Asciminib, a Specific Allosteric BCR-ABL1 Inhibitor, in Patients with Chronic Myeloid Leukemia Carrying the T315I Mutation in a Phase 1 Trial

We report results from the largest cohort: pts with confirmed T315I mut at screening (tested locally by Sanger sequencing) and treated with asciminib 200 mg BID, which showed the most robust efficacy (data cutoff: April 30, 2018).At the data cutoff, treatment was ongoing in 23/24 pts (95.8%) (Table); 1 pt (4.2%) had ended treatment. Median duration of follow-up and asciminib exposure were both 28.5 wk (range, 0.1-74.7 wk). Most pts had received multiple prior TKIs, and PON was the most recent TKI for 12/24 (50.0%). Pts who were PON naive had underlying conditions, such as CV risk factors. Eight of 24 pts achieved MMR by 24 wk; 1 achieved MMR after 24 wk. Ten of 24 pts had BCR-ABL1 < 10% on the International Scale (IS) at screening and ≥ 1 postbaseline evaluation; 6/10 (60%) achieved a ≥ 1-log reduction in BCR-ABL1IS by 24 wk. Among PON-naive and PON-R/I pts, 5/11 and 3/13, respectively, achieved MMR by 24 wk (Figure). One PON-R/I pt with isolated T315I at screening lost MMR 3 mo after achieving it (prior TKIs: imatinib, dasatinib, and PON). Analysis of 200 mg BID pharmacokinetic data is planned.A total of 20/24 pts (83.3%) experienced any-grade AEs (grade 3/4, 8/24 [33.3%]); the most frequent any-grade AEs were arthralgia, fatigue, lipase increased, and nausea (4/24 [16.7%] each). Any-grade AEs suspected to be study drug related were reported in 15/24 pts (62.5%; grade 3/4, 3/24 [12.5%]) and most frequently included arthralgia and nausea (3/24 [12.5%] each). One pt e...
Source: Blood - Category: Hematology Authors: Tags: 632. Chronic Myeloid Leukemia: Therapy: TFR Failure, Resistance, and New Drug Development Source Type: research