Author information

• ¹UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, CA 94143, USA.
• ²Exelixis, Inc., Alameda, CA, USA.
• ³Ipsen Bioscience, Inc., Cambridge, MA, USA.
• ⁴University of Hong Kong, Hong Kong, China.
• ⁵National Taiwan University College of Medicine, Taipei, Taiwan.
• ⁶Medical Oncology & Hematology Unit, Humanitas Cancer Center, Humanitas Clinical & Research Center, IRCCS, Rozzano, Milan, Italy.
• ⁷Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy.

Free article

Abstract

Cabozantinib is an oral tyrosine kinase inhibitor that targets VEGFR, MET and the TAM (TYRO3, AXL, MER) family of kinase receptors. In addition to their role in tumor growth and angiogenesis, cabozantinib targets promote an immune-suppressive microenvironment. Cabozantinib is approved as single-agent therapy for patients with advanced hepatocellular carcinoma who received prior sorafenib. Owing to its antitumor and immunomodulatory properties, cabozantinib is being developed in combination with immune checkpoint inhibitors. Early studies of these combinations have shown promising antitumor activity and tolerability in patients with solid tumors. Here, we describe the rationale and design of COSMIC-312, a Phase III study evaluating the safety and efficacy of cabozantinib in combination with atezolizumab (anti-PD-L1 monoclonal antibody) versussorafenib for treatment-naive patients with advanced hepatocellular carcinoma. Clinical Trial Registration: NCT03755791 (ClinicalTrials.gov).