FDA Accepts Supplemental New Drug Application for Cabozantinib in Previously Treated Advanced Hepatocellular Carcinoma
On May 29, the U.S. Food and Drug Administration (FDA) accepted for filing the supplemental new drug application (sNDA) for cabozantinib (Cabometyx) tablets as a treatment for patients with previously treated advanced hepatocellular carcinoma (HCC). The filing has been assigned a Prescription Drug User Fee Act (PDUFA) action date of January 14, 2019.
“Patients with this aggressive form of advanced liver cancer urgently need new treatment options after they progress on first-line therapy,” said Gisela Schwab, MD, President, Product Development and Medical Affairs and Chief Medical Officer, Exelixis. “The acceptance of our sNDA filing for cabozantinib is a critical step forward as we work to help address this unmet need, and we intend to work closely with the FDA as they review the application.”
An sNDA is an application to the FDA that, if approved, will allow a drug sponsor to make changes to a previously approved product label, including modifications to the indication. Exelixis announced they submitted the sNDA for the treatment of previously treated advanced HCC to the FDA in March 2018 based on results from the phase III CELESTIAL trial of cabozantinib in patients with advanced HCC who received prior sorafenib (Nexavar).
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 (and may have received up to two prior systemic cancer therapies for HCC) and had adequate liver function. Enrollment 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 disease etiology (hepatitis C, hepatitis B, or other), geographic region (Asia vs other regions), and the presence of extrahepatic spread and/or macrovascular invasion (yes or no). No crossover was allowed between the study arms during the blinded treatment phase of the trial.
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.
In October 2017, Exelixis announced that the independent data monitoring committee for the CELESTIAL study recommended the trial be stopped for efficacy following review at the second planned interim analysis, with cabozantinib providing a statistically significant and clinically meaningful improvement in overall survival compared with placebo in patients with previously treated advanced HCC. In March 2017, the FDA granted Orphan Drug designation to cabozantinib for the treatment of advanced HCC.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
