Exelixis’ oral tyrosine kinase inhibitor (TKI) was tied to a 20% reduced risk of death from colorectal cancer, appearing to validate the biopharma’s hopes of having another “franchise molecule” on its hands.
The phase 3 study saw 901 patients receive either Bayer’s Stivarga or Exelixis’ TKI zanzalintinib in combination with Roche’s checkpoint inhibitor Tecentriq. The biopharma announced back in June that overall survival (OS) in patients with previously treated non-microsatellite instability-high metastatic colorectal cancer was significantly longer on the combination than on Stivarga but held back the data.
Exelixis used a Monday presentation at the European Society for Medial Oncology (ESMO) Congress in Berlin to shed light on how zanzalintinib performed in the study. The readout showed median OS in the intent-to-treat population at a median 18-month follow-up was 10.9 months for the zanzalintinib-Tecentriq combination compared to 9.4 months for those on Stivarga and Tecentriq.
The result marks the first time a TKI has demonstrated improvement with an immune checkpoint inhibitor in this specific patient population, Dana Aftab, Ph.D., executive vice president of research and development at Exelixis, told Fierce.
“It was an absolute win [and] that’s what we were banking on,” Atfab said on the sidelines of the conference.
The study’s dual primary endpoint of OS in patients without liver metastases is expected to read out “sometime around the middle of next year,” Aftab said.
When it came to tolerability, 59% of patients receiving the zanzalintinib combo experienced a grade 3 or 4 treatment-related adverse event, compared to 37% of those on the Stivarga regimen. Aftab said this safety profile is “exactly in line with what’s seen with all” TKI-immune checkpoint inhibitor combo treatments.
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Exelixis has been developing zanzalintinib as the successor to its flagship oncology medicine Cabometyx, also known as cabozantinib. By improving attributes including pharmacokinetic half-life, the company has designed a molecule that it believes can win approval in a range of diseases and even exceed Cabometyx’s peak sales.
Like Cabometyx, the company sees zanzalintinib becoming a “franchise molecule” for gastrointestinal cancers, Aftab told Fierce.
“We already have the team in place to do that commercially and from the medical affairs side,” he added.
Exelixis has previously projected Cabometyx revenue will reach $3 billion in 2030 and that zanzalintinib could reach $5 billion in 2033 revenue. The company is gearing up to submit an approval application to the FDA in colorectal cancer this year, Aftab confirmed to Fierce, and is already evaluating the drug in a phase 3 study for non-clear cell renal cell carcinoma.
“Just like cabozantinib, which we built into a very large franchise, we have huge plans for zanza[lintinib],” he added. “This is just the start.”
