PF-114 in Patients Failing Prior Tyrosine Kinase-Inhibitor Therapy Including BCR::ABL1T315I (original) (raw)

Blood

Abstract

Background: Not everyone with CML responds optimally to TKI-therapy, especially those with BCR::ABL1T315I. PF-114 is a 4 th-generation oral tyrosine kinase-inhibitor (TKI) active against wild-type and mutated BCR::ABL1 isoforms including BCR::ABL1T315I. We present final results of a phase-1 study (NCT02885766). Methods: 3+3 dose-escalation study to determine maximum tolerated dose (MTD) and dose-limiting toxicity (DLT). Secondary objectives included safety and efficacy based on haematological, cytogenetic and molecular response criteria. Adverse events (AEs) were graded using NCI-CTCAE v4.03. Results: 51 subjects (5 with accelerated phase CML, 46 - with chronic CML), 23 males, were studied. Daily doses were 50-600 mg/d given once daily continuously. Median age was 50 y (range, 29-82 y). Median CML duration pre-study was 10 y (range, 0.3-23 y). 16 subjects had BCR::ABL1T315I. 25 subjects received ≥ 3 prior TKIs. Median follow-up was ≥ 31 mo and median exposure, 6 mo (range, 0.4-52). ...

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