At the 2026 Annual Meeting of the American Society of Clinical Oncology (ASCO) Andrew Wagner (Dana-Farber Cancer Institute), MD, PhD, presents findings from the phase 3 PEAK study for patients with advanced gastrointestinal stromal tumors (GIST) showing that combination therapy with bezuclastinib plus sunitinib – both KIT inhibitors that work against different KIT mutations – outperformed sunitinib alone.

GISTs are rare cancers that can arise anywhere in the gastrointestinal tract.

Most are driven by mutations that activate the KIT protein.

Evidence supporting the use of KIT inhibitors such as first-line imatinib and second-line sunitinib to treat advanced GIST emerged from Dana-Farber research.

While KIT inhibitors have improved outcomes, tumors still develop resistance, typically by developing additional KIT mutations.

Bezuclastinib inhibits common primary and secondary resistance mutations in advanced KIT-mutant GIST.

Previous Dana-Farber research showed it is safe to combine bezuclastinib with sunitinib.

In the study, 413 patients with advanced GIST who had received prior therapy with imatinib were randomized to either bezuclastinib plus sunitinib or sunitinib alone.

The combination reduced the risk of progression or death by 50 percent.

The overall response rate also improved from 26 percent with monotherapy to 46 percent with the combination.

The combination was also well tolerated by patients.

“These are dramatic results that support the biologic rationale that more complete inhibition of the spectra of KIT mutations in a given patient can provide better and more durable outcomes than using a single drug,” said Wagner, Deputy Chief Medical Officer and senior physician in sarcoma at Dana-Farber.

“If this combination is ultimately approved, it will become the new standard of care, replacing single-agent sunitinib, which has been the standard for about 20 years.”

Source: Dana-Farber Cancer Institute