• Age ≥ 18 years.

• Diagnosis of Ph-positive (by cytogenetics or FISH) or BCR-ABL-positive (by PCR) CML in chronic phase and have received one prior line of therapy with a TKI.

• History of treatment failure defined as either:

‣ BCR::ABL1 \>0.1% for patients with intolerance to first-line TKI

⁃ Less than complete hematologic response (CHR) at ≥3 months

⁃ No partial cytogenetic response at ≥3 months

⁃ BCR::ABL1 ≥ 10% at if 3-6 months

⁃ BCR::ABL1 ≥ 1% at ≥6 months

⁃ Loss of CCyR or development of mutations or other clonal chromosomal abnormalities at any time during TKI treatment

• ECOG performance status ≤ 2.

• Adequate end organ function within 12 days before the first dose of asciminib treatment. Patients with mild to moderate renal and hepatic impairment are eligible if:

‣ Total bilirubin ≤ 3.0 x ULN without AST/ALT increase

⁃ Aspartate transaminase (AST) ≤ 5.0 x ULN

⁃ Alanine transaminase (ALT) ≤ 5.0 x ULN

⁃ Serum lipase ≤ 1.5 x ULN. For serum lipase \> ULN and ≤ 1.5 x ULN, value should be considered not clinically significant and not associated with risk factors for acute pancreatitis

⁃ Alkaline phosphatase ≤ 2.5 x ULN

⁃ Creatinine clearance ≥ 30 mL/min as calculated using Cockcroft-Gault formula

• The effects of Asciminib on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Women of child-bearing potential must agree to use highly effective methods of contraception during dosing and for 30 days after study treatment. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Allowable methods of birth control:

‣ Total abstinence (when this is in line with the preferred and usual lifestyle of the subject). Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.

⁃ Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy), total hysterectomy, or tubal ligation at least six weeks before the start of study treatment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment.

⁃ Male sterilization (at least 6 months prior to screening). The vasectomized male partner should be the sole partner for that subject.

⁃ Use of oral, injected or implanted hormonal methods of contraception or placement of an intrauterine device (IUD) or intrauterine system (IUS), or other forms of hormonal contraception that have comparable efficacy (failure rate \<1%), for example hormone vaginal ring or transdermal hormone contraception.

⁃ Sexually active males must use a condom during intercourse while taking the drug and for 30 days after stopping treatment and should not father a child in this period. A condom is required to be used also by vasectomized men in order to prevent delivery of the drug via seminal fluid.