On December 17, 2025, the Food and Drug Administration (FDA) approved rucaparib (Rubraca, pharmaand GmbH) for adults with a deleterious BRCA mutation (BRCAm) (germline and/or somatic)-associated metastatic castration-resistant prostate cancer (mCRPC) previously treated with an androgen receptor-directed therapy. Patients should be selected for therapy using an FDA-approved companion diagnostic (CDx). Rucaparib was granted accelerated approval in 2020 for a similar indication.

Full prescribing information for Rubraca will be posted on Drugs@FDA.

Safety and Efficacy

Efficacy was evaluated in TRITON3 (NCT02975934), a randomized, open-label trial required to confirm the clinical benefit of the 2020 accelerated approval. TRITON3 enrolled 405 patients with mCRPC, of whom 302 had BRCAm and 103 had ATM mutations (ATMm). Patients were required to have progressed on a prior androgen receptor pathway inhibitor (ARPI) and could not have received prior chemotherapy in the castration-resistant setting.

Patients were randomized (2:1) to receive either rucaparib or physician’s choice of an ARPI they had not previously received (enzalutamide or abiraterone acetate) or docetaxel. Randomization was stratified by performance status, presence of hepatic metastases, and type of mutation (BRCA1m, BRCA2m, or ATMm). Patients maintained a castrate level of testosterone via treatment with androgen deprivation therapy or prior surgical castration.

The major efficacy outcome was radiographic progression-free survival (rPFS) assessed by independent radiology review in patients with BRCAm and in the overall population. Overall survival (OS) was an additional efficacy outcome.

Rucaparib demonstrated a statistically significant improvement in rPFS compared to treatment of physician’s choice in patients with BRCAm and in the overall population. In patients with BRCAm (n = 302), median rPFS was 11.2 months (95% CI: 9.2, 13.8) for rucaparib and 6.4 (95% CI: 5.4, 8.3) for treatment of physician’s choice (hazard ratio [HR] 0.50 [95% CI: 0.36, 0.69]); p-value <0.0001). Median OS was 23.2 months (95% CI: 19.1, 25.2) and 21.2 months (95% CI: 18.0, 23.1) in the respective arms (HR 0.91 [95% CI: 0.68, 1.20]); p-value not significant). In an exploratory analysis in the 103 (25%) patients with ATMm, the rPFS HR was 0.95 (95% CI: 0.59, 1.52) and the OS HR was 1.21 (95% CI: 0.77, 1.90), indicating that the overall improvement was primarily attributed to the results seen in patients with BRCAm.

The prescribing information includes warnings and precautions for myelodysplastic syndrome/acute myeloid leukemia and embryo-fetal toxicity.

The recommended rucaparib dose is 600 mg (two 300 mg tablets) taken orally twice daily with or without food, for a total daily dose of 1,200 mg until disease progression or unacceptable toxicity.

Expedited Programs

This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment. The FDA approved this application 1 month ahead of the FDA goal date.

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 1-800-FDA-1088.

For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact OCE’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov.

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