INTRODUCTION: Management of chronic phase chronic myeloid leukemia (CML-CP) was revolutionized with the development of tyrosine kinase inhibitors (TKIs). Imatinib (first generation), dasatinib, nilotinib and bosutinib (second generation) and ponatinib (third generation) are the five approved TKIs that inhibit BCR::ABL1 by binding to the ATP binding site of ABL1. About half of the resistance to TKIs develops through acquisition of mutations in the ATP binding site, including T315I. Hence, a novel TKI with a distinct mechanism of action, that inhibits bcr-abl1 by specifically targeting the ABL1 myristoyl pocket (STAMP inhibitor) was developed. AREAS COVERED: Asciminib was first approved for treatment of CML-CP in the third line setting or beyond and in patients with T315I mutation in October, 2021. More recently, in October, 2024, asciminib was approved for newly diagnosed CML-CP based on ASC4FIRST data showing MMR rate of 67.7% in the asciminib arm compared to 49% in the investigator choice TKI arm ( EXPERT OPINION: Due to its mechanism of action, asciminib has fewer off target effects, resulting in an improved safety and tolerability profile.