Exelixis' Zanzalintinib Shows Promise in Late-Stage Colorectal Cancer Trial

Exelixis, a prominent player in the pharmaceutical industry, has reported significant progress in its Phase III STELLAR-303 study, evaluating the efficacy of zanzalintinib in combination with Roche's Tecentriq for the treatment of metastatic colorectal cancer (mCRC). The results, presented at the 2025 European Society for Medical Oncology (ESMO) meeting and simultaneously published in The Lancet, demonstrate a notable improvement in overall survival rates, potentially setting a new standard for third-line treatment in mCRC.

Survival Benefit and Clinical Significance

The STELLAR-303 trial, involving over 900 patients with previously treated mCRC, showed that the combination of zanzalintinib and Tecentriq achieved a median overall survival (OS) of 10.9 months. This result surpassed the 9.4-month OS observed in the control group treated with Bayer's Stivarga. Furthermore, the 12- and 24-month OS estimates for the zanzalintinib group were 46% and 20%, respectively, compared to 38% and 10% in the Stivarga arm.

William Blair analysts have highlighted that these results "set a new survival bar in the third-line or later mCRC setting," potentially surpassing the current record held by Taiho Oncology's Lonsurf chemotherapy and Roche's Avastin combination, which yielded an OS of 10.8 months.

Safety Profile and Regulatory Outlook

While the efficacy data is promising, the safety profile of zanzalintinib warrants careful consideration. The study reported that 59% of patients in the zanzalintinib arm experienced grade 3/4 treatment-related toxicities, compared to 37% in the control group. Additionally, 18% of patients receiving zanzalintinib discontinued treatment due to side effects, and two deaths were attributed to the drug.

Despite these safety concerns, Exelixis is moving forward with its plans to submit a regulatory application for zanzalintinib by the end of 2025. This submission will mark a significant milestone for the company, as STELLAR-303 represents the first pivotal success from the zanzalintinib program.

Market Potential and Future Prospects

Analysts at William Blair have projected substantial market potential for zanzalintinib, estimating U.S. sales of $24 million in the first year following approval, with peak sales reaching $850 million in the mCRC indication alone. The firm has modeled a total of $4.5 billion in U.S. sales across all indications by 2033, underscoring the drug's importance to Exelixis' pipeline.

As the pharmaceutical industry continues to seek more effective treatments for advanced cancers, zanzalintinib's performance in the STELLAR-303 trial represents a significant step forward. However, the balance between efficacy and safety will likely be a key focus for regulators and clinicians as they evaluate the drug's potential role in the treatment landscape for metastatic colorectal cancer.