Cabozantinib in combination with atezolizumab versus sorafenib in treatment-naive advanced hepatocellular carcinoma: COSMIC-312 Phase III study design

Future Oncol. 2020 Jul;16(21):1525-1536. doi: 10.2217/fon-2020-0283. Epub 2020 Jun 3.


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) versus sorafenib for treatment-naive patients with advanced hepatocellular carcinoma. Registration: NCT03755791.

Keywords: atezolizumab; cabozantinib; hepatocellular carcinoma.

Publication types

  • Clinical Trial Protocol
  • Comparative Study

MeSH terms

  • Anilides / administration & dosage
  • Antibodies, Monoclonal, Humanized / administration & dosage
  • Antineoplastic Agents / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Carcinoma, Hepatocellular / drug therapy*
  • Clinical Trials, Phase III as Topic
  • Drug Interactions
  • Humans
  • Liver Neoplasms / drug therapy*
  • Pyridines / administration & dosage
  • Sorafenib / therapeutic use*


  • Anilides
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents
  • Pyridines
  • cabozantinib
  • atezolizumab
  • Sorafenib

Associated data