New clinical data presented at the ESMO Congress 2025 highlight the potential of combining bezuclastinib (CGT9486) with sunitinib for patients with advanced gastrointestinal stromal tumors (GIST). The phase 1/2 study, sponsored by Cogent Biosciences, evaluated the safety and efficacy of this dual regimen in patients who had progressed on prior therapies, including imatinib.
According to the presented results, the combination demonstrated a manageable safety profile with no unexpected toxicities. Among evaluable patients, the overall response rate (ORR) was 20%, and the clinical benefit rate (CBR) reached 73% at 16 weeks. Notably, responses were observed in patients with KIT exon 9 mutations, a subgroup often associated with poorer outcomes on standard therapies.
Bezuclastinib is a selective KIT D816V and KIT exon 11/13/17 mutant inhibitor, while sunitinib is a multi-targeted tyrosine kinase inhibitor already approved for GIST after imatinib failure. The rationale for combining them is to overcome resistance mechanisms and broaden the coverage of KIT mutations.
These findings suggest that the combination could become a new treatment option in the advanced GIST paradigm, potentially moving into later-stage trials. However, larger randomized studies are needed to confirm the benefit and establish the optimal sequencing with existing therapies.
