ALAMEDA, Calif.—Exelixis Inc. announced today that it is initiating COSMIC-313, a Phase 3 pivotal trial of cabozantinib (Cabometyx) in combination with nivolumab and ipilimumab, versus nivolumab and ipilimumab, in patients with previously untreated advanced renal cell carcinoma (RCC) with intermediate- or poor-risk disease per the International Metastatic Renal Cell Carcinoma Database Consortium. The primary endpoint of the trial is progression-free survival, and the secondary endpoints are overall survival and objective response rate.
“Clinical observations suggest cabozantinib promotes an immune-permissive environment, which could present an opportunity for additive or synergistic effects with immune checkpoint inhibitors,” said Gisela Schwab, M.D., president, Product Development and Medical Affairs and chief medical officer, Exelixis. “The mechanisms of action of single agent cabozantinib and the combination of nivolumab and ipilimumab are complementary, and each has demonstrated efficacy in advanced renal cell carcinoma. The further combination of these agents as a triplet regimen may offer promise to previously untreated patients with intermediate- or poor-risk disease, who are known to have poor treatment outcomes.”
COSMIC-313 is a multicenter, randomized, double-blinded, controlled Phase 3 pivotal trial that aims to enroll approximately 676 patients at 150 sites globally. Patients will be randomized 1:1 to the experimental arm of cabozantinib in combination with nivolumab and ipilimumab, and to the control arm of nivolumab and ipilimumab in combination with matched placebo. Bristol-Myers Squibb is providing nivolumab and ipilimumab for use in the trial.
The design of this trial was informed by results from the ongoing Phase 1b study of cabozantinib plus nivolumab with or without ipilimumab in patients with previously treated advanced genitourinary cancers, including RCC. The Phase 1b trial is being conducted by the U.S. National Cancer Institute, and includes centers from its Experimental Therapeutics Clinical Trials Network.
COSMIC-313 is the third Phase 3 pivotal trial to investigate cabozantinib in combination with immune checkpoint inhibitors. In December 2018, Exelixis and its partner Ipsen also announced the initiation of COSMIC-312, a Phase 3 pivotal trial of cabozantinib in combination with atezolizumab versus sorafenib in previously untreated advanced HCC. The trial will also explore single-agent activity of cabozantinib in the first-line setting.
Not long ago in January, Exelixis announced that the Food and Drug Administration (FDA) approved cabozantinib tablets for patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib. HCC is the most common form of liver cancer and the fastest-rising cause of cancer-related death in the U.S.
“This new indication for Cabometyx is an important treatment advance for patients with this aggressive form of liver cancer, a community in need of new therapeutic options. This approval is an important milestone as we continue to explore how Cabometyx may benefit people with difficult-to-treat-cancers beyond renal cell carcinoma. We would like to thank the patients and clinicians who participated in CELESTIAL and to acknowledge the team at the FDA for their continued collaboration during the review of our application,” noted Michael M. Morrissey, Ph.D., president and chief executive officer of Exelixis, in a press release.
The FDA’s approval of Cabometyx was based on results from the CELESTIAL Phase 3 pivotal trial of Cabometyx for patients with advanced HCC who received prior sorafenib. Cabometyx demonstrated a statistically significant and clinically meaningful improvement in overall survival (OS) versus placebo.
In the U.S., Cabometyx is currently approved for the treatment of patients with advanced RCC, and for the treatment of patients with HCC who have been previously treated with sorafenib. Cabometyx has also received regulatory approvals in the European Union and additional countries and regions worldwide.