Sunitinib Malate

Cogent Biosciences is testing its star candidate in patients with advanced systemic mastocytosis, with a phase 3 trial set to read out in December.\n 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.

Cogent Biosciences’ share price more than doubled on Monday after its drug candidate halved the risk of death or disease progression in a late-stage trial of a type of rare tumor that grows in the connective tissue of the gastrointestinal tract. In the Phase 3 trial, Cogent’s drug bezuclastinib was added to Pfizer’s Sutent, a multi-kinase inhibitor used to treat second-line gastrointestinal stromal tumors (GISTs). Patients who got bezuclastinib had a median progression-free survival of 16.5 months, compared with 9.2 months on Sutent alone, the company said in a release . Cogent CEO Andrew Robbins described the data as “incredible” and said it should position the regimen as the standard of care for second-line GISTs. Investors appeared to agree: The company’s shares $COGT rose about 120% at market open on Monday. The 16.5-month PFS was well over a benchmark set by Stifel analysts, who wrote Sunday that a result of more than 13 months will be necessary “to maintain strong competitive footing.” Based on the results, the biotech said it plans to file an application with the FDA for bezuclastinib in the first half of next year. Cogent also expects to share detailed data from the trial, called the PEAK study, at a future scientific conference. The PEAK study enrolled hundreds of patients with GISTs who are either resistant or intolerant to Novartis’ Gleevec, a common treatment for the first-line or adjuvant setting. In another key secondary endpoint in the trial, 46% of patients treated with the bezuclastinib regimen in Cogent’s Phase 3 trial saw their tumors shrink, versus 26% of those given Sutent alone. Cogent isn’t the only company working on new options for GIST patients. GSK is developing IDRX-42, which it acquired from its original developer IDRx in February, in a deal worth $1 billion upfront. In a Phase 1b study, IDRX-42 produced a 15-month PFS in second-line GIST patients, according to a poster published on the Connective Tissue Oncology Society’s (CTOS) virtual platform over the weekend, which was cited by the Stifel analysts. Those data will be presented in detail at the CTOS annual congress later this week. GSK has posted a Phase 3 study on ClinicalTrials.gov that’s pitting single-agent IDRX-42 against Sutent in second-line GISTs, although it is not yet enrolling. If IDRX-42 ends up matching bezuclastinib’s efficacy in later studies, market dominance could come down to safety benefits, the analysts wrote. With bezuclastinib, the most common grade 3 or higher side effects in the PEAK trial included hypertension (29.4%), neutropenia (15.2%), elevated liver enzymes (10.8%), anemia (9.3%) and diarrhea (7.8%).