The Phase 3 STELLAR-303 trial tested zanzalintinib plus atezolizumab against regorafenib in patients with previously treated, non-MSI-high metastatic colorectal cancer. The study produced mixed results but achieved its main goal in the overall patient population.
The combination did not significantly improve overall survival in patients without active liver metastases, although survival was longer than with regorafenib alone (15.9 vs. 12.7 months). However, in the overall study population, the combination significantly reduced the risk of death, with median overall survival of 10.9 months compared with 9.4 months for regorafenib. Researchers noted that this is the first Phase 3 trial to demonstrate a significant overall survival benefit from an immunotherapy-based combination in this patient group.
The combination also improved progression-free survival (3.7 vs. 2.0 months) and disease control rates (54% vs. 41%).
Serious treatment-related side effects were more common with the combination, occurring in 60% of patients compared with 37% receiving regorafenib.