The FDA has extended its review period for the new drug application (NDA) seeking the approval of zanzalintinib (XL092) in combination with atezolizumab (Tecentriq) for the treatment of adult patients with previously treated metastatic colorectal cancer (mCRC), according to a regulatory update from Exelixis.1
On September 10, 2026, the agency notified the company that it had extended the review after Exelixis submitted updated safety and efficacy data, which the FDA deemed a major amendment to the application. The submission moved the Prescription Drug User Fee Act (PDUFA) target action date to March 3, 2027; the initial date was December 3, 2026.
The NDA is supported by data from the phase 3 STELLAR-303 trial (NCT05425940), which met its dual primary end point of significantly improved overall survival (OS) with zanzalintinib plus atezolizumab vs regorafenib (Stivarga) in the intention-to-treat (ITT) population of patients with previously treated colorectal cancer.2 In the ITT population, the median OS was 10.9 months with the combination vs 9.4 months with regorafenib (HR, 0.80; 95% CI, 0.69-0.93; P = .0045).
The proposed indication covers adult patients with mCRC who have been previously treated with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, and, if RAS wild-type, anti-EGFR therapy.
Zanzalintinib is an investigational, next-generation oral TKI that targets vascular VEGF receptors, MET, and the TAM family of kinases, including AXL and MER.
How was the STELLAR-303 trial designed?
The global, randomized, open-label trial enrolled patients 18 years of age or older with confirmed metastatic adenocarcinoma of the colon or rectum who did not have documented microsatellite instability-high or mismatch repair–deficient disease.2 Patients were also required to have disease that had radiographically progressed on, or was refractory or intolerant to, prior standard-of-care treatment, including fluoropyrimidine plus irinotecan and oxaliplatin with or without an anti-VEGF antibody, an anti-EGFR antibody, and a BRAF inhibitor.
FDA Extends PDUFA Date for Zanzalintinib in mCRC
- The FDA extended the PDUFA target action data for new drug application seeking the approval of zanzalintinib plus atezolizumab for the treatment of adult patients with mCRC who have been previously treated with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, and, if RAS wild-type, anti-EGFR therapy.
- The target action date was extended to March 3, 2027, following the submission of additional data supprting the application.
- The initial PDUFA date was December 3, 2026.
A total of 901 patients were randomly assigned 1:1 to receive either oral zanzalintinib at 100 mg per day plus atezolizumab at 1200 mg intravenously every 3 weeks (n = 451) or oral regorafenib at 160 mg once per day on days 1 to 21 of each 28-day cycle (n = 450).
The trial’s dual primary end points were OS in the ITT population and OS among patients without liver metastases. Key secondary end points included progression-free survival (PFS), objective response rate, and safety.
What other data supported the NDA?
In a prespecified interim subgroup analysis of patients without liver metastases, the median OS was 15.9 months for the combination vs 12.8 months for regorafenib (stratified HR, 0.79; 95% CI, 0.61-1.03; P = .0875); these data remained immature. Consistent OS benefit was observed across most key subgroups.
The median PFS in the ITT population was 3.7 months with the combination vs 2.0 months with regorafenib (HR, 0.68; 95% CI, 0.59-0.79). Statistical significance for PFS could not be formally claimed under the prespecified hierarchical testing strategy, although the PFS improvement was generally consistent across subgroups.
Regarding safety, any-grade treatment-related adverse effects (TRAEs) occurred in 95% of patients treated with zanzalintinib plus atezolizumab vs 92% of those given regorafenib. Serious TRAEs occurred in 26% vs 10% of patients, respectively.
Treatment-related deaths included intestinal perforation (n = 2) with zanzalintinib, pneumonitis (n = 1) and renal failure (n = 1) with atezolizumab, altered consciousness (n = 1) with the combination, and jejunal perforation (n = 1) with regorafenib. The most common AEs observed with zanzalintinib plus atezolizumab vs regorafenib were diarrhea (50% vs 24%), hypertension (34% vs 26%), fatigue (33% vs 20%), nausea (31% vs 13%), and decreased appetite (30% vs 20%).
References
- Exelixis, Inc. Current report (Form 8-K). US Securities and Exchange Commission. September 11, 2026. Accessed September 11, 2026. https://ir.exelixis.com/static-files/0eed47bb-77b5-4c6e-ba9b-99a95320f1c0
- Hecht JR, Park YS, Tabernero J, et al; STELLAR-303 study investigators. Zanzalintinib plus atezolizumab versus regorafenib in refractory colorectal cancer (STELLAR-303): a randomised, open-label, phase 3 trial. Lancet. 2025;406(10517):2360-2370. doi:10.1016/S0140-6736(25)02025-2
