Phase 3 Results of Cabozantinib in Hepatocellular Carcinoma Released

This morning, Ipsen and Exelixis, Inc. announced detailed results of the pivotal phase 3 CELESTIAL trial, evaluating cabozatinib in previously treated patients with advanced hepatocellular carcinoma (HCC).

The data will be presented in a late-breaking oral session at the 2018 American Society of Clinical Oncology (ASCO) GI Symposium being held in San Francisco this weekend.

HCC, the world’s third-leading cause of death due to cancer, affects less than 200,000 people in the United States, and is has a generally poor prognosis with 5-year survival rates ranging from 3% for advanced cancer to 31% for localized forms. It is often the result of a chronic hepatitis B infection, and is a primary malignancy of the liver that occurs mostly in patients with chronic liver disease and cirrhosis.

Presentation of it most frequently transpires in later stages with right-upper-quadrant pain, weight loss, and signs of decompensated liver disease.

Cabozantinib is a small molecule inhibitor of receptors, including VEGFR, MET and AXL, being developed to be administered orally. In preclinical models, it has been shown to inhibit the activity of these receptors, which are involved in normal cellular function and pathologic processes like tumor angiogenesis, invasiveness, metastasis and drug resistance.

By September 2017, the trial had enrolled 760 patients with advanced HCC who received prior sorafenib and may have received up to 2 prior systemic cancer therapies for HCC and had adequate liver function.

Results from the CELESTIAL study showed cabozantinib’s ability to provide a statistically significant and clinically meaningful improvement in overall survival (OS), the trial’s primary endpoint, when compared to placebo at the planned second interim analysis for the population of second- and third-line patients enrolled in this study. Median OS was 10.2 months in patients administered cabozantinib versus 8.0 months in those given placebo.

Additionally, median progression-free survival (PFS) was more than doubled, at 5.2 months with cabozantinib and 1.9 months with placebo. Disease control (partial response or stable disease) was achieved by 64% of the cabozantinib group compared with 33% of the placebo group.

Ghassan K. Abou-Alfa, M.D., Memorial Sloan Kettering Cancer Center, New York and lead investigator on CELESTIAL stresses the impact the drug could have if approved: “Patients with advanced hepatocellular carcinoma often have a poor prognosis and limited treatment options following prior systemic therapy,” he said. “The clinically significant benefits in both overall survival and progression-free survival shown in the CELESTIAL trial suggest that, if approved, cabozantinib could become an important addition to the treatment landscape for these patients.”

Dr Abou-Alfa will present the data during Oral Abstract B: Cancers of the Pancreas, Small Bowel, and Hepatobiliary Tract on Friday afternoon. Exelixis and Ipsen intend to submit a supplemental New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) in the first quarter of 2018.

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