Shares of Exelixis were down more than 10% Monday morning as investors reacted to results from a large clinical trial that tested one of the biotechnology company’s experimental drugs in patients with hard-to-treat colorectal cancer.
The trial, titled STELLAR-303, enrolled 901 people with a certain kind of metastatic colorectal cancer, whose disease progressed after receiving other therapies. These participants were given either a medicine commonly used for advanced colorectal cancer, Stivarga, or a combination of Tecentriq and an Exelixis drug known as zanzalintinib.
In June, Exelixis disclosed that the trial had hit its central goal by showing the combination significantly improved “overall survival” — the gold standard in cancer drug research. More detailed data were published in The Lancet and presented over the weekend at the European Society for Medical Oncology’s annual meeting.
After following patients for a median of a year and a half, researchers reported a median overall survival of 10.9 months in the combination arm and 9.4 months in the Stivarga arm. Notably, these figures come from an “intent-to-treat population,” which is often harder to show efficacy in.
Exelixis said this survival benefit was consistently observed across different segments of patients who got the combination regimen. That includes patients from differing geographies, those with or without “RAS” genetic mutations, and those who had previously received another category of cancer drugs called anti-VEGF therapies.
The fresh results “provide further insight into the combination ... as a potential new option to extend survival in patients with previously treated metastatic colorectal cancer,” said Dana Aftab, head of Exelixis’ research and development, in a statement.
Aftab added that the company intends to file an approval application for zanzalintinib with the Food and Drug Administration before the end of the year.
Yaron Werber, an analyst at the investment bank TD Cowen, wrote in a note to clients that key doctors in the colorectal cancer field surely wanted to see a greater survival benefit and less toxicity in the study. For example, he noted how the pairing of Exelixis’ drug and Tecentriq was about as effective as a combination of Avastin and Lonsurf — the current standard of care for “third-line” metastatic colorectal cancer.
Researchers also reported severe or life-threatening adverse events in 59% of the study’s zanzalintinib arm, compared to 37% in the Stivarga-treated group. The most common of these events were 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 for zanzalintinib, two for Tecentriq, one for the combination and one for Stivarga.
Overall, the results are “underwhelming compared to investor expectations,” and this combination is “likely going to be relegated to later lines” of colorectal cancer therapy, Werber wrote.
