Asciminib Treatment Optimization in ≥ 3rd Line CML-CP

Major Molecular Response (MMR) is defined as a significant reduction in the level of BCR::ABL1 transcripts, which are the genetic markers of chronic myeloid leukemia (CML). Specifically, MMR is achieved when there is a ≥ 3.0 log reduction in BCR::ABL1 transcripts compared to a standardized baseline, which corresponds to a BCR::ABL1/ABL1 ratio of ≤ 0.1% on the international scale (IS). The Major Molecular Response (MMR) rate at Week 48 for all patients with no evidence of MMR at baseline refers to the percentage of patients who achieve MMR after 48 weeks of treatment, despite not having MMR at the start.

Time frame: Week 48

Population: Full Analysis Set (FAS)

The MD Anderson Symptom Inventory - Chronic Myeloid Leukemia (MDASI-CML) is a 26 item self-administered questionnaire for adult CML patients. Twenty of the items measure the severity of disease-related symptoms (symptom burden) and are scored from 0 (not present) to 10 (as bad as you can imagine) and 6 items that measure symptom interference with daily life (interference) scored from 0 (did not interfere) to 10 (interfered completely). For symptom burden, total scores range from 0 to 200 and for interference range from 0 to 60, with higher scores indicates high impact on severity of chronic myeloid leukemia-related symptoms and on impact of these symptoms on daily functioning for the patient.

Time frame: Week 4, 12, 24, 48, 72, 96, 120 and at end of treatment (up to 144 weeks).

The cumulative molecular response rate refers to the proportion of subjects achieving a BCR::ABL1 level of ≤ 10% on the international scale (IS) over a specified period.

Time frame: From enrollment to end of treatment up to 144 weeks.

The cumulative molecular response rate refers to the proportion of subjects achieving a BCR::ABL1 level of ≤ 1% on the international scale (IS) over a specified period.

Time frame: From enrollment to end of treatment up to 144 weeks.

The cumulative molecular response rate refers to the proportion of subjects achieving MMR, defined as a BCR::ABL1 ratio of ≤ 0.1% on the international scale (IS), over a specified period.

Time frame: From enrollment to end of treatment up to 144 weeks.

The cumulative molecular response rate refers to the proportion of subjects achieving MR4.5, defined as a ≥ 4.5 log reduction in BCR::ABL1 transcripts compared to the standardized baseline, equivalent to 0.0032% BCR::ABL1/ABL1 by the international scale (IS), over a specified period.

Time frame: From enrollment to end of treatment up to 144 weeks.

The cumulative molecular response rate refers to the proportion of subjects achieving MR4, defined as a ≥ 4 log reduction in BCR::ABL1 transcripts compared to the standardized baseline, equivalent to 0.01% BCR::ABL1/ABL1 by the international scale (IS), over a specified period.

Time frame: From enrollment to end of treatment up to 144 weeks.

Deep molecular responses (MR4.5) is defined as a ≥ 4.5 log reduction in BCR::ABL1 transcripts compared to the standardized baseline, equivalent to 0.0032% BCR::ABL1/ABL1 by the international scale (IS).

Time frame: Week 12, 24, 36, 48, 72, 96 and 144.

Deep molecular responses (MR4) is defined as a ≥ 4 log reduction in BCR::ABL1 transcripts compared to the standardized baseline, equivalent to 0.01% BCR::ABL1/ABL1 by the international scale (IS).

Time frame: Week 12, 24, 36, 48, 72, 96 and 144.

Duration of MMR is defined as the time from the date of first documented MMR to the earliest date of loss of MMR, progression to accelerated phase (AP) or blast crisis (BC), or CML-related death. The duration of MMR is analyzed for the subjects in FAS who achieved MMR at any time.

Time frame: From the date of the first documented molecular response at MMR level to the date of first documented loss of the response level or death due to any cause, whichever occurs first, assessed up to 144 weeks.

Duration of MR4 without loss of MMR refers to the period during which a patient maintains a deep molecular response (MR4) without experiencing a loss of Major Molecular Response (MMR).

Time frame: From the date of first documented MR4 without loss of MMR to the date of first documented loss of the response level or death due to any cause, whichever occurs first, assessed up to 144 weeks.

The Major Molecular Response (MMR) rate at Week 48 for patients with MMR at baseline refers to the percentage of patients who maintain or achieve MMR after 48 weeks of treatment. MMR itself is defined as achieving a BCR::ABL1 ratio of ≤ 0.1%.

Time frame: Week 48.

Population: Full Analysis Set 2 (FAS 2) and with evaluable data at the pre-specified time points

The Major Molecular Response (MMR) rate at alternative time points (weeks 12, 24, 36, 72, 96 and 144) for all patients with no evidence of MMR at baseline refers to the percentage of patients who achieve MMR after those respective weeks of treatment, despite not having MMR at the start. MMR itself is defined as achieving a BCR::ABL1 ratio of ≤ 0.1%.

Time frame: Week 12, 24, 36, 72, 96 and 144

High-risk additional chromosomal abnormalities (ACAs) are specific chromosomal abnormalities that are considered to increase the risk in Philadelphia chromosome-positive (Ph+) cells.

Time frame: Up to 144 weeks

Overall Survival (OS) is defined as the time from treatment assignment to death due to any cause during study, assessed up to 144 weeks. Subjects who are alive at the time of the analysis data cutoff date will be censored at the date of last contact before the cut-off date. OS (in months) is calculated as: (date of death or censoring date - date of randomization + 1)/30.4375.

Time frame: Up to 144 weeks.

Progression-Free Survival (PFS) is defined as the time from the date of randomization to the earliest occurrence of documented disease progression to AP/BC or the date of death from any cause, assessed up to approximately 144 weeks. The time will be censored at the date of last study assessment (PCR, cytogenetic, hematologic or extramedullary) or last post-treatment follow-up for subjects without event. PFS (in months) is calculated as: (date of disease progression/death or censoring date - date of randomization +1)/30.4375.

Time frame: Up to 144 weeks.

The rate of BCR::ABL1 ≤ 10% refers to the percentage of patients who achieve a BCR::ABL1 level of 10% or lower within the first 48 weeks of treatment.

Time frame: Week 12, 24, 36 and 48

Population: Full Analysis Set (FAS)

The rate of BCR::ABL1 ≤ 1% refers to the percentage of patients who achieve a BCR::ABL1 level of 1% or lower within the first 48 weeks of treatment.

Time frame: Week 12, 24, 36 and 48.

Population: Full Analysis Set (FAS)

Cytogenetic Response is assessed based on the percentage of Philadelphia chromosome-positive (Ph+) metaphases in the bone marrow, with a review of at least 20 metaphases required. Complete Cytogenetic Response (CCyR) is defined as 0% Ph+ metaphases in the bone marrow.

Time frame: Week 48 and end of treatment (up to 144 weeks)

Time to MMR defined as the time from the date of randomization to the date of the first documented MMR. MMR itself is defined as achieving a BCR::ABL1 ratio of ≤ 0.1%.

Time frame: From the date of enrollment to the date of first documented MMR, assessed up to 144 weeks

Time from treatment assignment to treatment failure is defined as BCR-ABL1\>10%, assessed up to 144 weeks. For subjects who have not reached treatment failure, their TTFs will be censored at the time of last study assessment (PCR, cytogenetic, hematologic or extramedullary) before the cut-off date. TTF (in months) is calculated as: (date of treatment failure or censoring date - date of randomization + 1)/30.4375.

Time frame: Up to 144 weeks.