UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, CA 94143, USA.
Exelixis, Inc., Alameda, CA, USA.
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. ClinicalTrial.gov Registration: NCT03755791.
卡博替尼是一种口服酪氨酸激酶抑制剂，靶向 VEGFR、MET 和 TAM（TYRO3、AXL、MER）家族激酶受体。除了在肿瘤生长和血管生成中的作用外，卡博替尼的靶点还促进了免疫抑制的微环境。卡博替尼被批准用于接受过索拉非尼治疗的晚期肝细胞癌患者的单药治疗。由于其抗肿瘤和免疫调节特性，卡博替尼正在与免疫检查点抑制剂联合开发。这些联合治疗的早期研究显示出在实体瘤患者中具有有前途的抗肿瘤活性和耐受性。在这里，我们描述了 COSMIC-312 的原理和设计，这是一项 III 期研究，评估卡博替尼联合阿替利珠单抗（抗 PD-L1 单克隆抗体）与索拉非尼治疗初治晚期肝细胞癌患者的安全性和疗效。ClinicalTrials.gov 注册：NCT03755791。
