Exelixis has secured supplies of subcutaneous Keytruda from Merck & Co. for a planned phase 3 study, completing the trio of contributors needed to run the colorectal cancer trial.
California-based Exelixis partnered with Natera on the trial in January. Natera is providing its molecular residual disease (MRD) test for use in the study, as it did for a Roche trial that supported a recent label expansion for Tecentriq. Echoing Roche’s strategy in a different indication, Exelixis will enroll patients with resected colorectal cancer who test positive for MRD but have no radiographic evidence of disease.
At the time of the Natera news, Exelixis said that patients who meet the enrollment criteria will receive zanzalintinib, its multitargeted tyrosine-kinase inhibitor, with or without an immune checkpoint inhibitor. Tuesday’s update revealed the identity of the immune checkpoint inhibitor.
Merck has agreed to supply Keytruda Qlex, the subcutaneous version of its blockbuster PD-1 inhibitor. The companies have a preexisting relationship, with Merck providing Keytruda for Exelixis’ phase 3 head and neck cancer trial under a 2024 agreement. But Exelixis’ previous work in colorectal cancer paired zanzalintinib with Roche’s Tecentriq.
Exelixis has filed for FDA approval of the zanzalintinib-Tecentriq combination in a pretreated, metastatic colorectal cancer patient population, with the agency set to reach a decision by Dec. 3. Clinical data on the combination in metastatic colorectal cancer informed the decision to start the MRD trial, Exelixis CEO Michael Morrissey, Ph.D., said at a Bank of America event last week.
“If zanza plus a checkpoint was effective at improving survival for patients with radiographic tumors, a large enough tumor mass where you could see it on an MRI or CT scan, then going after micrometastases with the same approach was a pretty good bet,” Morrissey said at the event.
Last year, researchers presented phase 3 data on Taiho Oncology’s Lonsurf in a similar patient population to that targeted in Exelixis’ planned study. Median disease-free survival was 9.3 months on the oral chemotherapy combination, compared with 5.5 months in the control cohort. Exelixis’ decision to target the patient population was informed more by its metastatic data than rivals’ results, Morrissey said.
Exelixis expects to start the study in mid-2026. Success could establish zanzalintinib, either with or without Keytruda, as a treatment for cancer patients who lack good options. The high-risk post-adjuvant population “is truly high risk,” Morrissey said, with some patients progressing within five months of their last round of adjuvant chemotherapy.