Exelixis Partners with Merck for Phase 3 Colorectal Cancer Trial Combining Zanzalintinib with Keytruda
核心洞察
Exelixis has entered a clinical development collaboration with Merck (搜索) to evaluate zanzalintinib combined with subcutaneous Keytruda Qlex (搜索) in the phase 3 STELLAR-316 study for resected stage II/III colorectal cancer (搜索) patients.
The trial will target high-risk patients who test positive for molecular residual disease following definitive therapy, representing a population with substantial unmet medical need.
STELLAR-316 is expected to initiate in mid-2026, with disease-free survival as the primary endpoint and circulating tumor DNA clearance as a key secondary endpoint.
Exelixis announced a clinical development collaboration with Merck (搜索) to supply Keytruda Qlex (搜索) (pembrolizumab and berahyaluronidase alfa-pmph) for combination with zanzalintinib in STELLAR-316, a planned phase 3 pivotal trial targeting patients with resected stage II/III colorectal cancer (搜索). Under the agreement, Exelixis will sponsor the trial while Merck provides the subcutaneous anti-PD-1 (搜索) therapy.
Targeting High-Risk Patient Population
STELLAR-316 will evaluate zanzalintinib with and without Keytruda Qlex (搜索) in patients with resected stage II/III colorectal cancer (搜索) who have tested positive for molecular residual disease (MRD+) following definitive therapy and show no radiographic evidence of disease. This represents a high-risk population with substantial unmet medical need, according to the companies.
The primary endpoint of the trial will be disease-free survival, with key secondary endpoints including circulating tumor DNA clearance. Exelixis expects to initiate STELLAR-316 in mid-2026.
"This collaboration with Merck (搜索) for the STELLAR-316 trial reflects the continued progress of the zanzalintinib clinical development program and is an important step forward in our efforts to advance a potentially new treatment option that may help prevent or delay metastatic progression for patients with resected colorectal cancer (搜索)," said Dana T. Aftab, Executive Vice President of Research and Development at Exelixis.
Precision Medicine Integration
In January 2026, Exelixis announced a collaboration with Natera, a global leader in cell-free DNA and precision medicine, for STELLAR-316. Natera will provide its Signatera assay to identify MRD-positive patients for trial enrollment, integrating precision medicine approaches into the program.
Zanzalintinib Development Program
Zanzalintinib is a novel oral kinase inhibitor that inhibits the activity of the TAM kinases (搜索) (TYRO3 (搜索), AXL (搜索), MER (搜索)), MET and VEGF receptors (搜索). These kinases play important roles in oncogenic processes, including tumor cell proliferation, metastasis, angiogenesis, drug resistance and evasion of antitumor immunity.
The FDA has already accepted Exelixis' New Drug Application for zanzalintinib in combination with atezolizumab (Tecentriq) for treating adult patients with metastatic colorectal cancer (搜索) who have been previously treated with fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy, and anti-EGFR (搜索) therapy for RAS wild-type disease. The FDA assigned a target action date of December 3, 2026.
Colorectal Cancer Burden
Colorectal cancer (搜索) is the third most common cancer and a leading cause of cancer-related deaths in the United States. Approximately 159,000 new cases will be diagnosed in the U.S. in 2026, with around 55,000 expected deaths from the disease. Nearly a quarter of colorectal cancer cases are diagnosed at the metastatic stage, at which point the five-year survival rate is around just 15%.
Expanding Partnership Portfolio
The collaboration with Merck (搜索) adds external validation to the zanzalintinib program and represents Exelixis' efforts to diversify its portfolio beyond its lead drug Cabometyx. In October 2024, Exelixis also collaborated with Merck to advance zanzalintinib, and in April 2026, Merck initiated LITESPARK-034, a phase 3 study evaluating zanzalintinib plus Welireg (belzutifan) versus Welireg and placebo in previously treated advanced renal cell carcinoma (搜索) patients.