Phase II data included in NDA for rucaparib in ovarian cancer presented at European Society for Medical Oncology Congress- Clovis Oncology

The FDA has set Clovis Oncology a review date of 23 February 2017 for rucaparib which is currently under priority review as a monotherapy for ovarian cancer patients with BRCA-mutated tumors who have received two or more chemotherapies. The application is based on data from a pair of open-label, single-arm Phase II studies Study 10 (NCT01482715) and ARIEL2 (NCT01891344) .

The objective response rate (ORR), which includes complete and partial responses in the efficacy population was 57/106, or 54%, including nine (9%) complete responders and 48 (45%) partial responders. Thirty-six patients (34%) had stable disease as the best response, while nine patients (9%) had progressive disease as the best response and four (4%) were not evaluable. For the 42 patients from Study 10 included in the efficacy population, the ORR was 25/42, or 60%. For the 64 patients from ARIEL2 included in the efficacy population, the ORR was 32/64, or 50%. Study 10 was limited to platinum sensitive patients; ARIEL2 included platinum sensitive, platinum resistant and platinum refractory patients. In addition, ORR was assessed by subgroups including BRCA mutation type, number of prior chemotherapies and prior platinum regimens, PFI and platinum status. Patients with a BRCA1 (n=67) or BRCA2 (n=39) mutation both showed an ORR of 54% in line with the overall population.

Additionally, analyses not contained within the NDA submission showed median progression-free survival by investigator assessment in the efficacy population to be 10.0 months. Of note, 79% of patients remained progression-free at six months, and 41% remained progression-free at 12 months. Of the 377 ovarian cancer patients treated with a starting dose of rucaparib 600 mg, 377 (100%) experienced a treatment-emergent adverse event (AE) of any grade, and 229 (61%) experienced a treatment-emergent AE grade 3 or higher. Treatment-related AEs leading to dose reduction occurred in 167 patients (44%), and treatment discontinuation in 30 patients (8%). The primary reasons for dose reduction were anemia/decreased hemoglobin (17%), asthenia/fatigue (14%) and nausea (11%). Details of the data on which the application is based were presented at the European Society for Medical Oncology Congress.

Comment: If the FDA review is successful, rucaparib will be the second PARP inhibitor approved by the FDA after AstraZeneca�s Lynparza (olaparib) which is approved for advanced ovarian cancer associated with defective BRCA genes. Rucaparib is also being investigated in two Phase III trials, one for ovarian cancer maintenance after chemo and the second comparing it as a monotherapy to standard chemo.