FDA Grants Regular Approval to Rubraca for Some With Prostate Cancer

The U.S. Food and Drug Administration has granted regular approval to treatment with Rubraca (rucaparib) for the treatment of adults with a deleterious BRCA mutation (germline and/or somatic)-associated metastatic castration-resistant prostate cancer (mCRPC) that has been previously treated with an androgen receptor-directed therapy.

The approval was announced in a notice issued by the regulatory agency, which also noted that Rubraca was granted accelerated approval for a similar indication in 2020.

The drug’s effectiveness was evaluated in the randomized, open-label TRITON3 clinical trial which was required to confirm the clinical benefit of the 2020 accelerated approval. The trial enrolled 405 patients with mCRPC, of whom 302 had BRCAm and 103 had ATM mutations. Moreover, patients were required to have progressed on a prior androgen receptor pathway inhibitor and could not have received prior chemotherapy in the castration-resistant setting.

Patients received Rubraca or a physician’s choice of an ARPI that they had not previously received, or docetaxel, with the trial’s major efficacy outcome being radiographic progression-free survival (rPFS); overall survival (OS) served as an additional efficacy outcome.

In the trial, Rubraca was associated with what the FDA described as a statistically significant improvement in rPFS compared with treatment consisting of physician’s choice therapy among patients with BRCAm and in the overall population.

Among patients with BRCAm (302 patients), the median rPFS was 11.2 months for Rubraca and 6.4 months for the treatment of physician’s choice. The median OS was 23.2 months and 21.2 months in the respective arms.

“Not only does this provide a potential treatment option for eligible men with earlier stage disease, but it is the first and only PARP inhibitor that has demonstrated superior radiographic (progression-free survival) compared to chemotherapy, which is today the standard of care for these patients,” Patrick J. Mahaffy, the president and CEO of Clovis Oncology, the manufacturer of Rubraca, said in a press release issued in 2022.

The prescribing information for Rubraca, according to the FDA, includes warnings and precautions for myelodysplastic syndrome/acute myeloid leukemia and embryo-fetal toxicity. The recommended dose of the drug is 600 milligrams (mg) in 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.

More about PARP Inhibitors

PARP, or poly ADP-ribose polymerase, is a class of enzymes in the body that are crucial for repairing damaged DNA, as CURE has previously reported. In cancer cells with defective DNA repair mechanisms due to mutations, such as BRCA, PARP inhibitors block the PARP enzyme, preventing the cancer cell from repairing itself. This leads to the cancer cell's death, a concept known as "synthetic lethality."

PARP inhibitors, such as Lynparza (olaparib) and Rubraca, were initially approved as single-agent therapies for the treatment of patients with advanced prostate cancer who had progressed on prior therapies. These approvals were based on studies such as PROFOUND and TRITON, which showed improved progression-free survival and better PSA responses in patients with specific mutations.

Rubraca, as defined by the National Cancer Institute on its website, selectively binds to PARP1, 2 and 3 and inhibits PARP-mediated DNA repair, which enhances the accumulation of DNA strand breaks, promotes genomic instability and induces cell cycle arrest and apoptosis, which in turn may enhance the cytotoxicity of DNA-damaging agents and reverse tumor cell resistance to chemotherapy and radiation therapy.

References

1. 1. FDA grants regular approval to rucaparib for metastatic castration-resistant prostate cancer, by the U.S. FDA. News release; Dec. 17, 2025.
2. 2. FDA Approves Rubraca for Metastatic Castration-Resistant Prostate Cancer That Expresses a BRCA Gene Mutation, by Beth Fand Incollingo. CURE; May 15, 2020. https://www.curetoday.com/view/fda-approves-rubraca-for-metastatic-castrationresistant-prostate-cancer-expresses-brca-gene-mutation
3. 3. Personalizing Prostate Cancer Care With Genetic Testing, PARP Inhibitors, by Kristie L. Kahl. CURE; May 29, 2025.https://www.curetoday.com/view/personalizing-prostate-cancer-care-with-genetic-testing-parp-inhibitors
4. 4. Rucaparib camsylate, by the National Cancer Institute. https://www.cancer.gov/publications/dictionaries/cancer-drug/def/rucaparib-camsylate?redirect=true
5. 5. Rubraca Lengthens Time to Progression in Metastatic Prostate Cancer, by Brielle Benyon. CURE; Oct. 4, 2022. https://www.curetoday.com/view/rubraca-lengthens-time-to-progression-in-metastatic-prostate-cancer

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