FDA Accepts NDA, Grants Priority Review to Bezuclastinib/Sunitinib in Pretreated GIST

The FDA has accepted and granted priority review to a new drug application (NDA) for bezuclastinib (CGT9486) in combination with sunitinib (Sutent) for the treatment of patients with gastrointestinal stromal tumors (GIST) who have received prior treatment with imatinib (Gleevec), according to a press release from the developer, Cogent Biosciences.¹

The federal agency has assigned a target action date of November 30, 2026, under the Prescription Drug User Fee Act (PDUFA). Based on the submission package, the FDA communicated that no advisory committee meeting is currently planned to review the application.

If approved, the combination regimen will help fill an unmet need in a patient population that has lacked new second-line treatment options for approximately 20 years. Bezuclastinib plus sunitinib is the first treatment ever to demonstrate a statistically significant advantage vs an active comparator in GIST.

Andrew Robbins, president and chief executive officer of Cogent Biosciences, stated: “We are excited to announce that our bezuclastinib NDA for patients with GIST has been accepted for review by the FDA. We look forward to presenting the full, groundbreaking results from the PEAK trial at [the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting] this weekend, and our preparations for expected bezuclastinib launches in both GIST and systemic mastocytosis later this year are well underway.”^1,2

What efficacy end points did bezuclastinib plus sunitinib meet in the PEAK trial?

The regulatory submission was supported by primary results from the pivotal phase 3 PEAK trial (NCT05208047), which evaluated the combination therapy against standard second-line monotherapy. At the September 30, 2025, data cutoff, the experimental combination met its primary end point, demonstrating a statistically significant improvement in progression-free survival (PFS) as assessed by blinded independent central review (BICR). The bezuclastinib combination produced a median PFS of 16.5 months compared with 9.2 months for patients treated with sunitinib monotherapy, representing a 50% reduction in the risk of disease progression or death (HR, 0.50; 95% CI, 0.39-0.65; P <.0001).

In addition to the primary survival advantage, key secondary end points favored the dual-blockade strategy over the active comparator. The objective response rate (ORR) per BICR reached 46% in the combination arm, nearly doubling the 26% observed in the sunitinib monotherapy arm. At the time of the primary analysis, overall survival data remained immature but continued to be monitored.

How was the phase 3 PEAK trial structured?

The PEAK study was a global, randomized, multi-part phase 3 clinical trial designed to optimize and evaluate the safety and efficacy of the combination regimen against standard single-agent therapy. The phase 3 randomized portion of the study (part 2) enrolled 413 patients with histologically confirmed locally advanced, unresectable, or metastatic GIST.²

Patients were assigned randomly assigned to the experimental combination cohort (n = 204) or to the monotherapy control arm (n = 209). The standardized dosing and treatment regimen required oral sunitinib at a fixed dose of 37.5 mg daily in both study arms. In the combination arm, patients also received bezuclastinib administered orally at a dose of 600 mg once daily. Crossover from the monotherapy arm to the bezuclastinib combination was permitted following BICR-confirmed disease progression.

To satisfy the patient eligibility criteria, those enrolled were adults who demonstrated disease progression on or intolerance to prior treatment with imatinib, possessed at least 1 measurable lesion per modified RECIST v1.1 criteria, and had an Eastern Cooperative Oncology Group performance status of 0 to 2.³

What safety and tolerability parameters were reported for the combination?

Safety outcomes from the PEAK trial indicated that the addition of bezuclastinib to standard sunitinib was generally well tolerated, presenting a profile consistent with the known safety benchmarks of the individual agents. The most frequent grade 3 or higher treatment-emergent adverse effects reported in the combination and monotherapy arms, respectively, 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%), and anemia (9.3% vs 4.8%).

The elevations in hepatic enzymes were characterized as transient, reversible, low grade, and largely asymptomatic. In the combination group, ALT or AST elevations led to bezuclastinib dose reductions in 12.7% of patients, while all grade 3 transaminase elevations were successfully resolved, and no grade 4 events occurred. Treatment was discontinued due to treatment-related adverse events by 7.4% of patients in the bezuclastinib plus sunitinib cohort compared with 3.8% of those in the sunitinib monotherapy group, with only 1.5% of combination-treated patients discontinuing due to liver enzyme abnormalities.

Prior to the NDA acceptance, the FDA granted breakthrough therapy designation to the bezuclastinib and sunitinib combination for this patient population in January 2026.⁴

References

1. 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 29, 2026. https://tinyurl.com/3krxakc9
2. Wagner AJ, Trent JC, Tap WD, et al. Primary results of the phase 3 peak study of bezuclastinib + sunitinib vs sunitinib monotherapy in advanced gastrointestinal stromal tumors (GIST). J Clin Oncol. 2026;44(suppl 16):11500. doi:10.1200/JCO.2026.44.16_suppl.11500
3. A phase 3 randomized trial of CGT9486+sunitinib vs. sunitinib in subjects with gastrointestinal stromal tumors (PEAK). ClinicalTrials.gov. Updated May 22, 2026. Accessed May 29, 2026. https://tinyurl.com/b3f93yj6
4. Cogent Biosciences announces breakthrough therapy designation for bezuclastinib in combination with sunitinib for patients with gastrointestinal stromal tumors (GIST). News release. Cogent Biosciences, Inc. January 26, 2026. Accessed May 29, 2026. https://tinyurl.com/mrxz9u36