The U.S. Food and Drug Administration (FDA) has granted priority review to Clovis Oncology’s application seeking approval of Rubraca (rucaparib) for treating men with recurrent metastatic castration-resistant prostate cancer (mCRPC) and BRCA mutations.
The priority review status will shorten Rubraca’s regulatory review for this indication to six months from the standard 10 months. Clovis submitted the application to the FDA in November 2019, and the agency has set a Prescription Drug User Fee Act action date for May 15 this year, meaning that a decision is due by then.
“We are encouraged by the FDA’s decision to grant priority review to the Rubraca application, which focuses on eligible patients with advanced prostate cancer, for whom new treatment options are very much needed,” Patrick J. Mahaffy, Clovis Oncology’s president and CEO, said in a press release.
Nearly 12% of men with mCRPC have a mutation in the BRCA1 or BRCA2 genes, which are involved in DNA repair. These tumors rely on other DNA repair mechanisms — including those involving PARP enzymes that act as DNA damage sensors — to survive and grow.
Thus, treatments that block PARPs’ activity (PARP inhibitors), such as Rubraca, are particularly effective in BRCA-mutated tumors. Rubraca is already approved for the treatment of several gynecologic tumors carrying BRCA mutations, and as a maintenance therapy regardless of BRCA mutations.
Rubraca’s new application was supported by data from the TRITON2 Phase 2 trial (NCT02952534), which is evaluating its safety and effectiveness in up to 360 mCRPC patients with mutations in BRCA genes or in other 13 DNA repair genes known to increase susceptibility to PARP inhibitors.
Besides eligible mutations, participants must have experienced disease progression after at least one but no more than two previous androgen-receptor targeted therapies and one prior taxane-based chemotherapy for their castration-resistant disease.
TRITON2’s main goals were to assess overall response rates in men with measurable disease, and the proportion of men who saw a reduction in the levels of prostate-specific antigen (PSA) — a biomarker of prostate cancer — after treatment.
Secondary goals included duration of response, time to disease progression or death, overall survival, and safety measures.
Early positive data from TRITON2 led to Rubraca’s breakthrough therapy designation by the FDA for the treatment for mCRPC patients with BRCA mutations, a status intended to accelerate the therapy’s development and review.
Updated data was presented at the European Society for Medical Oncology Congress 2019 in September. As of Feb. 28 last year, 190 patients (98 with a BRCA mutation) had received Rubraca, with a median follow-up of 13.1 months.
Among patients with BRCA mutations, results showed that 43.9% of those with measurable disease responded to treatment, and that 60% of these responses lasted at least 24 weeks. Also, 52% of patients had a confirmed PSA response (deemed as a 50% or greater reduction in PSA levels), which lasted a median of 5.5 months.
Rubraca’s safety profile was consistent with prior reports from TRITON2 and other trials, with the most common adverse events being fatigue (55.3%), nausea (49.5%), anemia (37.9%), decreased appetite (27.9%), transient increase in liver enzymes (24.7%), constipation (24.7%), vomiting (22.1%), and diarrhea (21.1%).
“Recently presented data suggests that Rubraca may play a meaningful role in the treatment of patients with BRCA1/2-mutant recurrent, metastatic castrate-resistant prostate cancer, and this filing represents an important milestone for Clovis as it brings us one step closer to potentially making this valuable therapy available,” Mahaffy said.
Clovis Oncology is also evaluating whether Rubraca is superior to physician’s choice of therapy in men with advanced prostate cancer and mutations in BRCA and ATM genes in the international TRITON3 Phase 3 study (NCT02975934). The trial is still enrolling; more information on recruitment locations can be found here.