Exelixis has announced that the phase 3 CELESTIAL trial results have been accepted as a late-breaking presentation at the 2018 ASCO-GI Symposium, which is being held January 18–20, 2018 in San Francisco. Detailed results from CELESTIAL, the randomized, double-blind, placebo-controlled study of cabozantinib versus placebo in patients with advanced HCC who have received prior treatment with sorafenib, will be presented during Oral Abstract Session B: Cancers of the Pancreas, Small Bowel, and Hepatobiliary Tract on Friday, January 19, 2018.

Oral Presentation on Cabozantinib (C) versus placebo (P) in patients (pts) with advanced hepatocellular carcinoma (HCC) who have received prior sorafenib: results from the randomized phase 3 CELESTIAL trial. Ghassan K. Abou-Alfa, MD, Memorial Sloan-Kettering Cancer Center, New York

On October 16, 2017, Exelixis announced that the CELESTIAL trial met its primary endpoint of overall survival (OS), with cabozantinib providing a statistically significant and clinically meaningful improvement in OS compared with placebo in patients with advanced HCC. The independent data monitoring committee for the study recommended that the trial be stopped for efficacy following review of the second planned interim analysis.

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 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 versus other regions) and presence of extrahepatic spread and/or macrovascular invasion (yes or no). No cross-over was allowed between the study arms.

The primary endpoint for the trial is OS, 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 OS assumed a median OS of 8.2 months for the placebo arm. A total of 621 events provide the study with 90 percent power to detect a 32 percent increase in median OS (HR = 0.76) at the final analysis. Two interim analyses were planned and conducted at 50 percent and 75 percent of the planned 621 events.