Zanzalintinib

SEER reports that 23% of colorectal cancers are diagnosed at a distant stage, with five-year relative survival of 16.9%. The American Cancer Society estimates 158,850 new colorectal cancer cases in the United States in 2026 across all stages. In a metastatic colorectal cancer cohort, the 12-month cumulative incidence of major financial hardship was 71.3%, despite 98.0% of participants having insurance.

STELLAR-303 randomized 901 participants. Zanzalintinib plus atezolizumab produced median overall survival of 10.9 months versus 9.4 months with regorafenib in the intention-to-treat population, with a hazard ratio of 0.80 (95% confidence interval 0.69–0.93; P=0.0045). The final analysis in participants without active liver metastases did not establish statistical significance: hazard ratio 0.83 (95% confidence interval 0.66–1.05; P=0.1185). Grade 3 or higher treatment-related adverse events occurred in 268 of 446 participants (60%) receiving the combination and 161 of 434 (37%) receiving regorafenib. Treatment-related deaths were reported in five participants (1%) and one participant (<1%), respectively.

The pivotal trial supports an overall-survival benefit for zanzalintinib plus atezolizumab versus regorafenib in its intention-to-treat population, with a higher frequency of grade 3 or higher treatment-related adverse events. The later analysis without active liver metastases did not meet statistical significance. Zanzalintinib remains investigational in the cited regulatory evidence. The updated FDA target action date is March 3, 2027; that date is not an approval or a confirmed commercial launch date.