Regulatory Status of GIST Treatments and Practice Implications

Dr. Agulnik outlines bezuclastinib's regulatory trajectory, noting Breakthrough Therapy Designation granted in March 2026 based on PEAK topline results. This designation indicates the drug addresses unmet medical need with substantial improvement over available therapy. The New Drug Application was accepted under Real-Time Oncology Review with submission completed in April 2026.

If approved, bezuclastinib plus sunitinib would represent the first combination TKI regimen in GIST, fundamentally changing second-line practice patterns. Community oncologists would need to transition from sunitinib monotherapy to combination approaches, requiring updated toxicity management protocols and monitoring strategies.

Currently, expanded access programs provide treatment access for patients not enrolled in PEAK who are candidates for second-line therapy or beyond, including those who have failed multiple prior TKI treatments. This program allows community experience accumulation before potential approval.

The 4 existing FDA-approved agents retain their established roles in the treatment sequence, with ripretinib maintaining its position as standard of care in the post-third-TKI setting. The combination approach represents addition rather than replacement of current treatment options.

Approval timeline expectations suggest potential FDA action by fourth quarter 2026, with possible approval in early 2027 if regulatory review proceeds as anticipated. This timeline would provide community oncologists opportunity to prepare for practice integration through educational initiatives and protocol development.