Cogent’s PEAK Trial Shows Significant Survival Benefit in KIT-Driven GIST

Cogent Biosciences has reported detailed Phase 3 results from the pivotal PEAK trial (NCT05208047), showing that bezuclastinib combined with sunitinib significantly improved outcomes in patients with advanced KIT-driven gastrointestinal stromal tumors (GIST) previously treated with imatinib.

Presented at ASCO 2026, the regimen reduced the risk of disease progression or death by 50% compared with sunitinib alone (HR=0.50; 95% CI: 0.39–0.65; p<0.0001), extending median progression-free survival (PFS) from 9.2 months to 16.5 months and increasing objective response rates (ORR) from 26% to 46%.

The findings mark the first time a treatment has demonstrated a statistically significant advantage over an active comparator in a Phase 3 study of previously treated GIST, representing a major advance for patients whose disease has progressed following first-line imatinib therapy.

Broad Activity Across KIT Mutations

Bezuclastinib is a selective KIT inhibitor developed to minimize off-target activity while targeting key oncogenic KIT mutations that drive GIST growth. The combination demonstrated consistent benefit across all evaluated KIT mutation subgroups, including patients with primary and secondary mutations.

Durable long-term efficacy was also observed. Median PFS2, defined as the time from randomization to progression on subsequent therapy or death, was not reached in the combination arm compared with 21 months in the sunitinib arm (HR=0.57; 95% CI: 0.41–0.78). As of March 2026, the estimated mean treatment duration for patients receiving the combination had extended to 21.4 months, underscoring sustained clinical benefit.

Manageable Safety Profile

No new safety signals emerged, and the combination’s safety profile remained broadly consistent with the known profile of sunitinib. The most common Grade 3 or higher treatment-emergent adverse events included hypertension, neutropenia, elevated liver enzymes, anemia, and diarrhea.

Treatment discontinuation due to treatment-related adverse events occurred in 7.4% of patients receiving the combination compared with 3.8% of those receiving sunitinib alone. Investigators reported that hepatic adverse events were predominantly transient laboratory abnormalities that were reversible, largely asymptomatic, and not indicative of clinically significant liver injury.

Regulatory Outlook and Pipeline Expansion

The FDA has granted Priority Review to the New Drug Application for bezuclastinib plus sunitinib in patients with imatinib-resistant or imatinib-intolerant GIST. The application carries a Prescription Drug User Fee Act (PDUFA) target action date of November 30, 2026, and the agency has indicated that no advisory committee meeting is currently planned.

Beyond the regulatory submission, Cogent is expanding development into earlier treatment settings. The company recently initiated a new study evaluating the combination in first-line GIST patients with KIT exon 9 mutations, a subgroup that showed encouraging outcomes in the Phase 3 PEAK trial.

Expert and Clinical Outlook

Andrew Robbins, President and Chief Executive Officer of Cogent Biosciences, highlighted the combination’s clinically meaningful efficacy, consistent benefit across KIT mutation subgroups, and a safety profile broadly aligned with sunitinib. He noted that the Phase 3 results, together with the FDA’s Priority Review of the New Drug Application, position the regimen for a potential launch later this year if approved.

Andrew Wagner, M.D., Ph.D., Senior Physician at Dana-Farber Cancer Institute and Associate Professor of Medicine at Harvard Medical School, described the clinical activity observed with bezuclastinib plus sunitinib as particularly compelling for patients with KIT-driven GIST. He stated that the magnitude of benefit seen in PEAK supports the combination’s potential to become a new standard second-line treatment option for patients whose disease has progressed after imatinib.

Reference

Cogent Biosciences Announces Detailed Clinical Data from PEAK Phase 3 Trial with Bezuclastinib in Combination with Sunitinib in Gastrointestinal Stromal Tumors (GIST) at 2026 American Society of Clinical Oncology (ASCO) Annual Meeting – Cogent Biosciences, Inc.