Cogent Biosciences has cleared another phase 3 hurdle for lead asset bezuclastinib, teeing up an approval submission for a form of gastrointestinal cancer in the first half of next year.
The tyrosine kinase inhibitor, in combination with approved cancer med sunitinib, was tied to an objective response rate (ORR) of 46% in patients with gastrointestinal stromal tumors who had not or could not benefit from Novartis' Gleevec. This ORR was significantly higher than the 26% rate for patients on sunitinib alone. Patients given the investigational combo also had a significantly higher median progression-free survival (mPFS) of 16.5 months compared to 9.2 months for the monotherapy, Cogent announced in a Nov. 10 release.
The phase 3 Peak trial enrolled around 442 patients, according to the federal trials database, and Cogent plans to present more data at a scientific conference in the first half of 2026.
The results “have far surpassed our expectations for the activity of this combination in patients with imatinib-resistant or intolerant GIST,” Cogent president and CEO Andrew Robbins said in the release. “With these incredible results, including a greater than seven-month improvement on mPFS—reducing the rate of progression or death by half—the bezuclastinib combination is poised to become the new standard of care for treatment of second-line GIST patients.”
The combination therapy produced no unique safety risks not already seen with sunitinib treatment alone, Cogent said in the release. In the combo arm, 7.4% of patients discontinued treatment due to treatment-related adverse events, compared to 3.8% in the monotherapy arm. The most severe side effects were grade 3 hypertension, neutropenia, increased liver enzymes, anemia and diarrhea.
Tyrosine kinase inhibitors are commonly used for GIST, with Gleevec—also known as imatinib—and sunitinib popular choices. By boosting sunitinib’s effectiveness with bezuclastinib, Cogent is hoping to compete with other later-line tyrosine kinase inhibitors like Bayer’s Stivarga, Deciphera’s Qinlock and Blueprint’s Ayvakit.
“Following regulatory approval, I expect the bezuclastinib combination to be rapidly adopted as the new standard of care treatment for the majority of patients in the second-line GIST setting,” Neeta Somaiah, M.D., an oncologist at the University of Texas MD Anderson Cancer Center, said in the release.
The GIST success follows an earlier phase 3 win in July, when bezuclastinib slashed symptom severity scores in patients with non-advanced systemic mastocytosis. The company has since aligned with the FDA on a new drug application submission for this indication, according to Cogent’s third-quarter earnings report, snagging a breakthrough therapy designation in October.
Cogent is also testing its star candidate in patients with advanced systemic mastocytosis, with a phase 3 trial set to read out in December, according to the Nov. 10 release.
Aside from bezuclastinib, the Massachusetts-based biotech is also pursuing an FGFR2/3 inhibitor called CGT4859 in a phase 1/2 trial for advanced solid tumors, with plans to launch an ErbB2 inhibitor called CGT4255 into a phase 1 dose-escalation study this month.