Exelixis Advances Cancer Treatment with FDA Acceptance of Zanzalintinib NDA

On February 2, 2026, Exelixis, Inc. (Nasdaq: EXEL) announced a major milestone as the U.S. Food and Drug Administration (FDA) accepted the New Drug Application (NDA) for zanzalintinib in combination with atezolizumab (Tecentriq®). This groundbreaking treatment is aimed at adult patients suffering from metastatic colorectal cancer (mCRC) who have previously undergone chemotherapy treatments involving fluoropyrimidine, oxaliplatin, and irinotecan, as well as anti-epidermal growth factor receptor (EGFR) therapy for RAS wild-type patients. The FDA has assigned a standard review timeline, with a Prescription Drug User Fee Act (PDUFA) target action date set for December 3, 2026.

Dr. Dana T. Aftab, Executive Vice President of Research and Development at Exelixis, expressed optimism regarding the NDA acceptance, stating, “We are encouraged by this meaningful progress toward addressing the needs of patients with previously treated metastatic colorectal cancer, for whom effective therapies have been limited and treatment outcomes remain poor.” Dr. Aftab emphasized that zanzalintinib could potentially offer a novel mechanism of action in a treatment landscape that has seen little advancement, providing hope to a patient population with dire outcomes.

The NDA is supported by data from the pivotal phase 3 STELLAR-303 trial, which demonstrated zanzalintinib in combination with atezolizumab significantly improved overall survival (OS) in patients with previously treated CRC compared to regorafenib. The trial, which included a total of 901 patients, evaluated the combination's efficacy in both the intention-to-treat (ITT) population and a subset of patients without liver metastases. Key results were presented at the 2025 European Society for Medical Oncology (ESMO) Congress and published in *The Lancet*. While the data on OS for patients without active liver metastases remains immature, the final analysis is expected in mid-2026.

STELLAR-303 is a global, multicenter, randomized, open-label study that enrolled 901 patients, dividing them into two groups: one receiving zanzalintinib with atezolizumab (451 patients) and the other receiving regorafenib (450 patients). The study's dual primary endpoints are OS in the ITT population and OS in the non-liver metastases subgroup. Secondary endpoints include progression-free survival (PFS) and objective response rates.

Zanzalintinib is an innovative oral kinase inhibitor targeting TAM kinases (TYRO3, AXL, MER), MET, and VEGF receptors, which are implicated in critical oncogenic processes such as tumor cell proliferation, metastasis, and drug resistance. By building on the success of Exelixis’ flagship product, cabozantinib, zanzalintinib aims to provide an improved pharmacokinetic profile while tackling advanced solid tumors, including colorectal cancer, kidney cancer, and neuroendocrine tumors.

Colorectal cancer remains a pressing health concern, ranking as the third most common cancer and a leading cause of cancer-related deaths in the United States. In 2026, approximately 159,000 new cases are expected, with around 55,000 fatalities attributed to the disease. The prognosis for patients diagnosed at the metastatic stage is particularly grim, with a five-year survival rate hovering around 15%. The liver is frequently the first site of metastasis, further complicating treatment outcomes.

Exelixis continues to showcase its commitment to advancing oncology through the development of next-generation therapies. With a robust pipeline focused on a diverse array of tumor types, the company aims to deliver transformative treatments that can significantly improve patient outcomes. As Exelixis prepares for the upcoming FDA review, the healthcare community eagerly awaits the potential approval of zanzalintinib, which could offer new hope to countless patients battling metastatic colorectal cancer.

In conclusion, the acceptance of the NDA for zanzalintinib in combination with atezolizumab marks a pivotal moment in the ongoing fight against colorectal cancer, underscoring Exelixis' dedication to innovation in cancer treatment.