SUMMARY  

• AMPLITUDE (NCT04497844) is an ongoing, phase 3, randomized, double-blind, placebo-controlled, multicenter, global study evaluating the efficacy and safety of niraparib and abiraterone acetate (AA) in a dual-action tablet (DAT) formulation with prednisone plus androgen deprivation therapy (ADT) compared to matching oral placebo/abiraterone acetate in a DAT formulation with prednisone plus ADT in patients with deleterious germline or somatic homologous recombination repair (HRR) gene-altered metastatic castration-sensitive prostate cancer (mCSPC; N=696).^1-4
  • The primary endpoint of radiographic progression-free survival (rPFS) in the AKEEGA plus prednisone group vs placebo/abiraterone acetate plus prednisone (AAP) group was met:⁴ 
    • BRCAm subgroup: NE vs 26.0 months; HR, 0.52; 95% CI, 0.37-0.72; P<0.0001
    • HRRm population: NE vs 29.5 months; HR, 0.63; 95% CI, 0.49-0.80; P=0.0001
  • A summary of treatment-emergent adverse events (TEAEs) is described in Table: Adverse Events. In the AKEEGA vs placebo/AAP group, treatment-related TEAEs and TEAEs leading to discontinuation were reported in 89% vs 74% and 15% vs 10% of patients, respectively. The most common AEs of interest were anemia (52% vs 24%) and hypertension (45% vs 33%), respectively.⁴ 

CLINICAL DATA

AMPLITUDE Study

Attard et al (2025)⁴ reported efficacy and safety results of AKEEGA plus ADT vs placebo/AAP plus ADT in patients with deleterious germline or somatic HRR gene-altered mCSPC (N=696).

Study Design/Methods

• Phase 3, randomized, double-blind, placebo-controlled, multicenter, global study
• The study design is presented in Figure: AMPLITUDE Study Design.
• The HRR effectors group (BRCA1/2 + BRIP1, PALB2, RAD51B, RAD54L) are prespecified for formal statistical analysis after BRCAm and prior to HRRm.
  • BRCA1/2 alterations include co-occurring BRCA1 or BRCA2 alterations.

Results

Patient Characteristics

• Patient characteristics were well balanced between the 2 groups (Table: Select Baseline Patient and Disease Characteristics - HRRm (ITT) Population).

Efficacy

• A summary of study results is provided in Table: Primary and Secondary Endpoint Results. The median follow-up was 30.8 months (data cutoff: January 7, 2025).
• Subgroup analyses by alteration type are summarized in Table: Subgroup Analysis by BRCA and non-BRCA Alterations.
• The treatment effect of AKEEGA with prednisone vs placebo/AAP on median rPFS in the HRRm population was generally consistent across several prespecified subgroups, including patients with high-volume disease at baseline (41.2 months [events/N, 100/269] vs 26.3 months [130/271]; HR, 0.65; 95% CI, 0.50-0.85) and M1 disease at diagnosis (NE [100/301] vs 27.4 months [142/302]; HR, 0.60; 95% CI, 0.47-0.78).
• At data cutoff, 93 (27%) patients in the AKEEGA group vs 149 (43%) patients in the placebo/AAP discontinued treatment due to progressive disease. Subsequent therapies used are provided in Table: Subsequent Therapy.

Safety

• A summary of AEs reported in both treatment arms is shown in Table: Adverse Events. Other common AEs of any grade included constipation (35% vs 16%), nausea (31% vs 14%), fatigue (26% vs 18%), and arthralgia (21% each), in the AKEEGA vs PBO/AAP groups, respectively.

Literature Search

A literature search of MEDLINE^®, Embase^®, BIOSIS Previews^®, and Derwent Drug File (and/or other resources, including internal/external databases) was conducted on 19 May 2025.