Dr Trent on the Efficacy of Bezuclastinib Plus Sunitinib in Pretreated GIST

Jonathan C. Trent, MD, PhD, professor of medicine, associate director, Clinical Research, director, Bone and Soft-Tissue Sarcoma Group, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, discusses the findings from part 1 of the phase 3 PEAK trial (NCT05208047), which evaluated the combination of bezuclastinib (CGT9486) and sunitinib (Sutent) in patients with pretreated gastrointestinal stromal tumors (GIST).

PEAK is an open-label, randomized, multicenter trial. In part 1a, all patients (n = 19) received bezuclastinib at 300 mg or 600 mg once per day plus sunitinib at 37.5 mg per day, and a selected dose was then evaluated in patients enrolled in part 1b (n = 23) to examine the drug-to-drug interaction between the 2 agents. In part 2, which is ongoing, patients are being randomly assigned to bezuclastinib at 600 mg once per day plus sunitinib at 37.5 mg once per day or sunitinib alone.

Findings presented at the 2024 ASCO Annual Meeting showed that among all evaluable patients treated between part 1a and part 1b of the study experienced a median progression-free survival (PFS) of 10.2 months. Notably, those receiving the combination therapy in the second line (n = 7) achieved a median PFS of 19.4 months. Patients in the overall population received a median of 2.5 prior lines of therapy (range, 1-6). All patients received prior treatment with imatinib (Gleevec).

Additional data showed that patients evaluable for response (n = 40) experienced an overall response rate (ORR) of 27.5%, which was comprised exclusively of partial responses. Stable disease was observed in 57.5% of patients, and the disease control rate was 80.0%. In evaluable patients who received only 1 prior line of therapy (n = 6), the ORR was 33.3%, and the DCR was 100%. Those respective rates were 26.5% and 76.5% for evaluable patients who received 2 or more prior TKIs (n = 34).