Clovis to Apply for Expanded FDA Approval for Rubraca in Ovarian Cancer Patients

Clovis to Apply for Expanded FDA Approval for Rubraca in Ovarian Cancer Patients

Clovis Oncology plans to apply to the U.S. Food and Drug Administration (FDA) for expanded approval of Rubraca (rucaparib) as a second-line and later maintenance treatment for all women with ovarian cancer who have responded to their latest treatment with platinum chemotherapy.

The decision came with the company’s announcement of positive outcomes of a Phase 3 trial (NCT01968213) called ARIEL3. The study showed Rubraca improved progression-free survival in all patients regardless of the type of tumor mutations — which allowed the trial to meet its primary goal.

“We are very pleased with these positive ARIEL3 topline results that strongly demonstrate the potential of rucaparib [Rubraca] to help women with platinum-sensitive, advanced ovarian cancer,” Patrick J. Mahaffy, president and CEO of Clovis Oncology, said in a press release.

The study included women with ovarian cancer having mutations in the BRCA genes and patients who were homologous recombination deficiency (HRD)-positive, including patients with and without BRCA mutations. All women had been treated with, and responded to, platinum-based therapy before being randomized to receive either Rubraca or placebo in the trial.

Analyses showed Rubraca improved progression-free survival in all patient groups. The findings were confirmed by a blinded, independent central review — an analysis that made up one of the trial’s secondary goals.

“These results reinforce the potentially foundational role of rucaparib in the management of advanced ovarian cancer, as demonstrated by both investigator review and the blinded independent central review,” Mahaffy said.

The 196 women with BRCA mutations saw the greatest benefits of the treatment, with investigator’s analysis showing a progression-free survival of 16.6 months. The independent review judged the progression-free survival to be even longer — 26.8 months. In comparison, placebo-treated patients survived without tumor progression for 5.4 months.

Among 354 women with HRD-positive tumors, survival without progression was 13.6 months, according to investigators, and 22.9 months, according to the review committee. Those in the placebo group lived for roughly five months.

An analysis including the entire group of patients in the trial suggested a progression-free survival of 10.8 months, or 13.7 months by independent review.

HRD-positive and negative patients who had no BRCA mutations also benefited from the treatment, although less so compared to those with mutated BRCA genes.

In addition, patients who had measurable tumors when entering the study saw a further reduction of their tumors when treated with Rubraca, with a substantial proportion of patients having complete responses.

“Most importantly, we are grateful to the patients, caregivers, and investigators who participated in this study,” Mahaffy said. “We look forward to sharing these data in greater detail at a medical meeting later this year and submitting our sNDA [supplemental New Drug Application] as rapidly as possible, with the ultimate goal of making rucaparib available to more women battling ovarian cancer.”

The company announced that its intention is to have the sNDA ready within four months.

The study’s principal investigator, Dr. Robert L. Coleman, spoke of the data as having a “clinically meaningful impact” in terms of delaying cancer recurrence in women with advanced disease.

Rubraca’s safety in the trial was in line with what had been observed in earlier trials of the drug, with no new side effects in addition to those mentioned in the drug’s prescription label.

“The PFS [progression-free survival] 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,” said Coleman, who is also a professor and vice chair of clinical research in the Department of Gynecologic Oncology and Reproductive Medicine at the University of Texas MD Anderson Cancer Center.

“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,” Coleman added.

Rubraca was approved by the FDA in December 2016 for the treatment of advanced ovarian cancer in patients with BRCA mutations. The drug acts as a PARP-inhibitor, interfering with a DNA repair pathway that people carrying BRCA mutations particularly depend on.

“I first dosed a patient with rucaparib over five years ago, and these robust and exciting data are consistent with my experience,” said Jonathan Ledermann, a professor of medical oncology and the European and Rest of World Principal Investigator for the ARIEL3 study.

“These results show that rucaparib has the potential to provide an enduring and important clinical benefit in women with advanced ovarian cancer, irrespective of their tumor genetics. This is a very important step forward for women with advanced ovarian cancer,” added Ledermann, who is also director of Cancer Research UK and University College London (UCL) Cancer Trials Centre at the UCL Cancer Institute.