The US FDA has extended its review of the New Drug Application (NDA) for zanzalintinib, an oral kinase inhibitor, in combination with atezolizumab (Tecentriq) for previously treated metastatic colorectal cancer (mCRC) by three months, pushing the updated Prescription Drug User Fee Act (PDUFA) action date to March 3, 2027. The FDA classified updated safety and efficacy data submitted by Alameda, California-based Exelixis, Inc. (Nasdaq: EXEL) in response to an agency information request as a major amendment, triggering the extension.
The NDA is based on the Phase III STELLAR-303 trial, which randomized 901 patients 1:1 to zanzalintinib plus atezolizumab or regorafenib in previously treated non-microsatellite instability (non-MSI)-high mCRC. The combination demonstrated a statistically significant 20% reduction in the risk of death versus regorafenib in the intention-to-treat (ITT) population (stratified hazard ratio: 0.80; 95% confidence interval: 0.69–0.93; P=0.0045), with median overall survival (OS) of 10.9 months versus 9.4 months. These results were presented at the 2025 European Society for Medical Oncology Congress and published in The Lancet.
The trial carried dual primary OS endpoints — one in the full ITT population and one in patients without active liver metastases (non-liver metastases, NLM). The ITT endpoint was met, but the final NLM analysis reported in June 2026 produced a non-statistically significant trend favoring the combination (hazard ratio: 0.83; 95% CI: 0.66–1.05; P=0.1185), with median OS of 15.9 versus 12.7 months. The FDA accepted the NDA in February 2026 on the basis of the ITT result, covering the broader previously treated mCRC population.
Zanzalintinib inhibits the TAM kinases (TYRO3, AXL, MER), MET, and VEGF receptors. Exelixis designed the molecule as a successor to its approved cabozantinib (Cabometyx), with an improved pharmacokinetic half-life. The combination with atezolizumab, a PD-L1 checkpoint inhibitor, is intended to reduce immune evasion through TAM kinase blockade while suppressing angiogenesis.