News|Articles|May 28, 2026

FDA Grants Priority Review to Bezuclastinib Plus Sunitinib for Previously Treated GISTs

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Key Takeaways

Priority review follows prior breakthrough therapy designation and real-time oncology review, with FDA signaling no current plan for an advisory committee and no identified review issues to date.
PEAK randomized approximately 388 adults with unresectable/metastatic/locally advanced GISTs progressing on or intolerant to imatinib alone to sunitinib 37.5 mg daily plus/minus bezuclastinib after achieving bezuclastinib steady state.
Efficacy end points favored the combination: PFS HR, 0.50 (P < .0001); median PFS, 16.5 vs 9.2 months; and ORR, 46% vs 26% (P < .0001), with OS data not yet mature.
Safety showed higher grade 3 or greater ALT/AST elevations (10.8% vs 1.4%) and more discontinuations (7.4% vs 3.8%); transaminase increases were typically reversible, with no grade 4 events reported.

The FDA has accepted for review an NDA for bezuclastinib plus sunitinib in imatinib-pretreated GISTs, with a PDUFA date of November 30, 2026.

The FDA has accepted and granted a priority review to a new drug application (NDA) seeking the approval of bezuclastinib (CGT0486) in combination with sunitinib (Sutent) for the treatment of patients with gastrointestinal stromal tumors (GISTs) who have received prior treatment with imatinib (Gleevec).¹

A target action date of November 30, 2026, has been set by the FDA for the application under the Prescription Drug User Fee Act (PDUFA).

The application is supported by data from the phase 3 PEAK trial (NCT05208047).At the September 30, 2025, data cutoff, the bezuclastinib combination generated a 50% reduction in the risk of disease progression or death vs standard-of-care (SOC) sunitinib monotherapy (HR, 0.50; 95% CI, 0.39-0.65; P < .0001).² The median progression-free survival (PFS) was 16.5 months with the combination vs 9.2 months with sunitinib monotherapy. The objective response rate (ORR) was 46% vs 26% with these respective regimens (P < .0001). Overall survival (OS) data were immature at the time of this analysis.

Bezuclastinib previously received breakthrough therapy designation from the FDA for this indication and was also assigned real-time oncology review following the readout of initial data from PEAK in November 2025.¹

“We are excited to announce that our bezuclastinib NDA for patients with GIST has been accepted for review by the FDA,” Andrew Robbins, president and chief executive officer of Cogent Biosciences, stated in a news release. “We look forward to presenting the full, groundbreaking results from the PEAK trial at [the 2026 ASCO Annual Meeting] this weekend, and our preparations for expected bezuclastinib launches in both GIST and systemic mastocytosis later [in 2026] are well underway.”

Bezuclastinib Plus Sunitinib Is Under FDA Review in GIST

The FDA accepted a priority review to an NDA for bezuclastinib plus sunitinib in imatinib-pretreated GIST, assigning a PDUFA date of November 30, 2026, with no advisory committee planned.

In the phase 3 PEAK trial, the combination reduced the risk of disease progression or death by 50% vs sunitinib alone (HR, 0.50; 95% CI, 0.39-0.65; P < .0001), with a median PFS of 16.5 months vs 9.2 months.

Bezuclastinib also carries an FDA breakthrough therapy designation and Real-Time Oncology Review eligibility for this indication, and the NDA marks the first submission for a regimen to show a statistically significant advantage over an active comparator in GIST.

What was the design of the PEAK trial?

The global, randomized, multipart, phase 3 PEAK study evaluated the combination of bezuclastinib plus sunitinib against sunitinib monotherapy in adult patients with histologically confirmed locally advanced, metastatic, or unresectable GISTs who had progressed on or were intolerant to imatinib.³

The trial’s first part consisted of 2 arms: 1 to confirm the optimal dose of the updated bezuclastinib formulation in approximately 20 patients who had received at least 1 prior GIST therapy, and another to evaluate potential drug-drug interactions between bezuclastinib and sunitinib in approximately 18 patients who had received 2 or more prior tyrosine kinase inhibitors (TKIs).

Part 2 of the trial enrolled approximately 388 patients with disease progression on or intolerance to imatinib as their sole prior therapy. To qualify, patients needed a molecular pathology report, an ECOG performance status between 0 and 2, and at least 1 measurable lesion according to modified RECIST 1.1 criteria. These participants were randomly assigned 1:1 to receive a daily dose of sunitinib at 37.5 mg either as a monotherapy or in combination with bezuclastinib. Patients in the combination arm took bezuclastinib alone until steady state was achieved, after which both oral therapies were administered concurrently until protocol-specified discontinuation criteria were met.

Additionally, a separate substudy evaluated whether bezuclastinib acts as a CYP3A4 inducer in a distinct group of approximately 16 patients who had undergone at least 1 prior line of GIST therapy.

The primary end point for part 1 was pharmacokinetics, and the primary end point for part 2 was PFS. Secondary end points for the entire study included OS, ORR, time to response, duration of response, and safety.

What was the safety profile of bezuclastinib/sunitinib in PEAK?

Bezuclastinib plus sunitinib was generally well tolerated, with no unique risks identified beyond the known safety profile of sunitinib.^1,2 The most frequent grade 3 or higher treatment-emergent adverse effects (AEs) with the bezuclastinib combination vs sunitinib monotherapy included hypertension (29.4% vs 27.4%), neutropenia (15.2% vs 15.4%), elevated alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels (10.8% vs 1.4%), anemia (9.3% vs 4.8%), and diarrhea (7.8% vs 7.2%). Treatment-related AEs led to the discontinuation of study treatment in 7.4% of patients in the combination arm vs 3.8% in the monotherapy arm.

ALT/AST elevations were reported as predominantly transient, low-grade, non-serious, reversible, and asymptomatic. In the combination arm, these elevations led to bezuclastinib dose reductions in 12.7% of patients, and 1.5% of patients discontinued bezuclastinib due to ALT/AST elevations. All grade 3 ALT/AST elevations resolved, and no grade 4 elevations were reported.

What are the next steps for bezuclastinib plus sunitinib in GIST?

Regarding this priority review designation, the FDA has indicated that it does not currently plan to convene an advisory committee and has not identified any potential review issues at this time.¹

Full primary results from the PEAK trial are scheduled to be presented in an oral abstract session (Abstract 11500) at the 2026 American Society of Clinical Oncology Annual Meeting on May 30, 2026. If approved, bezuclastinib plus sunitinib would be the first treatment in GIST to demonstrate a statistically significant PFS benefit over an active comparator in a prospective phase 3 trial.

References

Cogent Biosciences announces FDA acceptance of new drug application (NDA) with priority review for bezuclastinib in combination with sunitinib for patients with GIST. News release. Cogent Biosciences. May 28, 2026. Accessed May 28, 2026. https://investors.cogentbio.com/news-releases/news-release-details/cogent-biosciences-announces-fda-acceptance-new-drug-0
Cogent Biosciences reports positive results from bezuclastinib PEAK phase 3 trial in gastrointestinal stromal tumors (GIST). News release. Cogent Biosciences. November 10, 2025. Accessed May 28, 2026. https://investors.cogentbio.com/news-releases/news-release-details/cogent-biosciences-reports-positive-results-bezuclastinib-peak
(Peak) a phase 3 randomized trial of CGT9486+sunitinib vs sunitinib in subjects with gastrointestinal stromal tumors. ClinicalTrials.gov. Updated May 22, 2026. Accessed May 28, 2026. https://classic.clinicaltrials.gov/ct2/show/NCT05208047