Vodobatinib Promising for Multiple-TK-Inhibitor-Resistant Philadelphia chromosome-positive CML

Pooled analysis for a phase 1/2 clinical trial supports vodobatinib, a novel selective BCR–ABL1 tyrosine kinase inhibitor (TKI), as a viable option for Philadelphia chromosome-positive chronic myeloid leukemia (CML) that has withstood prior TKI interventions. The research team that performed this analysis recently published their findings in The Lancet Haematology.

“Vodobatinib has shown in this analysis very encouraging and promising results for patients with resistance or intolerance to multiple prior therapies. These include patients previously treated with ponatinib, a particularly difficult to treat patient population,” first author of the analysis Jorge Cortes, MD, of Georgia Cancer Center, Augusta University, explained in remarks forwarded to Blood Cancers Today.

In this open-label, international phase 1/2 trial, the phase 1 segment enrolled adults with Philadelphia chromosome-positive CML or acute lymphoblastic leukemia who had already received at least three TKIs or had no other viable treatment options. The patients enrolled in the phase 2 segment had disease against which response had been lost on at least three prior TKIs and ponatinib. In both segments patients with Thr315Ile mutation were excluded.

The safety and efficacy analysis set included 78 patients; the phase 1 segment enrolled 58 and the phase 2 segment enrolled 20. In this set the median patient age was 59 years and 55% of patients were men. Eighty-five percent of the set had chronic-phase CML, 10% had accelerated-phase CML, and 5% had blast-phase CML.

Patients self-administered 12mg to 240mg oral vodobatinib once daily for each 28-day treatment cycle for up to 60 months. The median follow-up was 22.3 months.

Among 63 patients with chronic-phase CML in the analysis set, 70% had a major cytogenic response. In the phase 2 study, 75% of patients with chronic phase CML had a major cytogenic response.

In the analysis set, 86% of patients with accelerated-phase CML had a major hematological response, with a median duration of 17.8 months. In the phase 2 study segment, 100% of evaluable patients with accelerated-phase CML had a major hematological response.

In the analysis set, 50% of patients with blast-phase CML had a major hematological response, with a median duration of 6.2 months. The phase 2 segment had no patients with blast-phase CML.

Regarding safety results, 94% of the analysis set had at least one treatment-emergent adverse event (TEAE), most of which were grade 2 or less severe hematological or gastrointestinal events. Sixty percent of the set had grade 3 or worse severity TEAEs. These included thrombocytopenia which affected 18% of the set, neutropenia in 13%, anemia in 12%, and increased lipase in 10%.

“The safety profile was very favorable suggesting that vodobatinib could be a valuable addition to our armamentarium in CML,” Dr. Cortes summarized in his remarks.

During the study, there were seven patient deaths in the analysis set, one of which the clinical investigator deemed treatment related.

In their published findings, Dr. Cortes and his coauthors noted that the phase 2 segment of the study was statistically underpowered. Therefore, they consider a phase 3, randomized, controlled trial necessary, as well as an investigation of vodobatinib within earlier CML treatment settings.

The phase 1/2 clinical trial was funded by Sun Pharma Advanced Research Company.

Reference

Cortes JE, Kim DW, Saikia T, et al. Vodobatinib for patients with Philadelphia chromosome-positive chronic myeloid leukaemia resistant or intolerant to multiple lines of previous therapy: an open-label, multicentre, phase 1/2 trial. Lancet Haematol. 2025;12(3):e201-e213. doi:10.1016/S2352-3026(24)00354-5