Open-label Study of Asciminib for CML-CP or CML-AP Patients With T315I Mutation Who Are Resistant, Intolerant or Ineligible to Ponatinib.

Inclusion Criteria:

• Signed informed consent must be obtained prior to participation in the study.

• Male or female participants with a diagnosis of CML-CP or CML-AP ≥ 18 years of age.

• Patients with CML-CP or CML-AP with history of documented T315I mutation after atleast one TKI and are resistant, intolerant, or ineligible to ponatinib (accordingto Investigator judgment)

• Not already treated with asciminib or another any allosteric TKI

• Failure (adapted from the 2020 & 2013 ELN Guidelines) or intolerance to Ponatinib atthe time of Screening.

• Ineligible to ponatinib according to Investigator (based on EU ponatinib SmPC)

• Evidence of typical BCR::ABL1 transcript or atypical transcripts at the time ofScreening which are amenable to standardized or non-standardized RQ-PCRquantification.

Exclusion Criteria:

• Previous hematopoietic allogeneic stem-cell transplantation

• Cardiac or cardiac repolarization abnormality

• Severe and/or uncontrolled concurrent medical disease that in the opinion of theInvestigator could cause unacceptable safety risks or compromise compliance with theprotocol (e.g. uncontrolled diabetes, active or uncontrolled infection, pulmonaryhypertension)

• History of clinical acute pancreatitis within 1 year of study entry or past medicalhistory of chronic pancreatitis (except if ponatinib-induced and completely resolvedat time of Screening)

• History of acute or chronic liver disease (i.e., cirrhosis; liver impairment)

• Known presence of significant congenital or acquired bleeding disorder unrelated tocancer

• History of other active malignancy within 3 years prior to study entry with theexception of previous or concomitant basal cell skin cancer and previous carcinomain situ treated curatively

• Known history of Human Immunodeficiency Virus (HIV), chronic Hepatitis B Virus (HBV), or chronic Hepatitis C Virus (HCV) infection. Testing for Hepatitis B surfaceantigen (HBs Ag) and Hepatitis B core antibody (HBcAb / anti HBc) will be performedat Screening

• Impairment of gastrointestinal (GI) function or GI disease that may significantlyalter the absorption of study drug (e.g. ulcerative disease, uncontrolled nausea,vomiting, diarrhea, malabsorption syndrome, small bowel resection, or gastric bypasssurgery)

• Treatment with medications that meet one of the following criteria and that cannotbe discontinued at least one week prior to the start of treatment with studytreatment:

• Moderate or strong inducers of CYP3A

• Moderate or strong inhibitors of CYP3A

• Pregnant or nursing (lactating) women

• Women of child-bearing potential

• Compound mutant T315I resistant to asciminib monotherapy (polyclonal ABL1 mutationsincluding T315I can be enrolled) Other protocol-defined inclusion/exclusion criteriamay apply.