A Phase 3 trial, STELLAR-303, shows that combining zanzalintinib (XL092) with atezolizumab (Tecentriq) extends survival in patients with metastatic colorectal cancer compared with standard treatment regorafenib (Stivarga). Patients previously treated with chemotherapy and who were not MSI-high lived 10.9 months on the combination versus 9.4 months on regorafenib, with slower disease progression (3.7 vs. 2.0 months) and higher disease control (54% vs. 41%).
The benefit was most pronounced in patients without liver metastases, who reached 15.9 months versus 12.7 months. Zanzalintinib blocks multiple cancer-growth pathways, while atezolizumab boosts the immune response. The survival advantage was consistent across patient subgroups, including those with various mutations or prior anti-VEGF therapy.
Side effects were manageable and similar to other tyrosine kinase inhibitor plus immunotherapy combinations, including high blood pressure, diarrhea, nausea, and low appetite, with less hand–foot syndrome than regorafenib. This combination offers a promising new option for advanced colorectal cancer with limited treatments.