Exelixis’ next-generation tyrosine kinase inhibitor zanzalintinib is being tested for colorectal cancer, renal cell carcinoma and head-and-neck cancer, with several readouts slated for the second half of 2025.
As cancer drug Cabometyx delivers another disappointing readout—this time in a Bristol Myers Squibb-partnered kidney cancer study—Exelixis is pinning its hopes on the next-generation tyrosine kinase inhibitor zanzalintinib.
Final results from the Phase III COSMIC-313 trial, presented over the weekend at the 2025 American Society of Clinical Oncology’s Genitourinary Cancers Symposium showed that tacking Cabometyx onto a doublet regimen with BMS’s Opdivo and Yervoy did not significantly improve overall survival (OS) in patients with intermediate- or poor-risk advanced renal cell carcinoma (RCC).
In fact, patients taking the Cabometyx combo saw a 2% increased risk of death. Median OS in this group was 41.9 months, as opposed to 42 months in patients who took the BMS doublet.
Exelixis Chief Medical Officer Amy Peterson first disclosed that COSMIC-313 missed its OS endpoint in August 2024, during the company’s second-quarter earnings report. At the time, she noted that while the Cabometyx triplet significantly improved progression-free survival in the trial, it “did not demonstrate an OS benefit over the control arm,” according to a transcript of the investor call.
Based on this result, Exelixis has “no plans to file this study for label extension,” Peterson said. Cabometyx is currently approved for the treatment of advanced RCC—including in combination with Opdivo in the first-line setting—and hepatocellular carcinoma.
COSMIC-313’s readout at ASCO GU comes after Cabometyx in September 2024 returned similarly underwhelming survival data in the Phase III CONTACT-02 study in metastatic castration-resistant prostate cancer. When combined with Roche’s Tecentriq, Cabometyx elicited a “numerical but not statistically significant improvement,” Exelixis said at the time.
Not all is bleak for Cabometyx, however. In August 2023, Exelixis was able to stop the pivotal Phase III CABINET trial of the drug in neuroendocrine tumors ahead of schedule after documenting “dramatic improvement in efficacy.” The FDA is currently reviewing Cabometyx in this indication, with a target action date of April 3.
Still, Exelixis appears to be planning to pivot to its next-generation cancer drug zanzalintinib, with CEO Michael Morissey saying in the company’s fourth-quarter business report last week that “we expect zanzalintinib to take center stage in 2025 as our next franchise opportunity.”
Analysts at William Blair, in a note to investors following Exelixis’ Q4 report, said that zanzalintinib could reach $5 billion in net U.S. sales in 2033. The drug is currently being developed for RCC, colorectal cancer, neuroendocrine tumors and head-and-neck cancer. Readouts are expected in the second half of this year, according to William Blair.
