Patients with previously treated metastatic colorectal cancer may benefit from a new combination therapy of zanzalintinib and the immunotherapy drug Tecentriq, according to results from the Phase 3 STELLAR-303 trial.
The study enrolled 901 patients whose cancer had progressed after standard treatments. Among all patients in the trial, the combination reduced the risk of death by 20% compared with regorafenib and improved median overall survival from 9.4 months to 10.9 months.
In patients without active liver metastases, the combination showed a longer median overall survival of 15.9 months versus 12.7 months with regorafenib. However, this difference did not reach statistical significance.
The treatment was associated with more side effects than regorafenib. Severe treatment-related adverse events occurred in 60% of patients receiving the combination, compared with 37% of those receiving regorafenib. The most common serious side effects included high blood pressure, fatigue, and diarrhea.
Zanzalintinib is an oral targeted therapy designed to block several cancer-related pathways, including TAM kinases, MET, and VEGF receptors. The FDA is currently reviewing the combination therapy, with a decision expected by December 2026.