Multinational phase 1-2 trial of vodobatinib for Ph-positive CML after multiple lines of previous therapy

Vodobatinib is a novel selective BCR::ABL1 tyrosine kinase inhibitor (TKI). A phase 1-2 trial at 28 center in ten countries evaluated oral vodobatinib in patients with advanced Philadelphia chromosome-positive chronic myeloid leukemia (CML), who previously received at least three TKIs, including ponatinib and asciminib. The maximum tolerated vodobatinib dose was 204 mg once daily. Treatment-emergent adverse events occurred in 94% of patients, and grade 3 or higher TRAEs occurred in 60%. One of 78 patients died of a treatment-related cause. Major cytogenetic response was seen in 70% of patients with chronic-phase CML, whereas major hematological response was seen in 86% of patients with accelerated-phase CML and in two of four patients with blast-phase CML. The authors conclude that vodobatinib showed clinically meaningful activity and tolerable safety among patients with advanced CML who previously received multiple TKIs, including ponatinib and asciminib.