Phase 3 Clinical Trial of 300 mg Vamotinib Directly Compared with High-Dose Imatinib in Chronic Myeloid Leukemia Patients in Chronic Phase with Failure of Standard-Dose Imatinib: Interim Analysis

BACKGROUND. Resistance and intolerance to treatment for Ph+ chronic myeloid leukemia (CML) after failure of imatinib therapy remain an issue in clinical oncohematology. Vamotinib (former name PF-114) is a domestic innovative third-generation BCR::ABL1-tyrosine kinase inhibitor (TKI). Previous pre-clinical studies and a phase 1 clinical trial demonstrated the efficacy and safety of this drug in Ph+ CML therapy, also in patients with resistance and/or intolerance to second-generation TKIs as well as with T315I mutation. AIM. To study vamotinib efficacy and safety profile compared with high-dose imatinib in terms of the major molecular response (MMR) rate after 12-month treatment in CML patients in chronic phase (CP). MATERIALS & METHODS. The present phase 3 trial is prospective, randomized, open-label, multi-center, and international (Russia and India). CML patients in CP with 400 mg or 600 mg imatinib resistance were randomized into the high-dose imatinib (600 mg or 800 mg) and 300 mg vamotinib groups. After imatinib therapy failure, patients could switch to vamotinib treatment. RESULTS. The trial enrolled 180 patients (89 in vamotinib and 91 in imatinib groups); interim analysis was carried out after 12 months of therapy. The primary endpoint was reached: superiority of vamotinib was demonstrated in terms of MMR rate (47.2 % vs. 12.1 % on imatinib; p < 0.001). Vamotinib is distinguished by a favorable safety profile; the number of patients with adverse events (AEs) grade 3/4 was 11 in vamotinib vs. 8 in imatinib groups. The most prevalent AE on vamotinib therapy was cutaneous toxicity; hematologic toxicity was not characteristic, no vascular occlusions were observed. CONCLUSION. The interim analysis after 12 months therapy with vamotinib showed that it holds promise for the treatment of CP CML patients with 400 mg or 600 mg imatinib resistance.