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 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 for this indication was approved under accelerated approval based on objective response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

The accelerated approval of Rubraca 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.

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.