Phase-3 study of vamotinib (PF-114) versus high-dose imatinib

Abstract Background Vamotinib (PF-114), an oral tyrosine kinase-inhibitor (TKI) is active against wild-type and BCR::ABL1 variants. Whether it is safer and more effective compared with high-dose imatinib in people with chronic phase chronic myeloid leukaemia (CML) failing conventional dose imatinib is unknown. Method Multi-centre open-label phase-3 trial with endpoints of safety and 1-year major molecular response (MMR). Other endpoints are rates of BCR::ABL1IS < 1% (MR2), MR4 and MR4.5. Subjects with imatinib-resistant BCR::ABL1 variantswere excluded. Results 180 subject (vamotinib, 300 mg; N = 89; imatinib; 800 mg; N = 91) were enrolled. 117 were men. Median age was 44 years (Range 18-75 years). Median CML duration pre-study was 4 years (Range, < 1-24 years). 65 subjects (73%) in the vamotinib cohort and 65 (71%) in the imatinib cohort had pre-study BCR::ABL1 ≥ 10%. Rate of achieving 1-year MMR with vamotinib was 47% compared with imatinib, 12% ( p < 0.001). Rates of other endpoints were also higher with vamotinib. There were no significant differences frequency of adverse events (AEs). Skin toxicity was the most common AE for vamotinib. Conclusion Vamotinib, 300 mg, is as safe as imatinib, 800 mg, but more effective in achieving 1-year MMR. The study is ongoing.