Clovis Oncology’s Rubraca® (rucaparib) Met the Primary Endpoint of Significantly Improving Progression-Free Survival vs. Chemotherapy in the ARIEL4 Randomized Phase 3 Treatment Study in Later-line Ovarian Cancer Patients with a BRCA mutation

Clovis Oncology, Inc. (NASDAQ: CLVS), today announced topline data from the randomized Phase 3 ARIEL4 study of Rubraca, which met its primary endpoint of improved investigator-assessed progression-free survival (InvPFS) compared to chemotherapy in relapsed ovarian cancer patients with a tumor mutation of BRCA who have received two or more prior lines of chemotherapy.

“We are pleased with these topline results from the ARIEL4 trial, which confirm the clinical benefit of Rubraca versus chemotherapy, including platinum-based chemotherapy, as a treatment for women with BRCA mutation-positive advanced ovarian cancer, including patients who are platinum-resistant,” said Patrick J. Mahaffy, President and CEO of Clovis Oncology. “We look forward to sharing comprehensive results at an upcoming medical meeting.”

The ARIEL4 study (NCT02855944) is a Phase 3 multicenter, randomized study evaluating Rubraca versus chemotherapy in platinum-sensitive, partially platinum-sensitive and platinum-resistant patients with relapsed ovarian cancer and a BRCA mutation (inclusive of germline and/or somatic) who have received two or more prior lines of chemotherapy. The primary endpoint of the study is InvPFS, with a step down analysis from the efficacy population (if significant) to the ITT population. The efficacy population comprised the group of patients with a deleterious tumor BRCA mutation and excluded those with a BRCA reversion mutation as determined by a blood test developed by Guardant Health. Development of reversion mutations that restore BRCA protein function are associated with resistance to platinum-based chemotherapies and PARP inhibitors in BRCA-mutant cancers, and these occur more frequently in platinum-resistant vs platinum-sensitive patients (13% and 2% respectively in the ARIEL2 study).ⁱ

Completion of ARIEL4 is a post-marketing commitment in the U.S. and EU.

349 women were enrolled in North and South America, Europe and Israel. The efficacy population (n=325) comprised the group of patients with a deleterious tumor BRCA mutation and excluded those with a BRCA reversion mutation. The rucaparib arm (n=220) successfully achieved statistical significance over the chemotherapy arm (n=105) for the primary endpoint of InvPFS with a hazard ratio of 0.639 (p=0.0010). The median PFS for the patients in the efficacy population treated with rucaparib was 7.4 months vs. 5.7 months among those who received chemotherapy.

In addition, in the ITT population (n=349), the rucaparib arm (n=233) successfully achieved statistical significance over the chemotherapy arm (n=116) for the primary endpoint of InvPFS with a hazard ratio of 0.665 (p=0.0017). The median PFS for the patients in the ITT population treated with rucaparib was 7.4 months vs. 5.7 months among those who received chemotherapy.

Patients with a BRCA reversion mutation represented 7 percent of patients enrolled in the study and as anticipated, InvPFS results for those patients showed limited benefit from Rubraca therapy.

An interim analysis of overall survival, a secondary endpoint in the study in which 51 percent of events have occurred in the ITT population, showed a trend toward an overall survival (OS) advantage in the chemotherapy arm, but was confounded by the high rate (64%) of per-protocol crossover to Rubraca following progression on chemotherapy. Importantly, an analysis of the ITT population of patients showed a trend toward an OS advantage for those patients who received Rubraca at any point in the trial versus those who did not.

Adverse events were consistent with the known safety profiles of Rubraca and chemotherapy.

The most common (>5%) treatment-emergent grade 3/4 adverse events (TEAEs) among all patients treated with rucaparib (n=232) in the ARIEL4 study were anemia/decreased hemoglobin (22%), neutropenia/decreased absolute neutrophil count (10%), asthenia/fatigue (8%), thrombocytopenia/decreased platelets (8%), and increased ALT/AST (8%).

“The ARIEL4 study verified that women with relapsed, BRCA mutation-positive advanced ovarian cancer, including those who are platinum-sensitive or -resistant, received benefit with rucaparib treatment when compared to chemotherapy,” said Dr. Amit Oza, Head of the Division of Medical Oncology & Hematology, Medical Director of the Cancer Clinical Research Unit at Princess Margaret (PM) Cancer Centre, co-Director of the Drug Development Program at PM Cancer Centre, Senior Scientist at the Princess Margaret Cancer Centre, and Professor of Medicine at University of Toronto. “These results underscore the importance of rucaparib as a treatment option for women with BRCA-mutant advanced ovarian cancer.”

Ovarian cancer ranks fifth in cancer deaths among women in the U.S.ⁱⁱ and EUⁱⁱⁱ. While there are a growing number of therapies to treat ovarian cancer, after initial therapy, 70-90% of U.S. women^iv with advanced diseas