ASCO CONFERENCE COVERAGE

Phase 3 PEAK Trial: Bezuclastinib Plus Sunitinib Improves PFS in Advanced GIST After Imatinib

Edited by:
Anthony Calabro, MA

Key Highlights

  • The randomized phase 3 portion of PEAK compared bezuclastinib plus sunitinib with sunitinib monotherapy in advanced GIST after prior imatinib.
  • Median progression-free survival was 16.5 months with bezuclastinib plus sunitinib vs 9.2 months with sunitinib alone.
  • Objective response rate was 46% with the combination vs 26% with monotherapy.
  • Overall survival data remained immature as of September 30, 2025.

Bezuclastinib plus sunitinib significantly improved median progression-free survival compared with sunitinib monotherapy in patients with advanced gastrointestinal stromal tumors (GIST) who had received prior imatinib, according to primary results from the phase 3 PEAK study that will be at the 2026 American Society of Clinical Oncology Annual Meeting in Chicago, IL.

PEAK was a multipart study that included dose confirmation, 2 drug-drug interaction assessments, and a randomized phase 3 portion, which was the focus of the abstract. Patients were randomized 1:1 to bezuclastinib 600 mg once daily plus sunitinib 37.5 mg once daily or sunitinib 37.5 mg once daily alone.

The primary endpoint was blinded independent central review–assessed median progression-free survival (mPFS). Key secondary end points were objective response rate (ORR) by blinded independent central review and overall survival. Crossover to combination therapy was permitted at blinded independent central review–confirmed progression.

Study Findings

A total of 413 patients were randomized, including 204 to bezuclastinib plus sunitinib and 209 to sunitinib monotherapy. Median age was 63 years, with a range of 30 to 88 years. Activating KIT mutations in exon 11 only were present in 59.6% of patients, and exon 9 only mutations were present in 14.0%.

The combination significantly improved mPFS compared with monotherapy, with a hazard ratio of 0.50 (95% CI, 0.39-0.65; P < .0001). Median PFS was 16.5 months with bezuclastinib plus sunitinib vs 9.2 months with sunitinib alone. ORR was also significantly improved with the combination, at 46% vs 26%, corresponding to a risk difference of 20% (95% CI, 10.6-28.6; P < .0001). As of September 30, 2025, overall survival data remained immature.

The incidence of adverse events was similar between arms. Grade 3 or higher adverse events were comparable, with no significant increase in common sunitinib-associated adverse events. Higher rates of grade 3 or higher ALT/AST elevations and anemia were observed with the combination and were manageable with dose modification. ALT/AST elevations led to bezuclastinib dose reductions in 13.2% and discontinuations in 1.5% of patients in the combination arm; all grade 3 hepatic adverse events resolved, and no grade 4 hepatic events occurred. No treatment-related adverse events led to death in the combination arm.

Clinical Implications

According to the study authors, combined KIT inhibition with bezuclastinib plus sunitinib significantly improved mPFS compared with sunitinib monotherapy, reducing the risk of progression or death by 50% and increasing ORR from 26% to 46%. The authors stated that the combination was well tolerated with no new safety findings.

Expert Commentary

“Combined KIT inhibition with bezuclastinib plus sunitinib significantly improved median progression-free survival vs sunitinib monotherapy, reducing the risk of progression or death by 50% and increasing objective response rate from 26% to 46%,” the researchers concluded.

Reference
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). Presented at: 2026 American Society of Clinical Oncology Annual Meeting; abstract 11500.