On October 16, Exelixis announced that its global phase III CELESTIAL trial met its primary endpoint of overall survival, with cabozantinib (Cabometyx) providing a statistically significant and clinically meaningful improvement in median overall survival compared to placebo in patients with advanced hepatocellular carcinoma (HCC). The independent data monitoring committee for the study recommended that the trial should be stopped for efficacy following review of the second planned interim analysis.
CELESTIAL is a randomized, global phase III trial of cabozantinib vs placebo in patients with advanced HCC who have been previously treated with sorafenib. The safety data in the study were consistent with the established profile of cabozantinib. Based on these results, Exelixis plans to submit a supplemental New Drug Application (sNDA) to the U.S. Food and Drug Administration (FDA) in the first quarter of 2018. Detailed results from CELESTIAL will be submitted for presentation at a future medical conference.
“We are excited that these positive results from the phase III CELESTIAL trial bring us one step closer to the potential of offering previously treated patients with this aggressive form of advanced liver cancer a much-needed new treatment option,” said Gisela Schwab, MD, President, Product Development and Medical Affairs and Chief Medical Officer, Exelixis.
In March 2017, the FDA granted orphan drug designation to cabozantinib for the treatment of advanced HCC.
More About the CELESTIAL Study
CELESTIAL is a randomized, double-blind, placebo-controlled study of cabozantinib in patients with advanced HCC conducted at more than 100 sites globally in 19 countries. The trial was designed to enroll 760 patients with advanced HCC who received prior sorafenib (Nexavar) and may have received up to two prior systemic cancer therapies for HCC and had adequate liver function. Enrollment of the trial was completed in September 2017. Patients were randomized 2:1 to receive 60 mg of cabozantinib once daily or placebo, and were stratified based on etiology of the disease (hepatitis C, hepatitis B, or other), geographic region (Asia vs other regions), and presence of extrahepatic spread and/or macrovascular invasion (yes or no). No crossover was allowed between the study arms.
The primary endpoint for the trial is overall survival, and secondary endpoints include objective response rate and progression-free survival. Exploratory endpoints include patient-reported outcomes, biomarkers, and safety.
Based on available clinical trial data from various published trials conducted in the second-line setting of advanced HCC, the CELESTIAL trial statistics for the primary endpoint of overall survival assumed a median overall survival of 8.2 months for the placebo arm. A total of 621 events provide the study with 90% power to detect a 32% increase in median overall survival (hazard ratio = 0.76) at the final analysis. Two interim analyses were planned and conducted at 50% and 75% of the planned 621 events.
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