Exelixis has taken a major step forward in its colorectal cancer development pipeline by securing supplies of Merck’s Keytruda for an upcoming phase 3 clinical trial. As reported by Fierce Biotech, this partnership marks the completion of a powerful three-way collaboration designed to evaluate a promising new treatment approach for patients facing one of cancer care’s most challenging scenarios.
The Strategic Coalition
The trial represents a unified effort between three key players: Exelixis (developing the lead drug candidate), Natera (providing diagnostic technology), and Merck (supplying the immunotherapy). This coordinated approach reflects a growing trend in oncology where precision medicine, targeted drugs, and checkpoint inhibitors work together to maximize patient benefit.
Natera, which joined Exelixis in January, is contributing its molecular residual disease (MRD) test, the same diagnostic tool featured in a recent Roche trial that expanded the label for Tecentriq. This testing strategy represents a new frontier in cancer treatment: identifying and treating microscopic disease before it becomes visible on imaging scans.
Targeting a Critical Patient Population
The trial will focus on patients who have undergone surgery to remove colorectal cancer but face a high risk of recurrence. Specifically, researchers will enroll patients with resected colorectal cancer who test positive for MRD, meaning cancer cells are detectable at the molecular level, but show no radiographic evidence of disease on imaging.
This is a critically important population. As Exelixis CEO Michael Morrissey explained, these patients are “truly high risk,” with some progressing within just five months of completing standard chemotherapy. Traditional treatment options have limited these patients’ survival benefits, making new approaches essential.
The Treatment Approach
Study participants will receive zanzalintinib, Exelixis’ multitargeted tyrosine-kinase inhibitor, either alone or in combination with Merck’s Keytruda Qlex, the subcutaneous formulation of its blockbuster PD-1 checkpoint inhibitor. The combination strategy mirrors Roche’s successful approach, applying lessons learned from metastatic disease to the challenging MRD setting.
Building on Strong Data
Exelixis’ confidence in this approach stems from clinical evidence already in hand. The company has submitted zanzalintinib combined with Tecentriq for FDA approval in pretreated, metastatic colorectal cancer, with an agency decision expected by December 3.
“If zanza plus a checkpoint was effective at improving survival for patients with radiographic tumors, then going after micrometastases with the same approach was a pretty good bet,” Morrissey noted at a recent financial conference.
The Competitive Landscape
While rivals have explored similar territory, Taiho Oncology recently reported phase 3 data on Lonsurf in an analogous patient population, Exelixis’ decision-making was primarily informed by its own metastatic colorectal cancer data rather than competitors’ results.
What’s Next
Exelixis expects to launch the trial in mid-2026. Success could establish zanzalintinib, potentially with Keytruda, as a transformative option for patients lacking effective treatments. For a population currently facing poor prognosis and limited options, this partnership offers renewed hope for meaningful survival improvements.
The collaboration between Exelixis, Natera, and Merck exemplifies modern oncology development, combining precision diagnostics, targeted therapy, and immunotherapy to address an unmet medical need.
