Clinical validity of FoundationOne CDx assay to identify <i>HRR</i> -positive or <i>BRCA</i> -positive mCSPC patients in the phase 3 AMPLITUDE study.

Abstract

166 Background: AMPLITUDE, a Phase 3, randomized, double-blind, placebo-controlled trial, evaluated the safety and efficacy of niraparib plus abiraterone acetate with prednisone (NIRA+AAP) in patients (pts) with homologous recombination repair-positive ( HRR +) mCSPC. Nira+AAP is indicated for BRCA + metastatic castration-resistant prostate cancer (mCRPC) pts, as identified by an approved companion diagnostic tissue (FoundationOne CDx (F1CDx). We evaluated the clinical utility of the tissue F1CDx test to identify HRR + or BRCA+ mCSPC pts in the AMPLITUDE study. Methods: HRR status was prospectively evaluated in AMPLITUDE pts utilizing central (tissue- F1CDx) and/or local tests as clinical trial assays (CTAs), and the efficacy of Nira+AAP was evaluated by the primary endpoint of radiographic progression-free survival (rPFS). Clinical utility of F1CDx was explored by comparing rPFS between treatment arms in HRR + and BRCA + pts identified by F1CDx and overall enrolled by CTAs in AMPLITUDE. Results: Out of 696 enrolled HRR+ pts, 549 (78.9%) were evaluated by F1CDx assay. Out of 549 pts, 468 (85.2%) were HRR + (including 273 [49.7%] BRCA + pts), 81 (14.7%) were neg. The Hazard Ratio (HR) of rPFS in HRR + pts identified by F1CDx was 0.56 (95% 2-sided Confidence Interval (CI): 0.42,0.76) vs overall HRR+ pts in the study 0.62 (95% CI: 0.49, 0.79). In BRCA + pts identified by F1CDx, the HR was 0.46 (95% 2-sided CI: 0.30, 0.69) vs overall BRCA + 0.515 (95% CI: 0.37, 0.717). Conclusions: Clinical efficacy of NIRA+AAP was consistent in F1CDx-identified HRR + or BRCA + pts compared with the overall patient population in AMPLITUDE, demonstrating the clinical utility of the F1CDx assay to identify HRR + or BRCA + mCSPC patients to help guide treatment decision regarding NIRA+AAP. Clinical trial information: NCT04497844 .