Exelixis Zanzalintinib Combination Shows Modest Survival Benefit in Advanced Colorectal Cancer Trial
核心洞察
Exelixis' STELLAR-303 trial demonstrated a 1.5-month median overall survival improvement with zanzalintinib plus Tecentriq versus Stivarga in 901 patients with previously treated metastatic colorectal cancer (搜索).
The combination achieved 10.9 months median overall survival compared to 9.4 months with standard therapy, meeting the trial's primary endpoint after 18 months of follow-up.
Despite positive efficacy results, the combination showed higher toxicity with 59% of patients experiencing severe adverse events versus 37% in the control group.
Exelixis reported detailed results from its pivotal STELLAR-303 trial showing that the combination of zanzalintinib and Tecentriq extended overall survival in patients with previously treated metastatic colorectal cancer (搜索), though the modest benefit and increased toxicity led to a more than 10% drop in the company's share price Monday morning.
The Phase 3 trial enrolled 901 patients with metastatic colorectal cancer (搜索) whose disease had progressed after receiving other therapies. Participants were randomized to receive either Stivarga, a medicine commonly used for advanced colorectal cancer (搜索), or the combination of Tecentriq and zanzalintinib, Exelixis' experimental drug.
Primary Endpoint Results
After following patients for a median of 18 months, researchers reported a median overall survival of 10.9 months in the combination arm compared to 9.4 months in the Stivarga arm. The survival benefit was consistently observed across different patient subgroups, including those from different geographies, patients with or without RAS (搜索) genetic mutations, and those who had previously received anti-VEGF (搜索) therapies.
The results were published in The Lancet and presented at the European Society for Medical Oncology's annual meeting over the weekend. Notably, these survival figures come from an intent-to-treat population, which is often harder to demonstrate efficacy in.
Safety Profile Concerns
The combination therapy showed a concerning safety profile, with severe or life-threatening adverse events occurring in 59% of patients in the zanzalintinib arm compared to 37% in the Stivarga-treated group. The most common severe adverse events included hypertension, fatigue, diarrhea, and abnormal amounts of protein in patients' urine.
Investigators considered at least six deaths in the trial to be treatment-related: two attributed to zanzalintinib, two to Tecentriq, one to the combination, and one to Stivarga.
Regulatory and Market Outlook
Dana Aftab, head of Exelixis' research and development, stated that the results "provide further insight into the combination as a potential new option to extend survival in patients with previously treated metastatic colorectal cancer (搜索)." The company intends to file an approval application for zanzalintinib with the Food and Drug Administration before the end of the year.
However, market analysts expressed disappointment with the results. Yaron Werber, an analyst at TD Cowen, noted that key doctors in the colorectal cancer (搜索) field likely wanted to see a greater survival benefit and less toxicity. He observed that the pairing of zanzalintinib and Tecentriq was about as effective as the combination of Avastin and Lonsurf, which represents the current standard of care for third-line metastatic colorectal cancer (搜索).
Werber characterized the results as "underwhelming compared to investor expectations" and suggested that this combination is "likely going to be relegated to later lines" of colorectal cancer (搜索) therapy.