Results of the ARIEL3 study of rucaparib (Rubraca) show promise for the drug’s potential in helping women with advanced ovarian cancer, according to Boulder, Colo.-based Clovis Oncology, a biopharmaceutical company that specializes in cancer treatments.
“Ovarian cancer is the deadliest gynecologic cancer and until very recently, there were limited treatment options for advanced disease,” says David Barley, chief executive officer of the National Ovarian Cancer Coalition. “The potential for targeted therapies that can meaningfully delay recurrence for a large percentage of women with this disease is significant, and we are encouraged by these results from ARIEL3.”
Rucaparib is an oral, small molecule inhibitor of poly (ADP-ribose) polymerase (PARP) 1, 2 and 3, and is in advanced clinical development for the treatment of ovarian cancer.
The phase 3 study of women with platinum-sensitive, high-grade ovarian, fallopian tube or primary peritoneal cancer successfully achieved the primary end point of improved progression-free survival (PFS) by investigator review in each of the three populations studied, the company reports.
PFS was also improved in the rucaparib group compared with placebo by blinded independent central review (BICR), a key secondary end point. Based on these findings, the company plans to submit a supplemental New Drug Application (sNDA) within the next four months for a second-line and later maintenance treatment indication for all women with platinum-sensitive ovarian cancer who have responded to their most recent platinum therapy.
“Based on these encouraging data, it is clear that rucaparib demonstrates a clinically meaningful impact in delaying disease recurrence in women in this trial with advanced ovarian cancer,” says Robert L. Coleman, MD, professor and vice chair, clinical research, in the Department of Gynecologic Oncology and Reproductive Medicine at the University of Texas MD Anderson Cancer Center in Houston, and the U.S. principal investigator for the ARIEL3 study.
“The PFS and safety results achieved in this study are particularly promising because they suggest women are able to stay on rucaparib for a prolonged period of time while gaining benefit. It is also clinically significant that rucaparib not only sustained the most recent response to platinum, but in some patients also enhanced that response, including the elimination of residual tumor.”
ARIEL3 is a double-blind, placebo-controlled, phase 3 trial that enrolled 564 women with platinum-sensitive, high-grade ovarian, fallopian tube or primary peritoneal cancer. The primary efficacy analysis evaluated three prospectively defined molecular subgroups in a step-down manner:
• 1) tumor BRCA-mutant (tBRCAmut) patients, inclusive of germline and somatic mutations of BRCA;
• 2) HRD-positive patients, including BRCA-mutant patients and BRCA wild-type with high loss of heterozygosity, or LOH-high patients;
• 3) the intent-to-treat population, or all patients treated in ARIEL3.
“As has been documented by other agents in this clinical domain, in the ARIEL3 trial, patients carrying a BRCA mutation benefitted to the greatest degree, but efficacy was additionally seen in patients with evidence of non-BRCA-mediated homologous recombination deficiency, and even in patients considered wild-type for both genomic events,” Coleman says. “Further, and importantly, no new safety signals emerged. The availability of rucaparib for patients carrying a BRCA mutation with disease (its current FDA indication) and the anticipated approval as a maintenance therapy critically augments the relatively limited targeted armamentarium for our patients with this devastating illness.”
“I first dosed a patient with rucaparib over five years ago, and these robust and exciting data are consistent with my experience,” says Jonathan Ledermann, professor of medical oncology, director, Cancer Research UK and UCL Cancer Trials Centre, UCL Cancer Institute, and European and ROW Principal Investigator for the ARIEL3 study. “These results show that rucaparib has the potential to provide an enduring and important clinical benefit…irrespective of their tumor genetics.”