This Phase II trial is evaluating the safety and effectiveness of 3 oral drugs (Asciminib, Imatinib, Nilotinib) in patients that have been pre-treated for Chronic Myeloid Leukaemia (CML)A Phase 2, Multi-center, Open-label, Randomized Study of Oral Asciminib Added to Imatinib Versus Continued Imatinib Versus Switch to Nilotinib in Patients With CML-CP Who Have Been Previously Treated With Imatinib and Have Not Achieved Deep Molecular Response

Inclusion

1. Male or female patients ≥ 18 years of age with a confirmed diagnosis of Chronic Myeloid Leukemia in chronic phase (CML-CP).

2. Minimum of one year (12 calendar months) treatment with imatinib first line for CML-CP (patients have to be on imatinib 300mg or 400 mg QD at randomization

   For Korea only:

   (i)a minimum of one year (12 calendar months) of prior treatment with imatinib for patients with BCR-ABL levels > 0.1%, ≤ 1% IS at the time of randomization.

   (ii) a minimum of two years (24 calendar months) of prior treatment with imatinib for patients with BCR-ABL levels > 0.01%, ≤ 0.1% IS at the time of randomization.

3. BCR-ABL1 levels > 0.01% IS (International Scale) and ≤ 1% IS at the time of randomization as confirmed with a central assessment at screening; patients must not have achieved deep molecular response (MR4 IS) confirmed by 2 consecutive tests at any time during prior imatinib treatment. An isolated, single test result with BCR-ABL1 levels < 0.01 % (MR4 IS) is allowed, however, it should not have been observed within the 9 months prior to randomization

4. Patient must meet the following laboratory values before randomization:

   • Absolute Neutrophil Count ≥ 1.5 x 10E9/L
   • Platelets ≥ 75 x 10E9/L
   • Hemoglobin ≥ 9 g/dL
   • Serum creatinine < 1.5 mg/dL
   • Total bilirubin ≤ 1.5 x ULN (Upper Limit of Normal) except for patients with Gilbert's syndrome who may only be included with total bilirubin ≤ 3.0 x ULN
   • Aspartate transaminase (AST) ≤ 3.0 x ULN
   • Alanine transaminase (ALT) ≤ 3.0 x ULN
   • Alkaline phosphatase ≤ 2.5 x ULN
   • Serum lipase ≤ 1.5 x ULN
5. Patients must have the following laboratory values ≥ Lower Limit of Normal or corrected to within normal limits with supplements prior to randomization: potassium increase of up to 6.0 mmol/L is acceptable if associated with creatinine clearance within normal limits ; calcium increase of up to 12.5 mg/dl or 3.1 mmol/L is acceptable if associated with creatinine clearance* within normal limits) ; magnesium increase up to 3.0 mg/dL or 1.23 mmol/L if associated with creatinine clearance within normal limits.