Clovis Oncology (NASDAQ:CLVS) announced today the oral presentation of the primary efficacy and safety data from its NDA dataset for rucaparib at the 2016 ESMO Congress inCopenhagen. Rucaparib is currently under priority review with FDA for the monotherapy treatment of advanced ovarian cancer in patients with BRCA-mutated tumors inclusive of both germline and somatic BRCA mutations who have been treated with two or more chemotherapies, and the submission has a PDUFA date of February 23, 2017.
Rucaparib is the Company’s oral, small molecule inhibitor of PARP1, PARP2 and PARP3 currently being developed for the treatment of ovarian cancer, specifically in patients with tumors with BRCA mutations and other DNA repair deficiencies beyond BRCA, including those with high genomic loss of heterozygosity (LOH) also known as “BRCA-like.” The current NDA submission seeks approval in patients with tumor BRCA mutations, which includes both germline and somatic mutations.
“These results demonstrate that rucaparib may represent an important option for women with multiply relapsed BRCA-mutated ovarian cancer based on its encouraging efficacy and tolerability,” said Rebecca S. Kristeleit, MD, PhD, The University College London, Cancer Institute, London, UK. “In my opinion, rucaparib has the hallmarks of an important new therapeutic option for ovarian cancer patients.”
“We are pleased to present the primary efficacy and safety dataset that has been submitted to the FDA as the basis of our NDA for rucaparib in the treatment of advanced ovarian cancer. If approved, rucaparib would be the first PARP inhibitor in the U.S. indicated to treat ovarian cancer patients with germline or somatic BRCA mutations who have received two prior chemotherapies. Women with BRCA mutations represent about 25% of patients in the US living with ovarian cancer,” said Patrick J. Mahaffy, CEO and President of Clovis Oncology. “Our NDA review is ongoing with FDA, and in addition we are actively preparing for a European submission during the fourth quarter of 2016.”
Data from subgroups of two multicenter, single-arm open-label phase 2 studies, Study 10 (NCT01482715) and ARIEL2 (NCT01891344) were combined for an integrated efficacy and safety analysis which further characterized the clinical benefit of rucaparib at the recommended starting dose of 600 mg BID in women with advanced ovarian cancer. In the two studies, 377 patients met the criteria for inclusion in the safety population (diagnosis of ovarian cancer and having received one or more doses of the recommended dose of 600 mg of rucaparib), and 106 patients met the criteria for inclusion in the efficacy population (received 2 or more prior chemotherapies, including 2 or more platinum-based regimens, had a mutation of BRCA (germline or somatic), and received one or more doses of the recommended dose of 600 mg of rucaparib.
The major efficacy outcome measure for this analysis was objective response rate (ORR) and duration of response (DOR) as assessed by the investigator according to RECIST. All responses were confirmed.
For the efficacy population (n=106), the median number of prior chemotherapies was three, with 39% having received two prior therapies and 61% of patients having received three or more prior therapies. The median number of prior platinum-based therapies was two, with 57% having received two prior platinum-based therapies, and 43% having received three or more prior platinum-based therapies. Seventy-five percent of patients in the efficacy population were platinum-sensitive (as defined by recurrence after progression free interval (PFI) of ≥6 months), 19% were platinum resistant (recurrence after PFI <6 months) and 7% were platinum refractory (progression on platinum, PFI <2 months).