A Study of Oral Asciminib Versus Other TKIs in Adult Patients With Newly Diagnosed Ph+ CML-CP

This study is a phase III, multi-center, open-label, randomized study of oral asciminib 80 mg QD versus Investigator selected TKI (imatinib, nilotinib, dasatinib, or bosutinib) in adult patients with newly diagnosed Ph+ CML-CP. All comparator TKIs will be made available, unless not permitted by local regulations or local Health Authority or not approved for the treatment of CML in the country.

Approximately 402 patients will be randomized in a 1:1 ratio to asciminib and Investigator selected TKI to join the treatment period.

Randomization will be stratified based on the following two stratification factors:

* ELTS score (low versus intermediate versus high) * Pre-randomization selected TKI (imatinib versus 2G TKI (nilotinib or dasatinib or bosutinib)).

Prior to randomization, the Investigator, in consultation with the patient, considering the current treatment paradigm and patient characteristics and comorbidities, will make a selection of preference for imatinib or 2G TKI (nilotinib or dasatinib or bosutinib) if the patient is randomized to the comparator arm. The stratified randomization based on these two stratification factors will help to achieve a balance across the treatment arms for the possible comorbidities and baseline characteristics of patients enrolled in the study.

To further ensure that the distribution of patients, between imatinib and 2G TKIs (nilotinib or dasatinib or bosutinib), in the Investigator selected TKI arm is reflective of the use of these agents in clinical practice, the enrollment into the strata of imatinib versus 2G TKI (nilotinib or dasatinib or bosutinib) based on the pre-randomization selection of TKI will be managed by Interactive Response Technology to be approximately 50% versus 50%.

Treatment arms: The study will have 2 treatment arms:

* Arm 1: asciminib 80 mg QD under fasting conditions * Arm 2: Investigator selected TKI that will include one of the below treatments: * Imatinib 400 mg QD administered with food * Nilotinib 300 mg BID administered under fasting conditions * Dasatinib 100 mg QD administered with or without meal * Bosutinib 400 mg QD administered with food.

Apart from the treatment period described above, the present study comprises an optional Treatment-Free Remission (TFR) Period enrolling consenting participants of the treatment period (receiving asciminib or IS-TKI) who will discontinue their randomized treatment if they meet per protocol eligibility criteria. The optional TFR Period will last at least 2 years to assess the feasibility of TFR and TFR outcomes following discontinuation of their randomized treatment (asciminib or IS-TKI).