CML-395 Efficacy and Safety Results From ASCEMBL, a Phase III Study of Asciminib vs. Bosutinib in Patients With Chronic Myeloid Leukemia in Chronic Phase (CML-CP) After ≥2 Prior Tyrosine Kinase Inhibitors (TKIs): Week 96 Update

Abstract

Asciminib is the first BCR::ABL1 inhibitor to Specifically Target the ABL Myristoyl Pocket (STAMP). In the ASCEMBL primary analysis, among patients with CML-CP after ≥2 prior TKIs, asciminib resulted in improved major molecular response (MMR, 25.5% vs. 13.2%) at week 24 and fewer grade ≥3 adverse events (AEs) or AEs leading to treatment discontinuations compared with bosutinib. After a median follow-up of 2.3 years, we report updated efficacy and safety results (data cutoff: October 6, 2021). To compare the MMR rate at week 96 with asciminib vs. bosutinib. A phase III, multicenter, open-label study of adults with CML-CP after ≥2 prior TKIs randomized 2:1 to asciminib 40 mg twice daily or bosutinib 500 mg once daily and stratified by baseline major cytogenetic response (MCyR). In total, 233 patients were randomized to receive asciminib (n=157) or bosutinib (n=76). At data cutoff, treatment was ongoing in 84 (53.5%) and 15 (19.7%) patients, respectively; the most common reason for discontinuation was lack of efficacy in 38 (24.2%) and 27 (35.5%) patients, respectively. The key secondary objective was met; MMR rate at week 96 was higher with asciminib (37.6%) than with bosutinib (15.8%). The difference after adjusting for MCyR was 21.7% (95% CI, 10.5%-33.0%; 2-sided P=.001). At week 96, more patients receiving asciminib than bosutinib had BCR::ABL1IS ≤1% (45.1% vs. 19.4%). Responses were durable, with a probabilities (95% CI) of maintaining MMR and BCR::ABL1IS ≤1% for ≥72 weeks of 96.7% (87.4%-99.2%) and 94.6% (86.2%-97.9%), respectively, with asciminib and 92.9% (59.1%-99.0%) and 95.0% (69.5%-99.3%), respectively, with bosutinib. Median time to treatment failure was 24 months with asciminib and 6 months with bosutinib. Asciminib had longer duration of exposure (103.1 vs. 30.5 weeks) but fewer AEs leading to treatment discontinuation (7.7% vs. 26.3%) than bosutinib. After >2 years of follow-up, asciminib demonstrated durable responses by continuing to show superior efficacy and better safety/tolerability vs. bosutinib. MMR more than doubled with asciminib over bosutinib, and the difference in MMR rates increased between the 2 arms from 12.2% at week 24 to 21.7% at week 96. These results support the use of asciminib as a new CML therapy.