PEARL Study: PotEntial of Asciminib in the eaRly Treatment of CML

Inclusion Criteria:

• Cytogenetic and molecular confirmed diagnosis of Ph+ and BCR::ABL1+ CML

• Age ≥ 18 years

• Early chronic phase, less than 3 months from diagnosis

• Evidence at the time of study entry of typical BCR::ABL1 RNA transcripts e13a2 ore14a2 (b2a2 or b3a2), which are required for BCR::ABL1 international scale reporting

• Prior treatment with any TKI for 30 days or less; prior treatment with hydroxyureaor anagrelide is allowed

• ECOG performance status of 0, 1 or 2

• Adequate end organ function as defined by Total bilirubin ≤ 1.5 x ULN except forpatients with Gilbert's syndrome who may only be included if total bilirubin ≤ 3.0 xULN or direct bilirubin ≤ 1.5 x ULN Aspartate transaminase (AST) ≤ 3.0 x ULN Alaninetransaminase (ALT) ≤ 3.0 x ULN Serum amylase ≤ ULN Serum lipase ≤ ULN Alkalinephosphatase ≤ 2.5 x ULN, unless considered tumor related Creatinine clearance > 50ml/min using Cockcroft-Gault formula

• Signed written informed consent according to ICH/EU/GCP and national local lawsprior to any study procedure

• An effective form of contraception with their sexual partners from enrolment through 30 days after the end of treatment

Exclusion Criteria:

• CML in blast phase (BP) or in second chronic phase after previous BP, according toWHO criteria

• Previous treatment with TKIs for more than 30 days

• Refusal or impossibility to give an informed consent

• History or current diagnosis of cardiac disease indicating significant risk ofsafety for patients participating in the study such as uncontrolled or significantcardiac disease, including any of the following: recent myocardial infarction (within last 6 months), uncontrolled congestive heart failure, unstable angina (within last 6 months), clinically significant (symptomatic) cardiac arrhythmias (e.g., sustained ventricular tachycardia, and clinically significant second or thirddegree AV block without a pacemaker).

• 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)

• History of acute pancreatitis within 1 year of study entry or past medical historyof chronic pancreatitis

• History of acute or chronic liver disease

• History of other active malignancy within 2 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), Hepatitis B (HBV), or HepatitisC (HCV) infection. Testing for Hepatitis B surface antigen (HBs Ag) and Hepatitis Bcore antibody (HBc Ab / anti HBc) will be performed at study entry

• 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)

• Pregnant or lactating women, where pregnancy is defined as the state of a femaleafter conception and until the termination of gestation, confirmed by a positive hCGlaboratory test.

• Women of child-bearing potential, unless they are using highly effective methods ofcontraception during dosing and for 30 days after the end of treatment