On January 7, 2026 Exelixis, Inc. (Nasdaq: EXEL) and Natera (Nasdaq: NTRA), a global leader in cell-free DNA and precision medicine, reported their collaboration on the planned Exelixis-sponsored STELLAR-316 trial. This randomized phase 3 pivotal trial will evaluate zanzalintinib, Exelixis’ novel oral kinase inhibitor, with and without an immune checkpoint inhibitor, in patients with resected stage II/III colorectal cancer (CRC).
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Using Natera’s Signatera test following completion of definitive therapy*, patients with CRC who test positive for molecular residual disease (MRD) and have no radiographic evidence of disease will be eligible for enrollment in the STELLAR-316 trial. Working with patients and their providers, this trial will be fully enrolled with patients who are receiving commercial Signatera testing as part of their routine standard of care.
The primary endpoint of STELLAR-316 is disease-free survival. Signatera will also be used for longitudinal monitoring of circulating tumor DNA clearance, one of the secondary endpoints of the trial. Exelixis expects to initiate STELLAR-316 in mid-2026.
CRC is the third most common cancer and the second leading cause of cancer-related deaths in the U.S.1 Of the approximately 89,000 stage II/III colorectal cancer cases projected for 2035,2 about 20% of these patients are expected to remain MRD-positive following definitive therapy.3 Patients with stage II/III CRC who are MRD-positive have been shown to experience worse outcomes in multiple clinical studies3,4,5 and there are no established or approved therapies for this specific patient population in the U.S.
"Patients with colorectal cancer who are MRD-positive following definitive therapy face a high risk of recurrence, underscoring the urgent need for new treatment options that can help prevent clinical metastatic progression," said Dana T. Aftab, Ph.D., Executive Vice President, Research and Development, Exelixis. "STELLAR-316 is our second pivotal trial of zanzalintinib in patients with CRC and represents our continued commitment to addressing unmet needs in this patient population by conducting rigorous trials with the potential to improve standards of care. We are excited to collaborate with Natera on STELLAR-316, which, if successful, could make zanzalintinib the first MRD-guided treatment for these patients."
"Exelixis and Natera’s collaboration on STELLAR-316 underscores both companies’ commitment to advancing new approaches to treat CRC," said John Simmons, Ph.D., Global Vice President, Biopharma, Natera. "Leveraging Signatera to inform trial enrollment will help to identify high-risk patients earlier, enabling intervention when disease burden is lower – and importantly, with the potential to improve clinical outcomes."
About Zanzalintinib
Zanzalintinib is a novel oral kinase inhibitor that inhibits the activity of the TAM kinases (TYRO3, AXL, MER), MET and VEGF receptors. These kinases play important roles in oncogenic processes including tumor cell proliferation, metastasis, angiogenesis, drug resistance and evasion of antitumor immunity. With zanzalintinib, Exelixis sought to build upon its extensive experience with the target profile of cabozantinib, the company’s flagship medicine, while improving key characteristics, including pharmacokinetic half-life. Zanzalintinib is currently being developed for the treatment of advanced solid tumors, including colorectal cancer, kidney cancer and neuroendocrine tumors.
Exelixis recently confirmed it has submitted a New Drug Application to the U.S. Food & Drug Administration for zanzalintinib for the treatment of patients with previously treated metastatic colorectal cancer, when used in combination with atezolizumab (Tecentriq). The regulatory filing was based on positive results from the phase 3 STELLAR-303 pivotal trial, which met one of its dual primary endpoints, with the combination of zanzalintinib and atezolizumab demonstrating a statistically significant reduction in the risk of death versus regorafenib in the intention-to-treat population at the final analysis. An overall survival (OS) benefit with the combination was consistently observed across pre-specified subgroups, including geographic region, RAS status, liver involvement and prior anti-VEGF therapy. Data pertaining to the other dual primary endpoint, OS in patients without liver metastases (non-liver metastases or NLM), were immature at the data cutoff. A prespecified interim analysis showed a trend in OS favoring the combination. The trial will proceed to the planned final analysis for this endpoint, which is expected in mid-2026, based on current event rates.
Zanzalintinib is an investigational agent that is not approved for any use and is the subject of ongoing clinical trials.
About CRC
CRC is the third most common cancer and the second leading cause of cancer-related deaths in the U.S.1 Approximately 154,000 new cases will be diagnosed in the U.S. with around 53,000 expected deaths from the disease in 2025.1 CRC is most frequently diagnosed among people aged 65-74 and is more common in men and in people of non-Hispanic American Indian/Alaska Native descent.6 Nearly a quarter of CRC cases are diagnosed at the metastatic stage, at which point the five-year survival rate is just 16.2%.6 The liver is the most common site for CRC metastasis. Liver metastases significantly impact survival, with a median five-year survival rate of less than 14% when treated with palliative chemotherapy.
(Press release, Exelixis, JAN 7, 2026, View Source [SID1234661800])