Zanzalintinib and Atezolizumab Combination Enhances Survival in Metastatic CRC

In a significant advancement for colorectal cancer treatment, the combination of zanzalintinib and atezolizumab has demonstrated a marked improvement in overall survival compared to regorafenib for patients with previously treated metastatic non-microsatellite instability-high (MSI-H) colorectal cancer. These findings arise from the ongoing phase 3 STELLAR-303 trial, with results pending detailed analysis for presentation at an upcoming medical conference.

The STELLAR-303 trial, which is registered under NCT05425940, involved 901 patients who were randomized to receive either zanzalintinib at 100 mg daily alongside atezolizumab at 1200 mg intravenously every three weeks, or regorafenib at 160 mg for the first 21 days of each 28-day cycle. The trial's dual primary endpoints were overall survival across the intent-to-treat (ITT) population and among patients without liver metastases.

Dr. Amy Peterson, Executive Vice President of Product Development & Medical Affairs at Exelixis and Chief Medical Officer, stated, "The STELLAR-303 results, which showed a survival benefit with the combination of zanzalintinib and atezolizumab vs regorafenib across all randomized patients with previously treated metastatic CRC, marks an important first milestone for our zanzalintinib pivotal development program." This exciting development is a critical step forward in the treatment landscape of advanced solid tumors, including colorectal cancer, kidney cancer, and neuroendocrine tumors.

The safety profile of the zanzalintinib and atezolizumab combination was consistent with earlier reports on each agent, and no new safety signals were observed during the trial. This aspect is crucial, as safety remains a cornerstone in the development of novel cancer therapies.

Key eligibility criteria for the trial included patients aged 18 years and older with histologically or cytologically confirmed adenocarcinoma of the colon or rectum and radiographical progression on prior standard-of-care therapies for metastatic colorectal cancer. Participants with prior exposure to regorafenib, trifluridine/tipiracil, or immune checkpoint inhibitors were excluded to ensure a clear assessment of the combination therapy's efficacy.

In addition to overall survival, secondary endpoints of the trial included progression-free survival, objective response rate, and duration of response, which will further elucidate the benefits of this treatment combination.

As the medical community awaits the full presentation of the STELLAR-303 trial results, the implications of these findings could reshape treatment protocols for metastatic colorectal cancer, offering hope to patients who have limited options. The potential for zanzalintinib to enhance the therapeutic landscape is substantial, especially given its design as a third-generation, orally available tyrosine kinase inhibitor targeting multiple receptor tyrosine kinases, including VEGF receptors, MET, AXL, and MER, thus expanding its utility across various malignancies.

In summary, the early data from the STELLAR-303 trial heralds a promising future for the treatment of metastatic colorectal cancer and highlights the need for continued research and exploration of combination therapies in oncology. With the upcoming presentation of detailed results, stakeholders in the medical field will be eager to evaluate the full impact of this innovative treatment strategy on patient outcomes.