Phase 3 AMPLITUDE trial — a pivotal study evaluating the combination of niraparib (a PARP inhibitor) and abiraterone acetate plus prednisone in patients with metastatic castration-sensitive prostate cancer (mCSPC) who have homologous recombination repair (HRR) gene mutations.
Key Details of the AMPLITUDE Trial
- Design & Scope
- Phase 3, randomized, double-blind, placebo-controlled, international, multicenter trial (NCT04497844).
- Planned enrollment: approximately 788 patients across ~352 sites in 32 countries.
- Primary Endpoint
- Radiographic progression-free survival (rPFS) — time until radiographic tumor progression or death.
- Key Findings (as of June 2025)
- The trial met its primary endpoint, demonstrating a significant reduction in progression risk. Specifically, a 37% reduction in risk of radiographic progression or death with the niraparib combination versus placebo + AAP.
- Time to symptomatic progression was also significantly delayed — a meaningful patient-centered outcome.
- Overall survival (OS) data are maturing but showing favorable trends.
- Safety Profile
- No new safety signals identified.
- Grade 3 or 4 adverse events (AEs) occurred more often in the treatment arm (75.2%) than placebo (58.9%), with notable toxicities including anemia (29.1% vs. 4.6%) and hypertension (26.5% vs. 18.4%).
- Discontinuations were low: 11.0% in the niraparib arm vs 6.9% in placebo—so a difference of under 5%.
Summary
The AMPLITUDE Phase 3 trial is a landmark study showing that adding a PARP inhibitor (niraparib) to standard androgen-receptor pathway inhibition can meaningfully delay disease progression in HRR-mutated mCSPC. With strong efficacy in rPFS, extended time to symptomatic progression, and emerging OS data — alongside a manageable safety profile — these results could pave the way for a new treatment standard in this patient population.