New positive data for zanzalintinib plus Tecentriq (atezolizumab) shows statistically significant improvements in overall survival versus Stivarga (regorafenib) in patients with previously treated non-microsatellite instability (MSI)-high metastatic colorectal cancer who were enrolled on a clinical trial, according to a news release.
Results come from the STELLAR-303 phase 3 pivotal trial’s intent-to-treat population.
“The STELLAR-303 results, which showed a survival benefit with the combination of zanzalintinib and atezolizumab versus regorafenib across all randomized patients with previously treated metastatic colorectal cancer, marks an important first milestone for our zanzalintinib pivotal development program,” Dr. Amy Peterson said in the news release. “We look forward to discussing the findings with regulatory authorities and presenting the detailed results at an upcoming medical conference.”
Peterson is the executive vice president of Product Development & Medical Affairs, and chief medical officer at Exelixis, the company that produces zanzalintinib.
The safety of zanzalintinib in combination with Tecentriq and of Stivarga were generally consistent with what has been seen in previous studies, and no new safety signals were identified.
The trial will continue to the planned final analysis for the other dual primary endpoint of overall survival in patients without liver metastases (also referred to as the non-liver metastases subgroup), as per the release.
The intent-to-treat population included all randomized patients, regardless of whether they had liver metastases. The non-liver metastases subgroup included patients who did not have active liver metastases at the start of the study, as determined by the investigator.
Glossary
Microsatellite instability (MSI)-high: genetic feature of some cancers linked to better response to immunotherapy; non-MSI-high cancers often respond differently.
Overall survival: time from treatment start or diagnosis until death from any cause.
Progression-free survival: time during and after treatment that a patient lives without cancer growing or spreading.
Overall response rate: percentage of patients whose cancer shrinks or disappears after treatment.
Duration of response: length of time a treatment keeps cancer under control after it first responds.
Secondary endpoints of the STELLAR-303 study include progression-free survival, objective response rate, and duration of response in both the intent-to-treat population and the non-liver metastases subgroup. Exelixis plans to present full results from STELLAR-303 at an upcoming medical conference.
Colorectal cancer is the third most common cancer in the U.S. and often spreads to the liver, where survival drops significantly, especially when diagnosed at a metastatic stage, as per the release. The 16.2% 5-year survival rate of metastatic colorectal cancer drops under 14% with the presence of liver metastases when treated with palliative chemotherapy.
More Information on the STELLAR-303 Trial
STELLAR-303 is a global, multicenter phase 3 study evaluating treatment options for people with previously treated metastatic colorectal cancer that is not MSI-high. In this open-label trial, 901 patients were randomly assigned to receive either the investigational drug zanzalintinib (100 milligrams) plus Tecentriq or Stivarga, according to the release.
The study had two primary endpoints which are overall survival in both the full study population and in the subgroup of patients without liver metastases, as assessed by investigators at the start of the trial.
What is Zanzalintinib?
Zanzalintinib is an investigational third-generation oral tyrosine kinase inhibitor designed to block several key receptor tyrosine kinases involved in cancer development and progression, including VEGF receptors, MET, AXL and MER, as per the release. These targets play roles in both normal cellular activity and cancer-related processes such as tumor growth, metastasis, new blood vessel formation (angiogenesis), and resistance to treatments like immune checkpoint inhibitors.
This experimental therapy builds on the established target profile of Cabometyx and Cometriq (cabozantinib), aiming to improve certain characteristics — such as pharmacokinetic half-life — while potentially offering broader anti-tumor activity. Zanzalintinib is being evaluated in clinical trials for a range of advanced solid tumors, including colorectal, kidney, head and neck and neuroendocrine cancers.
As of now, zanzalintinib has not been approved for any indication and remains under investigation in ongoing studies.
Reference:
“Zanzalintinib in Combination with an Immune Checkpoint Inhibitor Improved Overall Survival in STELLAR-303 Phase 3 Pivotal Trial in Patients with Metastatic Colorectal Cancer” Exelixis press release via Business Wire. https://ir.exelixis.com/news-releases/news-release-details/exelixis-announces-zanzalintinib-combination-immune-checkpoint
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