Exelixis Announces Positive Phase 3 Trial Results for Zanzalintinib in Metastatic Colorectal Cancer

Exelixis announced positive topline results from the STELLAR-303 phase 3 trial, where zanzalintinib in combination with atezolizumab improved overall survival in patients with metastatic colorectal cancer compared to regorafenib. The safety profiles were consistent with previous observations, and no new safety signals were identified. The trial will proceed to the final analysis for the other dual primary endpoint of overall survival in patients without liver metastases.

June 19, 2025

Exelixis, Inc. (Nasdaq: EXEL) today announced positive topline results from the STELLAR-303 phase 3 pivotal trial. The study demonstrated a statistically significant improvement in overall survival (OS) for zanzalintinib in combination with atezolizumab (Tecentriq®) versus regorafenib in the intent-to-treat (ITT) population of patients with previously treated non-microsatellite instability (MSI)-high metastatic colorectal cancer (CRC).

The topline findings, as presented by the Independent Data Monitoring Committee, showed a survival benefit for the combination therapy compared to regorafenib. The trial will continue to the planned final analysis for the other dual primary endpoint of OS in patients without liver metastases (non-liver metastases, NLM).

The safety profiles of zanzalintinib in combination with atezolizumab and of regorafenib were generally consistent with previously observed data, and no new safety signals were identified. The ITT population included all randomized patients, regardless of the presence of liver metastases, while the NLM subgroup consisted of patients without active liver metastases at baseline.

Amy Peterson, M.D., Executive Vice President, Product Development & Medical Affairs, and Chief Medical Officer at Exelixis, commented, "The STELLAR-303 results, which showed a survival benefit with the combination of zanzalintinib and atezolizumab versus regorafenib across all randomized patients with previously treated metastatic colorectal cancer, marks an important first milestone for our zanzalintinib pivotal development program. We look forward to discussing the findings with regulatory authorities and presenting the detailed results at an upcoming medical conference."

Exelixis plans to submit detailed results of STELLAR-303 for presentation at an upcoming medical conference. Secondary endpoints of the trial include progression-free survival, objective response rate, and duration of response in both the ITT population and the NLM subgroup.

Zanzalintinib is a third-generation oral tyrosine kinase inhibitor that inhibits the activity of receptor tyrosine kinases involved in cancer growth and spread, including VEGF receptors, MET, AXL, and MER. The drug is currently being developed for the treatment of advanced solid tumors, including colorectal cancer, kidney cancer, head and neck cancer, and neuroendocrine tumors.

Colorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer-related deaths in the U.S. Approximately 154,000 new cases will be diagnosed in the U.S. in 2025, with around 53,000 expected deaths from the disease [1].

References:
[1] Exelixis, Inc. (2025). Exelixis Announces Zanzalintinib in Combination with an Immune Checkpoint Inhibitor Improved Overall Survival in STELLAR-303 Phase 3 Pivotal Trial in Patients with Metastatic Colorectal Cancer. Business Wire. Retrieved from https://www.businesswire.com/news/home/20250622399674/en/Exelixis-Announces-Zanzalintinib-in-Combination-with-an-Immune-Checkpoint-Inhibitor-Improved-Overall-Survival-in-STELLAR-303-Phase-3-Pivotal-Trial-in-Patients-with-Metastatic-Colorectal-Cancer