The median duration of exposure was 68.4 wk (range, 2-175 wk) and median dose intensity was 399.0 mg/day (range, 188-400 mg/day).
Of pts still on treatment, 31/35 (88.6%) received treatment for > 48 wk. At the data cutoff, treatment was ongoing in 35/52 pts (67.3%) 17 (32.7%) discontinued treatment, a majority of whom (10 ) discontinued due to physician's decision, mainly for unsatisfactory response (Table 1). Results: A total of 52 pts with T315I received asciminib 200 mg BID. Here, we report updated efficacy and safety results in pts with T315I who received 200 mg BID (data cutoff: April 2, 2020). Pts with T315I were assigned to varying dose levels in phase 1, and 200 mg twice daily (BID) was selected for cohort expansion. Pts with uncontrolled cardiovascular conditions were excluded. Methods: This phase 1 study enrolled adults with CML in chronic phase (CP) or accelerated phase (AP) R/I ≥ 2 TKIs pts with T315I were eligible after receiving ≥ 1 TKI if no other effective therapy was available. Asciminib demonstrated clinical activity in heavily pretreated CML pts with or without mutations, with promising efficacy in pts with T315I, including those resistant to/intolerant of (R/I) PON. Asciminib has a distinct mechanism of action and is the first-in-class STAMP (Specifically Targeting the ABL Myristoyl Pocket) inhibitor.
PON use, however, is limited in many patients by its safety profile. The T315I mutation confers resistance to all approved ATP-competitive TKIs except ponatinib (PON) and is associated with significantly worse clinical outcomes. However, resistance to treatment driven by point mutations in the ABL kinase domain, particularly the T315I mutation, represents a clinical challenge. Introduction: Tyrosine kinase inhibitors (TKIs) are an effective therapy for pts with CML.
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