Chronic Myeloid Leukemia Coverage from Every Angle

Novel TKI Under Study in Resistant Chronic-Phase CML

By: Celeste L. Dixon
Posted: Wednesday, January 13, 2021

The results of an exploratory phase I dose-escalation study revealed that vodobatinib, a novel third-generation tyrosine kinase inhibitor (TKI), is active in certain patients with chronic-phase chronic myeloid leukemia (CML) that has failed to respond to at least three TKIs (or fewer than three TKIs if patients are not eligible for other third-generation TKIs). Vodobatinib appears to be effective against wild-type and mutated BCR-ABL1, with limited off-target activity, reported Jorge E. Cortes, MD, of Augusta University’s Georgia Cancer Center, and colleagues during the 2020 American Society of Hematology (ASH) Annual Meeting and Exposition (Abstract 652).

The agent merits further study, said the team, in part because its efficacy was comparable and promising in both ponatinib-treated (50% complete cytogenic response) and ponatinib-naive (67% complete cytogenic response) groups. The researchers evaluated nine escalating doses of once-daily oral vodobatinib in 28-day cycles; the primary objectives were to determine the maximum tolerated dose or recommended phase II dose as well as safety. Evaluating antileukemic activity was a secondary objective.

A total of 31 patients received vodobatinib at doses of 12 mg to 240 mg, with 16 and 15 patients in the ponatinib-treated and ponatinib-naive cohorts, respectively. At 240 mg, two dose-limiting toxicities were reported, so the next-lowest level, 204 mg, was established as the maximum tolerated dose with a favorable safety profile.

With treatment continuing until unacceptable toxicity, disease progression, consent withdrawal, or death, the median duration of treatment was 17.3 months (range, 0.6–36 months) and 14.8 months (range, 0.5–42 months) in the ponatinib-treated and -naive groups, respectively. A total of 11 and 10 responding patients in those groups, respectively, remain on treatment. The most commonly reported treatment-emergent adverse events of all grades included nausea (25%) and diarrhea (25%) in ponatinib-treated patients and myalgia (33%) and back pain (27%) in the ponatinib-naive group.

Disclosure: The study authors’ disclosure information can be found at

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