Most patients with metastatic colorectal cancer (mCRC) have limited treatment options following standard-of-care therapy. VEGFR-tyrosine kinase inhibitors (TKIs) have demonstrated clinical activity in mCRC in combination with immune checkpoint inhibitors (ICIs), particularly in patients without liver metastases. The TKI zanzalintinib (XL092) targets VEGFR, MET and TAM kinases, proteins that are involved in tumor growth, angiogenesis, metastasis and immunosuppression. Zanzalintinib has immunomodulatory properties that may enhance response to ICIs. Presented is the design of STELLAR-303, a global, phase III, open-label, randomized study evaluating zanzalintinib plus atezolizumab versus regorafenib in patients with non-MSI-H mCRC who progressed during/after or are refractory/intolerant to standard-of-care therapy. The primary end point is overall survival in patients without liver metastases.Clinical Trial Registration: NCT05425940 (ClinicalTrials.gov).
Keywords: Phase III; XL092; atezolizumab; immune checkpoint inhibitor; liver metastases; metastatic colorectal cancer; microsatellite instability-high; regorafenib; tyrosine kinase inhibitor; zanzalintinib.
Metastatic colorectal cancer (mCRC) is cancer of the colon or rectum that has spread to other parts of the body, most often to the liver, lungs and abdomen. People with mCRC that has worsened after initial treatment have limited options. Zanzalintinib is a novel oral investigational drug that can slow or stop cancer growth. It works by blocking certain proteins that play important roles in the development, growth and spread of cancer. Zanzalintinib may also help improve the effectiveness of another class of cancer drugs called immune checkpoint inhibitors (ICIs), which work by activating the patient's immune system to fight cancer. Here, we describe the design of STELLAR-303, an ongoing study that is comparing the effects of combining zanzalintinib and an ICI drug called atezolizumab with an approved treatment for mCRC called regorafenib. About 900 participants with mCRC will be enrolled in the study worldwide. To be included in the study, participants must have mCRC that worsened after previous therapies and must not have a high level of microsatellite instability, which is a specific feature of some mCRCs. Participants will be randomly given one of the two treatments. The main goal of the study is to evaluate zanzalintinib plus atezolizumab compared with regorafenib by measuring the length of time participants are alive after starting treatment, specifically in patients with mCRC that has not spread to the liver. Additionally, the study will look at the side effects with each treatment. The study is currently seeking participants.