Johnson & Johnson Announces Breakthrough Phase 3 AMPLITUDE Trial Results: Niraparib Combination Therapy Halves Cancer Progression Risk in HRR-Mutated mCSPC

Johnson & Johnson today announced the first results of its Phase 3 AMPLITUDE study. The study evaluates its PARP inhibitor niraparib in combination withAbiraterone AcetateAnd prednisone (AAP) in carriers of homologous recombination repair (HRR) gene mutations (includingBRCA) in patients with metastatic castration-sensitive prostate cancer (mCSPC). The results showed,This combination regimen demonstrated clinically significant and statistically meaningful improvements in radiographic progression-free survival (rPFS) and time to symptomatic progression (TSP), and preliminarily showed a trend toward overall survival (OS) improvement., highlighting the potential of this treatment combination in delaying disease progression and symptom deterioration. According to the press release,This is the first Phase 3 study in which a PARP inhibitor combined with other treatments has demonstrated clinical improvement in patients with mCSPC.

AMPLITUDE is an ongoing international multicenter, randomized, double-blind, placebo-controlled Phase 3 study designed to evaluate Akeega (niraparib withAbiraterone AcetateThe efficacy and safety of dual-mechanism combination tablets [DAT] in conjunction with prednisone and androgen deprivation therapy (ADT). The control group received matched placebo/Abiraterone AcetateCombined with prednisone and ADT. The study included 696 mCSPC patients with HRR gene mutations. The primary endpoint was radiographic progression-free survival.

Analysis shows that the trial reached the primary endpoint of rPFS. InBRCAIn mutation patients (n=191), niraparib combination therapy demonstrated significant benefits,The median rPFS for patients has not been reached, while it was 26 months for the control group, with a 48% reduction in the risk of radiographic disease progression or death (HR=0.52; 95% CI: 0.37-0.72, p<0.0001).In all patients with HRR mutations, the median rPFS was not reached in the niraparib combination therapy group, while the median rPFS in the control group was 29.5 months, with a 37% reduction in the risk of disease progression or death (HR=0.63; 95% CI: 0.49-0.80, p=0.0001).

In addition,InBRCAIn patients with mutations, niraparib combination therapy reduced the risk of symptom progression by 56% (HR=0.44).；95% CI：0.29-0.68，p=0.0001）, it was reduced by 50% in all patients with HRR mutations (HR=0.50; 95% CI: 0.36-0.69, p<0.0001),This means that the time before patients experience symptom deterioration and need to undergo radiotherapy, surgery, or a new round of anti-tumor treatment is significantly extended.

Image Source: 123RF

The analysis also shows,Niraparib Combination Therapy WillBRCAThe risk of death in patients with mutations was reduced by 25% (HR=0.75).；95% CI：0.51-1.11，p=0.15）, it decreased by 21% in all patients with HRR mutations (HR=0.79; 95% CI: 0.59-1.04, p=0.10), showing a potential preliminary trend of overall survival benefit for niraparib combination therapy. The trial is still ongoing for more mature data.

In terms of safety, grade 3/4 adverse events (AEs) were more common in the niraparib combination therapy group (75% vs. 59%), with anemia and hypertension being the most frequent adverse reactions; however, the discontinuation rate due to adverse events remained low (14.7% vs. 10.3%). To date, niraparib in combinationAbiraterone AcetateThe safety profile of prednisone was consistent with previous studies.

Image Source: 123RF

Dr. Charles Drake, Vice President of Johnson & Johnson's Innovative Medicine Division for Prostate Cancer and Immunotherapy, stated: "The AMPLITUDE study aims to evaluate the duration patients can remain stable during the stage when their cancer has not yet progressed. We found that,The treatment regimen of niraparib combined with abiraterone acetate and prednisone indeed achieved this goal, buying precious quality time for patients before their disease progressed to a more drug-resistant stage.This breakthrough highlights the importance for carriers of HRR mutations, particularlyBRCA"The importance of initiating personalized treatment strategies as early as possible for patients with mutated mCSPC."

Niraparib is a highly selective PARP oral inhibitor; abiraterone acetate is an orally administered androgen biosynthesis inhibitor.Prostate cancer is the second most commonly diagnosed malignancy in men globally. Most men are diagnosed with localized prostate cancer, which can be treated with surgery or radiation therapy. Metastatic castration-sensitive prostate cancer, also known as metastatic hormone-sensitive prostate cancer (mHSPC), refers to prostate cancer that still responds to ADT but has spread to other parts of the body. These patients may progress to drug-resistant cancer after continuous ADT.

References:

[1] Johnson & Johnson leads with first PARP inhibitor combo to improve efficacy in patients with HRR-altered mCSPC. Retrieved June 3, 2025 from https://www.investor.jnj.com/news/news-details/2025/Johnson--Johnson-leads-with-first-PARP-inhibitor-combo-to-improve-efficacy-in-patients-with-HRR-altered-mCSPC/default.aspx

Copyright Statement: Individuals are welcome to share this article on their Moments. Unauthorized reproduction by media or organizations in any form to other platforms is prohibited. For authorization, please reply "reprint" on the WeChat Official Account of "WuXi AppTec" to obtain reprint guidelines.