AMPLITUDE: trial | Bending the Curve: Trial by Trial

AMPLITUDE

Niraparib with abiraterone acetate and prednisone versus placebo with abiraterone acetate and prednisone in metastatic castration-sensitive prostate cancer with homologous recombination repair gene alterations

Phase 3N = 696NCT04497844

Population

Metastatic castration-sensitive prostate cancer with HRR gene alterations (56% had BRCA1 or BRCA2 alterations; 78% had high-volume metastases; 16% had received docetaxel)

Design

Double-blind, randomised (1:1) phase 3 trial of niraparib plus abiraterone acetate and prednisone (AAP) versus placebo plus AAP in metastatic castration-sensitive prostate cancer with HRR gene alterations; androgen deprivation therapy had been started 14 days to 6 months before randomisation and was continued. The primary endpoint, investigator-assessed radiographic progression-free survival, was tested first in the BRCA subgroup (BRCA1 or BRCA2; n=387) and then in the intention-to-treat population; overall survival was a key secondary endpoint.

Primary endpoint

rPFS

Arms

Niraparib plus AAP (experimental, n = 348): Niraparib plus abiraterone acetate and prednisone
Placebo plus AAP (control, n = 348): Placebo plus abiraterone acetate and prednisone

People

Attard G

rPFSHR 0.52 (95% CI 0.37–0.72)rPFSHR 0.63 (95% CI 0.49–0.80)OSHR 0.79 (95% CI 0.59–1.04)rPFSHR 0.46 (95% CI 0.32–0.66)

Show the numbers

Results reported for AMPLITUDE
Endpoint	Analysis	Niraparib plus AAP	Placebo plus AAP	Effect
rPFSBRCA subgroup (BRCA1 or BRCA2; n=387)Investigator-assessed radiographic progression-free survival	primaryAttard 2025	—	median 26 months	HR 0.52 (95% CI 0.37–0.72)P<0.0001Median not reached at the time of analysis for niraparib plus AAP versus 26 months for placebo plus AAP.
rPFSInvestigator-assessed radiographic progression-free survival	primaryAttard 2025	—	—	HR 0.63 (95% CI 0.49–0.80)P=0.0001
OSHRR-altered population (n=696)	interimAttard 2025	—	—	HR 0.79 (95% CI 0.59–1.04)Immature: first interim analysis, 193 deaths of the 389 required for the final analysis (information fraction 50%). BRCA subgroup hazard ratio 0.75 (95% CI 0.51 to 1.11).
rPFSBRCA2-mutated subgroup (323 patients; exploratory, as described by the FDA)Investigator-assessed radiographic progression-free survival	exploratorySource 2025	—	median 26 months (18–28)	HR 0.46 (95% CI 0.32–0.66)Read from the FDA notice of 12 December 2025 (basis recorded as label; the field has no value for an FDA web notice). Median not estimable (95% CI 41 to not estimable) with niraparib plus AAP. For the 373 patients without a BRCA2 mutation the FDA gives a hazard ratio of 0.88 (95% CI 0.63 to 1.24).

Results reported for AMPLITUDE
Endpoint	Analysis	Niraparib plus AAP	Placebo plus AAP	Effect
rPFSBRCA subgroup (BRCA1 or BRCA2; n=387)Investigator-assessed radiographic progression-free survival	primaryAttard 2025	—	median 26 months	HR 0.52 (95% CI 0.37–0.72)P<0.0001Median not reached at the time of analysis for niraparib plus AAP versus 26 months for placebo plus AAP.
rPFSInvestigator-assessed radiographic progression-free survival	primaryAttard 2025	—	—	HR 0.63 (95% CI 0.49–0.80)P=0.0001
OSHRR-altered population (n=696)	interimAttard 2025	—	—	HR 0.79 (95% CI 0.59–1.04)Immature: first interim analysis, 193 deaths of the 389 required for the final analysis (information fraction 50%). BRCA subgroup hazard ratio 0.75 (95% CI 0.51 to 1.11).
rPFSBRCA2-mutated subgroup (323 patients; exploratory, as described by the FDA)Investigator-assessed radiographic progression-free survival	exploratorySource 2025	—	median 26 months (18–28)	HR 0.46 (95% CI 0.32–0.66)Read from the FDA notice of 12 December 2025 (basis recorded as label; the field has no value for an FDA web notice). Median not estimable (95% CI 41 to not estimable) with niraparib plus AAP. For the 373 patients without a BRCA2 mutation the FDA gives a hazard ratio of 0.88 (95% CI 0.63 to 1.24).

Hazard ratio (95% CI) by endpoint. Values below 1 favour the experimental arm.

Data table

Endpoint	HR	95% CI
rPFS	0.52	0.37–0.72
rPFS	0.63	0.49–0.8
OS	0.79	0.59–1.04
rPFS	0.46	0.32–0.66

Illustrative — modelled from reported values, not trial data. rPFS, primary.

Show curves

Placebo plus AAP (control)

Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.

Data table (modelled values)

Months	Placebo plus AAP
0	100.0%
16	65.3%
33	41.5%
49	27.1%
65	17.7%

Illustrative — modelled from reported values, not trial data. rPFS, exploratory.

Show curves

Placebo plus AAP (control)

Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.

Data table (modelled values)

Months	Placebo plus AAP
0	100.0%
16	65.3%
33	41.5%
49	27.1%
65	17.7%

Appears in

2025 Biomarker-selected mHSPC: AMPLITUDE (BRCA) and CAPItello-281 (PTEN)

Sources

Attard G, Agarwal N, Graff JN, Sandhu S, Efstathiou E, Özgüroğlu M, et al. Niraparib and abiraterone acetate plus prednisone for HRR-deficient metastatic castration-sensitive prostate cancer: a randomized phase 3 trial. Nat Med. 2025;31(12):4109-4118.
PubMed DOI
FDA. FDA approves niraparib and abiraterone acetate plus prednisone for BRCA2-mutated metastatic castration-sensitive prostate cancer. Notice, 12 December 2025.
Source