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

Molecular response is assessed using BCR-ABL transcript levels measured by realtime quantitative polymerase chain reaction. MMR is defined as a ratio BCR-ABL/ABL ≤0.1% on the international scale (ie, at least 3 log reduction from a standardized baseline value).

TTDAE is defined as the time from the date of first dose of study treatment to the date of discontinuation of study treatment due to Adverse Event (AE). For patients ongoing without study treatment discontinuation, on or prior to the analysis cut-off date, the time will be censored at the at the analysis cut-off date.

Molecular response is assessed using BCR-ABL transcript levels measured by realtime quantitative polymerase chain reaction. MMR is defined as a ratio BCR-ABL/ABL ≤0.1% on the international scale (ie, at least 3 log reduction from a standardized baseline value).

Molecular response is assessed using BCR-ABL transcript levels measured by realtime quantitative polymerase chain reaction. MMR is defined as a ratio BCR-ABL/ABL ≤0.1% on the international scale (ie, at least 3 log reduction from a standardized baseline value).

Molecular response is assessed using BCR-ABL transcript levels measured by realtime quantitative polymerase chain reaction. MR4.0 is defined as a ratio BCR-ABL/ABL ≤0.01% on the international scale (ie, at least 4 log reduction from a standardized baseline value).

Molecular response is assessed using BCR-ABL transcript levels measured by realtime quantitative polymerase chain reaction. MR4.5 is defined as a ratio BCR-ABL/ABL ≤0.0032% on the international scale (ie, at least 4.5 log reduction from a standardized baseline value).

Molecular response is assessed using BCR-ABL transcript levels measured by realtime quantitative polymerase chain reaction. MR4.0 is defined as a ratio BCR-ABL/ABL ≤0.01% on the international scale (ie, at least 4 log reduction from a standardized baseline value).

Molecular response is assessed using BCR-ABL transcript levels measured by realtime quantitative polymerase chain reaction. MR4.5 is defined as a ratio BCR-ABL/ABL ≤0.0032% on the international scale (ie, at least 4.5 log reduction from a standardized baseline value).

Hematologic response will be assessed by CBC and physical examination at each visit.

Complete Hematological Response (CHR) will be defined as all of the following present for ≥ 4 weeks:

white blood cell(s) (WBC) count < 10 x 10^9/L PLT count < 450 x 10^9/L Basophils < 5% No blasts and promyelocytes in peripheral blood Myelocytes + metamyelocytes < 5% in peripheral blood No evidence of extramedullary disease, including spleen and liver

Hematologic response will be assessed by CBC and physical examination at each visit.

Complete Hematological Response (CHR) will be defined as all of the following present for ≥ 4 weeks:

white blood cell(s) (WBC) count < 10 x 10^9/L PLT count < 450 x 10^9/L Basophils < 5% No blasts and promyelocytes in peripheral blood Myelocytes + metamyelocytes < 5% in peripheral blood No evidence of extramedullary disease, including spleen and liver

The CCyR response status was to be based on bone marrow assessment. Bone marrow examination for cytogenetic assessment was to be performed locally by the Investigator at baseline for all participants. Thereafter, during the course of the study, cytogenetic assessment was not mandatory and only performed if clinically indicated.

Duration of MMR is defined as the time between the date of the first documented achievement of MMR and the earliest date of loss of MMR, treatment failure, progression to Accelerated Phase/Blast Crisis, or CML-related death

Duration of MR4.0 is defined as the time between the date of the first documented achievement of MR4.0 and the earliest date of loss of MR4.0, treatment failure, progression to Accelerated Phase/Blast Crisis, or CML-related death

Duration of MR4.5 is defined as the time between the date of the first documented achievement of MR4.5 and the earliest date of loss of MR4.5, treatment failure, progression to Accelerated Phase/Blast Crisis, or CML-related death

Time to first MMR is defined as the time from the date of randomization to the date of the first documented occurrence of MMR. Time will be censored at the last molecular assessment date while on treatment, or the End Of Treatment (whichever comes first) for patients who have not experienced MMR.

Time to first MR4.0 is defined as the time from the date of randomization to the date of the first documented occurrence of MR4.0. Time will be censored at the last molecular assessment date while on treatment, or the End Of Treatment (whichever comes first) for patients who have not experienced MR4.0.

Time to first MR4.5 is defined as the time from the date of randomization to the date of the first documented occurrence of MR4.5. Time will be censored at the last molecular assessment date while on treatment, or the End Of Treatment (whichever comes first) for patients who have not experienced MR4.5.

Molecular response is assessed using BCR-ABL transcript levels measured by realtime quantitative polymerase chain reaction.

Molecular response is assessed using BCR-ABL transcript levels measured by realtime quantitative polymerase chain reaction.

TTF is defined as the time from date of randomization to the first/earliest documented date of any of the following events: treatment failure as per ELN, Confirmed loss of MMR while on study treatment, discontinuation from study treatment due to any reason

For patients that have not experienced an event prior to or at the analysis cut-off date, the time will be censored at the last study assessment date while on treatment, or the EOT (whichever comes first) .

FFS is defined as the time from the date of randomization to the earliest occurrence of the following events: treatment failure per ELN, confirmed loss of MMR, progression to AP/BC, death from any cause.

For patients that have not experienced an event prior to or at the analysis cut-off date, the time will be censored at the date of last study treatment assessment or last post-treatment follow-up.

EFS is defined as the time from the date of randomization to the earliest occurrence of the following events: treatment failure as per ELN, confirmed loss of MMR ,discontinuation of study treatment due to AE, progression to AP/BC, death from any cause.

For patients that have not experienced an event prior to or at the analysis cut-off date, the time will be censored at the date of last study treatment assessment or last post-treatment follow-up.

PFS is defined as the time from the date of randomization to the earliest occurrence of progression to AP/BC or death from any cause.

For patients that have not experienced an event prior to or at the analysis cut-off date, the time will be censored at the date of last study treatment assessment or last post-treatment follow-up.

OS is defined as the time from the date of randomization to the date of death from any cause. For patients that have not experienced an event prior to or at the analysis cut-off date, the time will be censored at the date of last contact before the cut-off date.

Trough plasma concentration will measure the concentration of asciminib in the blood immediately before the next dose is administered.

Cmax is the maximum serum concentration of asciminib during a dosing interval (mass x volume-1).

Tmax is the time to reach maximum (peak) plasma drug concentration after dose administration (time)

AUCtau is the area under the plasma concentration-time curve over the dosing interval. AUClast is the area under the plasma concentration-time curve from time zero (time of dose administration) to time of last measurable concentration (mass x time x volume-1)

CL/F is the apparent total body clearance of asciminib from plasma after oral administration (volume x time-1).

The European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) assesses the quality of life of cancer patients. It consists of functioning scales, symptom scales, and the global health status quality of life (QoL) scale.

A high score for functional and QoL items/scales from the QLQ-30 represents better function and QOL. A high score in symptoms items from QLQ-30 represents worse symptoms.

The QLQ-CML24 consists of multi-scale items: symptom burden, impact on worry/mood, impact on daily life, body image problems, satisfaction with care and information and satisfaction with social life.

A higher score on most of the item scales in QLQ-CML24 reflects a larger impairment in the corresponding domain, with the exception of the satisfaction with care and information, and problems and satisfaction with social life, where a higher score reflects a higher level of satisfaction.