General Information

Rubraca (rucaparib) is a poly (ADP-ribose) polymerase (PARP) inhibitor.

Rubraca is specifically indicated as monotherapy for the treatment of patients with deleterious BRCA mutation (germline and/or somatic) associated advanced ovarian cancer who have been treated with two or more chemotherapies. Patients should be selected for therapy based on an FDA-approved companion diagnostic for Rubraca. Rubraca is also indicated as a maintenance treatment for adults with ovarian cancer, fallopian tube cancer, or primary peritoneal cancer whose cancer has come back and who are in response (complete or partial response) to a platinum-based chemotherapy.

Rubraca is specifically indicated for adult patients with a deleterious BRCA mutation (germline and/or somatic)-associated metastatic castration-resistant prostate cancer (mCRPC) who have been treated with androgen receptor-directed therapy and a taxane-based chemotherapy.

Rubraca is supplied as a tablet for oral administration. The recommended dose is 600 mg orally twice daily with or without food. Treatment should be continued until disease progression or unacceptable toxicity.

Clinical Results

FDA Approval

Rubraca has been approved under accelerated approval based on objective response rate and duration of response. Continued approval may be contingent upon verification and description of clinical benefit in confirmatory trials.

The accelerated approval of Rubraca for ovarian cancer for was based on two multicenter, single-arm, open-label clinical trials, Study 1 and Study 2, in 106 patients with advanced BRCA-mutant ovarian cancer who had progressed after 2 or more prior chemotherapies. All 106 patients received Rubraca 600 mg orally twice daily as monotherapy until disease progression or unacceptable toxicity. Objective response rate (ORR) and duration of response (DOR) were assessed by the investigator and independent radiology review (IRR) according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. The Objective Response Rate was 54%, with a Complete Response of 9%, Partial Response of 45% and Median DOR of 9.2 months. Response assessment by independent radiology review was 42%, with a median DOR of 6.7 months. Investigator-assessed ORR was 66% in platinum-sensitive patients, 25% in platinum-resistant patients, and 0% in platinum-refractory patients. ORR was similar for patients with a BRCA1 gene mutation or BRCA2 gene mutation.

The FDA approval of Rubraca for prostate cancer was based on objective response rate (ORR) and duration of response (DOR) data from the multi-center, single arm TRITON2 clinical trial. The major efficacy outcomes are confirmed ORR and DOR by modified RECIST version 1.1/PCWG3 criteria assessed by blinded independent radiologic review (IRR). Confirmed prostate-specific antigen (PSA) response rate is an additional prespecified endpoint. Data showed a 44% ORR (N=62) by blinded-IRR assessment. Objective response rates were similar for patients with a germline BRCA versus somatic BRCA mutation. Median DOR by blinded-IRR assessment was not evaluable (NE) at data cut-off. Additionally, a 55% confirmed prostate specific antigen (PSA) response rate was observed in an analysis of 115 patients with a deleterious BRCA mutation (germline and/or somatic) and measurable or non-measurable disease.

Mechanism of Action

Rubraca (rucaparib) is a poly (ADP-ribose) polymerase (PARP) inhibitor; PARP's play a role in DNA repair. In vitro studies have shown that rucaparib-induced cytotoxicity may involve inhibition of PARP enzymatic activity and increased formation of PARP-DNA complexes resulting in DNA damage, apoptosis, and cell death. Increased rucaparib-induced cytotoxicity was observed in tumor cell lines with deficiencies in BRCA1/2 and other DNA repair genes. Rucaparib has been shown to decrease tumor growth in mouse xenograft models of human cancer with or without deficiencies in BRCA.