DISCUSSION
CML
CML
ASCEMBL is the first randomized, controlled study in patients with CML‐CP who have been previously treated with TKIs. In the primary analysis of the overall study population, asciminib demonstrated a statistically significant clinical benefit versus bosutinib, meeting the primary study endpoint with an almost two times higher 24‐week MMR rate in asciminib‐randomized patients vs bosutinib‐randomized patients.The present study is the first report providing evidence on the efficacy and safety of asciminib in patients from Japan. In Japanese patients, MMR rates achieved with asciminib at week 24 (30.8%) were comparable to those observed with asciminib in the overall ASCEMBL study population (25.5%; Table Week 24 efficacy and safety in Japanese patients and in all patients randomized to asciminib in the ASCEMBL studyAbbreviations: CCyR, complete cytogenetic response; IS, international scale; MMR, major molecular response; MRAmong patients without CCyR at baseline (Japan In the present subgroup analysis, no patient receiving bosutinib achieved MMR, CCyR, or In the overall ASCEMBL study population, the difference in MMR rates at week 24 between asciminib and bosutinib was 12.2%. Of note, a higher MMR rate was achieved with asciminib vs bosutinib, irrespective of prior lines of therapy, and in patients who discontinued their previous TKI treatment due to efficacy reasons.No comparative conclusions for asciminib versus bosutinib can be drawn from this Japanese subgroup analysis due to the small number of bosutinib patients.The safety profile of asciminib observed in this Japanese subgroup is comparable to that observed in the overall ASCEMBL study population and is also in line with that observed in the phase 1 study.With ATP‐competitive inhibitors such as imatinib and second‐generation TKIs, many AEs are due to off‐target activities as these agents are not specific for ABL1, ABL2, and BCR‐ABL1.In ASCEMBL, the starting dose of bosutinib was 500 mg qd, which is the approved dose for Japanese patients with resistant and/or intolerant CML.