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Phase I evaluation of XL019, an oral, potent, and selective JAK2 inhibitor.

ABSTRACT: This phase I study evaluated selective JAK2 inhibitor XL019 in 30 patients with myelofibrosis. The initial dose cohorts were 100, 200, and 300 mg orally on days 1-21 of a 28-day cycle. Central and/or peripheral neurotoxicity developed in all patients. Subsequently, patients were treated on lower doses; neurotoxicity was again observed, leading to study termination. Peripheral neuropathy resolved in 50%, and central neurotoxicity in all patients within months after therapy cessation. Myelosuppression was minimal. The terminal half-life of XL019 was approximately 21 h, with steady state reached by Day 8. International Working Group defined responses were seen in three (10%) patients.

SUBMITTER: Verstovsek S

PROVIDER: S-EPMC4414320 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature

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Phase I evaluation of XL019, an oral, potent, and selective JAK2 inhibitor.

Verstovsek Srdan S Tam Constantine S CS Wadleigh Martha M Sokol Lubomir L Smith Catherine C CC Bui Lynne A LA Song Chunyan C Clary Douglas O DO Olszynski Patrycja P Cortes Jorge J Kantarjian Hagop H Shah Neil P NP

Leukemia research 20131211 3

This phase I study evaluated selective JAK2 inhibitor XL019 in 30 patients with myelofibrosis. The initial dose cohorts were 100, 200, and 300 mg orally on days 1-21 of a 28-day cycle. Central and/or peripheral neurotoxicity developed in all patients. Subsequently, patients were treated on lower doses; neurotoxicity was again observed, leading to study termination. Peripheral neuropathy resolved in 50%, and central neurotoxicity in all patients within months after therapy cessation. Myelosuppres ...[more]

PMID: 24374145

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Remibrutinib (LOU064): A selective potent oral BTK inhibitor with promising clinical safety and pharmacodynamics in a randomized phase I trial.

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Project description: Not available

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