University of Pittsburgh Medical Center (UPMC) & UPMC Hillman Cancer Center, Pittsburgh, PA, USA.
Vall d'Hebron Hospital Campus & Institute of Oncology (VHIO), IOB-Quiron, UVic-UCC, Barcelona, Spain.
Future Oncol. 2024;20(24):1733-1743. doi: 10.1080/14796694.2024.2352276. Epub 2024 Jul 23.
Most patients with metastatic colorectal cancer (mCRC) have limited treatment options following standard-of-care therapy. VEGFR-tyrosine kinase inhibitors (TKIs) have demonstrated clinical activity in mCRC in combination with immune checkpoint inhibitors (ICIs), particularly in patients without liver metastases. The TKI zanzalintinib (XL092) targets VEGFR, MET and TAM kinases, proteins that are involved in tumor growth, angiogenesis, metastasis and immunosuppression. Zanzalintinib has immunomodulatory properties that may enhance response to ICIs. Presented is the design of STELLAR-303, a global, phase III, open-label, randomized study evaluating zanzalintinib plus atezolizumab versus regorafenib in patients with non-MSI-H mCRC who progressed during/after or are refractory/intolerant to standard-of-care therapy. The primary end point is overall survival in patients without liver metastases. NCT05425940 (ClinicalTrials.gov).
大多数转移性结直肠癌 (mCRC) 患者在接受标准治疗后，治疗选择有限。血管内皮生长因子受体-酪氨酸激酶抑制剂 (VEGFR-TKIs) 与免疫检查点抑制剂 (ICI) 联合应用在 mCRC 中显示出临床活性，特别是在无肝转移的患者中。TKI 赞纳替尼（XL092）靶向 VEGFR、MET 和 TAM 激酶，这些蛋白参与肿瘤生长、血管生成、转移和免疫抑制。赞纳替尼具有免疫调节特性，可能增强对 ICI 的反应。本文介绍了 STELLAR-303 的设计，这是一项全球性、三期、开放标签、随机研究，评估赞纳替尼联合阿替利珠单抗与regorafenib 在标准治疗后进展或不耐受/难治的非 MSI-H mCRC 患者中的疗效。主要终点是无肝转移患者的总生存期。NCT05425940（ClinicalTrials.gov）。
