FDA to Review New Drug Combo for Previously Treated Metastatic Colorectal Cancer

For patients living with metastatic colorectal cancer whose disease has progressed after standard chemotherapy, treatment options can be limited and outcomes remain challenging. A new regulatory step may bring a potential option closer to availability.

A news release from Exelixis, Inc. announced that the U.S. Food and Drug Administration (FDA) has accepted a new drug application for zanzalintinib (formerly known as XL092) in combination with the immunotherapy Tecentriq (atezolizumab) for adults with previously treated metastatic colorectal cancer.

The FDA assigned the application a standard review, with a target action date of Dec. 3, 2026. The submission is based on results from the phase 3 STELLAR-303 trial, which showed that the combination improved overall survival and significantly reduced the risk of death compared with Stivarga (regorafenib), a commonly used later-line therapy.

If approved, this combination would introduce a new treatment approach for patients whose cancer has continued to grow despite multiple prior lines of therapy.

Phase 3 trial shows survival benefit over standard therapy

The FDA submission is supported by findings from the global phase 3 STELLAR-303 study, which enrolled patients with metastatic colorectal cancer who had already received fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy. Patients with RAS wild-type disease had also previously received anti-epidermal growth factor receptor therapy.

In the trial, patients were randomly assigned to receive either zanzalintinib plus Tecentriq or Stivarga. Results showed a statistically significant improvement in overall survival for patients treated with the combination compared with Stivarga in the intention-to-treat population, which included all enrolled patients regardless of disease characteristics.

The study also demonstrated improvements in progression-free survival, meaning patients lived longer without their cancer worsening. These results were presented at the 2025 European Society for Medical Oncology Congress and later published in The Lancet, underscoring the strength of the data.

Although one of the dual primary endpoints, overall survival in patients without active liver metastases, has not yet reached maturity, the trial continues toward its planned final analysis, expected in mid-2026.

Why new treatments are needed in metastatic colorectal cancer

Colorectal cancer remains one of the most common and deadly cancers in the United States. In 2026, approximately 159,000 new cases are expected to be diagnosed, with an estimated 55,000 deaths attributed to the disease.

Nearly one in four patients is diagnosed after the cancer has already spread to distant organs. At this stage, the five-year survival rate is approximately 15%, highlighting the urgent need for more effective therapies. The liver is the most common site of spread, and liver metastases are associated with particularly poor outcomes.

Although advances in chemotherapy and targeted therapies have improved survival for some patients, treatment options become increasingly limited after multiple lines of therapy. For many patients, later-line treatments offer modest benefit, making new approaches especially important.

How the STELLAR-303 study was conducted

STELLAR-303 is a randomized, phase 3, open-label trial conducted at multiple centers around the world. A total of 901 patients with previously treated metastatic colorectal cancer were randomly assigned in to receive either the zanzalintinib and Tecentriq combination or Stivarga.

The study focused on patients with non-MSI-high disease, a group that generally does not respond well to immunotherapy alone. The dual primary endpoints were overall survival in the entire study population and overall survival in patients without active liver metastases at baseline. Secondary endpoints included progression-free survival, objective response rate and duration of response.

By comparing the combination against an established standard therapy, the study was designed to assess whether zanzalintinib plus Tecentriq could meaningfully improve outcomes in a difficult-to-treat population.

Patients enrolled in STELLAR-303 had metastatic colorectal cancer that had progressed despite multiple prior treatments. This reflects a real-world population with limited remaining options and significant unmet needs.

The trial included patients both with and without liver metastases, allowing researchers to explore how disease location may influence treatment benefit. Importantly, the overall survival benefit was observed across the intention-to-treat population, suggesting broad potential applicability if the therapy is approved.

Additional findings and what this means for patients

Zanzalintinib is an investigational oral drug that targets multiple kinases involved in cancer growth, spread and resistance to therapy. When combined with Tecentriq, an immune checkpoint inhibitor, the regimen aims to both slow tumor progression and enhance the immune system’s ability to recognize cancer cells.

“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,” said Dana T. Aftab, executive vice president of Research and Development at Exelixis, in the news release. “Zanzalintinib has the potential to become an important advancement in a challenging treatment landscape, and if approved, zanzalintinib in combination with atezolizumab would provide a novel mechanism of action for patients with previously treated metastatic colorectal cancer. We are deeply grateful to the patients, caregivers and investigators contributing to the clinical research in support of this application, and we look forward to collaborating with the FDA during the review process for our first new drug application for zanzalintinib.”

Patients are encouraged to discuss emerging treatment options and trial opportunities with their oncology team as part of shared decision-making.

References

1. “Exelixis Announces U.S. FDA Accepted the New Drug Application for Zanzalintinib in Combination with an Immune Checkpoint Inhibitor for Patients with Metastatic Colorectal Cancer,” by Exelixis, Inc. News release; Feb. 2, 2026.

Editor's note: This article is for informational purposes only and is not a substitute for professional medical advice, as your own experience will be unique. Use this article to guide discussions with your oncologist. Content was generated with AI and reviewed by a human editor.

For more news on cancer updates, research and education, don’t forget to subscribe to CURE®’s newsletters here.