stockholder / Stock options, Full / Part-time employment: Janssen. S. Cheng: Shareholder / Stockholder / Stock options, Full / Part-time employment: Janssen. All other authors have declared no conflicts of interest.