Exelixis' TKI falls short in colorectal cancer subgroup as FDA reviews approval in all-comers

Exelixis' next-generation multikinase inhibitor zanzalintinib (the TKI) has failed to meet the dual primary endpoint in a subgroup of patients with previously treated metastatic colorectal cancer (mCRC) who did not have active liver metastases, despite numerical improvement in overall survival (OS). The FDA is still reviewing the drug in combination with atezolizumab for all-comers (intent-to-treat) mCRC patients, with a target decision date in December 2026.

In the phase 3 STELLAR-303 trial, the combination of zanzalintinib plus atezolizumab showed a statistically significant OS benefit vs regorafenib in the overall population, reducing the risk of death by about 20%. Median OS was 10.9 months versus 9.4 months in the control arm.

Within the non-liver metastases (NLM) subgroup, the final analysis showed only a 17% improvement in OS (median 15.9 vs 12.7 months), which did not reach statistical significance. Earlier, interim analyses had suggested a stronger benefit (around 23%), which has now eroded as data matured.

Analysts and company commentary suggest that the FDA may still approve the zanzalintinib–atezolizumab combination for third‑line or later mCRC because the trial met its primary endpoint in the all‑patients population, even though the subgroup without liver metastases did not meet its prespecified endpoint.

The FDA accepted Exelixis’ New Drug Application (zanzalintinib plus atezolizumab) for previously treated mCRC in early February 2026, assigning a Prescription Drug User Fee Act (PDUFA) target action date of December 3, 2026.