Priority review has been granted by the FDA for a new drug application (NDA) for rucaparib as a treatment for patients with <em>BRCA</em>-positive advanced ovarian cancer who have received at least 2 prior lines of chemotherapy, according to Clovis, the manufacturer of the PARP inhibitor.
Robert L. Coleman, MD
Robert L. Coleman, MD
Priority review has been granted by the FDA for a new drug application (NDA) for rucaparib as a treatment for patients withBRCA-positive advanced ovarian cancer who have received at least 2 prior lines of chemotherapy, according to Clovis, the manufacturer of the PARP inhibitor.
The application is based on data from 106 patients across 2 trials, including the ARIEL2 study. In a pooled analysis of data from the studies, the objective response rate (ORR) was 54% (95% CI, 44-64) with rucaparib.
Rucaparib previously received a breakthrough therapy designation from the FDA in this setting in April 2015. The FDA is scheduled to make a final decision on the application for the PARP inhibitor by February 23, 2017, as part of the Prescription Drug User Fee Act.
“Recurrent ovarian cancer remains a very difficult disease to treat, even among women who carry, or whose tumors have a mutation in theBRCAgenes. Despite the available treatment options, few effective therapies are at our disposal. Thus, the opportunity to treat women with germline or somatic BRCAmutations with rucaparib after 2 prior lines of platinum-based therapy, represents a meaningful step forward for our patients,” Robert L. Coleman, MD, professor and deputy chairman, vice chair, clinical research, Ann Rife Cox Chair in Gynecology, department of Gynecologic Oncology and reproductive medicine at University of Texas MD Anderson Cancer Center and one of the principal investigators in the ARIEL clinical trial program, said in a statement.
The 106 patients comprised 42 patients from a phase I/II study (NCT01482715) and 64 patients from the ARIEL2 phase II study (NCT01891344). Both trials were multicenter, single-arm, open-label studies in patients withBRCA-positive ovarian cancer who had progressed on 2 or more prior chemotherapies.
The phase I/II trial included only platinum-sensitive patients, while ARIEL2 enrolled patients who were platinum sensitive, resistant, or refractory. The group of 106 patients had a median number of prior therapies of 3 and a median age of 59 years.
The starting does of rucaparib for all patients was 600 mg twice daily. The primary outcome measures for both studies was investigator-assessed ORR and duration of response (DOR) per RECIST version 1.1.
In the pooled analysis of the 2 trials, the complete response (CR) rate was 9% and the partial response (PR) rate was 45%. The median DOR was 9.2 months (95% CI, 6.6-11.6). ORR rates were similar, regardless of whether patients had germline or somaticBRCAmutations, or mutations of the BRCA1gene versus the BRCA2gene. Progressive disease occurred in 9 of the 106 patients.
Among the 42 patients in the phase I/II study, the ORR was 60% (95% CI, 43-74), which included a CR rate of 10% and a PR rate of 50%. The median DOR was 7.8 months (95% CI, 5.6-10.5).
In the ARIEL2 trial, the ORR was 50% (95% CI, 37-63), comprising a CR rate of 8% and a PR rate of 42%. The median DOR was 11.6 months (95% CI, 5.5-18.2).
The safety analysis for rucaparib included 377 patients from the 2 studies who received rucaparib at 600 mg twice daily. The most common grade 3/4 adverse events (AEs) were anemia/decreased or low hemoglobin (25%), fatigue/asthenia (11%), and increased ALT/AST (11%).
Clovis reported in a press release that the elevated AST and ALT levels were asymptomatic, reversible, and were mostly not linked to increases in bilirubin. The company further noted that the raised levels returned to normal with continued rucaparib therapy.
Eight percent of patients discontinued treatment due to AEs associated with rucaparib. There was 1 case of myelodysplastic syndrome.
“The acceptance of the rucaparib NDA submission represents an important milestone for rucaparib, and for Clovis,” Patrick J. Mahaffy, president and CEO of Clovis Oncology, said in a statement. “There is tremendous need for additional therapeutic options for patients with advanced mutantBRCAovarian cancer and we look forward to cooperating with FDA on the rucaparib NDA review.”