A phase III, multi-center, open-label, randomized study of oral asciminib versus Investigator selected TKI in patients with newly diagnosed Philadelphia Chromosome Positive Chronic Myelogenous Leukemia in Chronic Phase

INTERVENTION: Product Name: Asciminib Product Code: ABL001 Pharmaceutical Form: Film‐coated tablet INN or Proposed INN: ASCIMINIB Current Sponsor code: ABL001 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 40‐ Trade Name: Bosulif Product Name: Bosulif Pharmaceutical Form: Film‐coated tablet INN or Proposed INN: BOSUTINIB CAS Number: 380843‐75‐4 Other descriptive name: Bosutinib Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 400‐ Trade Name: Glivec Product Name: Glivec Product Code: STI571 Pharmaceutical Form: Film‐coated tablet INN or Proposed INN: imatinib CAS Number: 152459‐95‐5 Other descriptive name: IMATINIB Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 400‐ Trade Name: Tasigna Product Name: Tasigna Product Code: AMN107 Pharmaceutical Form: Capsule, hard INN or Proposed INN: NILOTINIB CAS Number: 641571‐10‐0 Other descriptive name: Nilotinib Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 150‐ Trade Name: Sprycel Product Name: Sprycel Pharmaceutical Form: Film‐coated tablet INN or Proposed INN: Dasatinib CAS Number: 302962‐49‐8 Other descriptive name: dasatinib Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 100‐ Trade Name: Bosulif Product Name: Bosulif Pharmaceutical Form: Film‐coated tablet INN or Proposed INN: BOSUTINIB CAS Number: 380843‐75‐4 Other descriptive name: Bosutinib Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 100‐ Trade Name: Glivec Product Name: Glivec Product Code: STI571 Pharmaceutical Form: Film‐coated tablet INN or Proposed INN: imatinib CAS Number: 152459‐95‐5 Other descriptive name: IMATINIB Concentration unit: mg milligram(s) CONDITION: Chronic Myelogenous Leukemia in chronic phase (CML‐CP) in newly diagnosed patients ; MedDRA version: 21.0 Level: LLT Classification code 10009012 Term: Chronic myelogenous leukemia System Organ Class: 100000004864 Therapeutic area: Diseases [C] ‐ Cancer [C04] SECONDARY OUTCOME: Secondary end point(s): 1. Major Molecular response (MMR) at Week 96 (Yes/No) ; 2. Time to discontinuation of study treatment due to Adverse Events (TTDAE) ; 3. Other protocol‐defined secondary endpoints will apply; please see protocol for a detailed list of all secondary endpoints Timepoint(s) of evaluation of this end point: 1. 96 weeks ; 2. 96 weeks after last patient first dose ; 3. Other protocol‐defined timepoints of evaluation will apply; please see protocol for a full list of timepoints for all endpoints INCLUSION CRITERIA: Participants eligible for inclusion in this study must meet all of the following criteria: 1. Male or female patients = 18 years of age. 2. Patients with CML‐CP within 3 months of diagnosis. 3. Diagnosis of CML‐CP with cytogenetic confirmation of Philadelphia chromosome of (9;22) translocations (presence of BCR‐ABL1 in a review of a minimum 20 metaphases is required). ‐ Documented chronic phase CML will meet all the below criteria Hochhaus et al 2020: •< 15% blasts in peripheral blood and bone marrow, •< 30% blasts plus promyelocytes in peripheral blood and bone marrow, •< 20% basophils in the peripheral blood, •Platelet count = 100 x 109/L (= 100,000/mm3), •No evidence of extramedullary leukemic involvement, with the exception of hepatosplenomegaly. 4. Eastern Cooperative Oncology Group (ECOG) performance status of 0, or 1. 5. Adequate end organ function as defined by: • Total bilirubin PRIMARY OUTCOME: Main Objective: 1. To compare the efficacy of asciminib versus Investigator selected TKI, with respect to proportion of patients in Major Molecular Response (MMR) at Week 48.; 2. To compare the efficacy of asciminib versus Investigator selected TKI, within the stratum of patients with imatinib as the pre‐randomization selected TKI, with respect to proportion of patients in MMR at Week 48.; Primary end point(s): Major Molecular response (MMR) at Week 48 (Yes/No) ; Secondary Objective: 1. To compare the efficacy of asciminib versus Investigator selected TKI, with respect to proportion of patients in MMR at Week 96.; 2. To compare the efficacy of asciminib versus Investigator selected TKI, within the stratum of patients with imatinib as the pre‐randomization selected TKI, with respect to proportion of patients in MMR at Week 96; 3. To characterize the safety and tolerability profile of asciminib versus 2G TKIs: nilotinib, dasatinib or bosutinib; 4. Other protocol‐defined secondary objectives will apply; please see the protocol for a detailed list of all secondary objectives; ; Timepoint(s) of evaluation of this end point: 48 weeks