On September 13, 2017 Clovis Oncology, Inc. (NASDAQ: CLVS) reported that comprehensive data from the Phase 3 ARIEL3 study of rucaparib for maintenance treatment of advanced ovarian cancer were published online today in The Lancet (Press release, Clovis Oncology, SEP 13, 2017, View Source [SID1234520503]). The ARIEL3 study successfully achieved its primary and key secondary endpoints – improved progression-free survival (PFS) by both investigator review and blinded independent central review (BICR), respectively – in each of the three populations studied, as well as its exploratory endpoints.
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ARIEL3 is a double-blind, placebo-controlled, phase 3 trial of rucaparib 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 sub-groups in a step-down manner: 1) tumor BRCA mutant (tBRCAmut) patients, inclusive of germline and somatic mutations of BRCA (n=196); 2) HRD patients, including BRCA-mutant patients and BRCA wild-type with high loss of heterozygosity, or LOH-high patients (n=354), and, finally, 3) the intent-to-treat population, or all patients treated in ARIEL3 (n=564). The study achieved its primary endpoint of improved PFS by investigator review in each of three populations. PFS was also improved in the rucaparib group compared with placebo by BICR, a key secondary endpoint, in all three populations. In addition, rucaparib improved objective response rate vs placebo among evaluable trial participants in all three study populations.
"The publication of the ARIEL3 data in this prestigious, peer-review journal reinforces the importance of identifying new therapies that provide meaningful clinical benefit to women with advanced ovarian cancer, and speaks to the high quality of the study design and the data we were able to deliver," said Patrick J. Mahaffy, President and CEO of Clovis Oncology. "We extend our sincere thanks to the study investigators and authors, as well as the many patients, who supported and participated in ARIEL3."
"The extension in PFS in the ARIEL3 intent-to-treat population demonstrates that patients with platinum-sensitive ovarian carcinoma can derive robust clinical benefit from rucaparib maintenance treatment, regardless of their mutational status," said Robert L. Coleman, M.D., professor and vice chair, clinical research, in the Department of Gynecologic Oncology and Reproductive Medicine at The University of Texas MD Anderson Cancer Center and the U.S. principal investigator for the ARIEL3 study. "Additionally, the ARIEL3 study was intentionally designed to deliver multiple, key insights that will help inform treatment decisions and management of advanced ovarian cancer patients going forward."
According to the paper published today, treatment emergent adverse events (TEAEs) in the ARIEL3 rucaparib group were generally managed with dose modifications and not associated with increased mortality or morbidity compared with the placebo group. Safety data from ARIEL3 demonstrate consistency with prior rucaparib studies.
In December 2016, Rubraca became the first PARP inhibitor approved by the U.S. Food and Drug Administration (FDA) as monotherapy for treatment of patients with deleterious BRCA mutation (germline and/or somatic) associated advanced ovarian cancer who have been treated with two or more prior chemotherapies. During the fourth quarter of 2016, a Marketing Authorization Application (MAA) was submitted and accepted in Europe for Rubraca in the same ovarian cancer-treatment indication.
Based on the ARIEL3 findings, Clovis Oncology plans to submit a supplemental New Drug Application (sNDA) to the U.S. FDA for a second line or later maintenance treatment indication in ovarian cancer by the end of October 2017. In early 2018, the Company plans to file an MAA in Europe for the maintenance treatment indication upon receipt of a potential approval for the treatment indication.
About the ARIEL3 Clinical Trial
The ARIEL3 pivotal study of rucaparib is a confirmatory randomized, double-blind study comparing the effects of rucaparib against placebo to evaluate whether rucaparib given as a maintenance treatment to platinum-sensitive ovarian cancer patients can extend the period of time for which the disease is controlled after a complete or partial response to platinum-based chemotherapy. The study enrolled 564 patients with high-grade epithelial ovarian, fallopian tube or primary peritoneal cancer. To be eligible for the study, participants had to have received at least two prior platinum-based treatment regimens, been sensitive to the penultimate platinum regimen, and achieved a complete or partial response to their most recent platinum-based regimen. There were no genomic selection criteria for this study. Trial participants were randomized 2:1 to receive 600 milligrams of rucaparib twice daily (BID) or placebo.
About Rucaparib
Rucaparib is an oral, small molecule inhibitor of PARP1, PARP2 and PARP3 being developed in ovarian cancer as well as several additional solid tumor indications. In December 2016, rucaparib became the first PARP inhibitor approved by the U.S. Food and Drug Administration (FDA) as monotherapy for treatment of patients with deleterious BRCA mutation (germline and/or somatic) associated advanced ovarian cancer who have been treated with two or more prior chemotherapies. Studies open for enrollment or under consideration include ovarian, prostate, breast, pancreatic, gastroesophageal, bladder, lung and urothelial cancers. Clovis is also developing rucaparib in patients with mutant BRCA tumors and other DNA repair deficiencies beyond BRCA – commonly referred to as homologous recombination deficiencies, or HRD. Clovis holds worldwide rights for rucaparib.
About Ovarian Cancer
Ovarian cancer is the sixth deadliest cancer amongst women in Europe,i where more than 65,000 women are diagnosed annually.ii Ovarian cancer is challenging to treat, and most women will relapse after surgery and chemotherapy. The 80 to 85 percent of women diagnosed in the later stages of the disease (III and IV) have particularly poor outcomes.iii Approximately one in four women with ovarian cancer have a germline or somatic BRCA mutation,iv and new treatment options are needed to treat unique patient populations.