Chronic Myeloid Leukemia (CML) Philadelphia Chromosome Positive
Conditions
Keywords
Asciminib, Chronic Myeloid Leukemia, CML, Philadelphia Chromosome, TKIs, Bosutinib, Dasatinib, Nilotinib, Imatinib, Treatment-free remission
Brief summary
The study is designed to compare the efficacy of asciminib 80 mg QD versus Investigator selected Tyrosine Kinase Inhibitor (TKI) for the treatment of newly diagnosed, previously untreated patients with Ph+ CML-CP. The Investigator selected TKI will be one of the following treatment options for first-line treatment of CML-CP - imatinib 400 mg QD or nilotinib 300 mg BID or dasatinib 100 mg QD or bosutinib 400 mg QD. This study has three periods: 1. Treatment period for all randomized participants, 2. Optional Treatment-Free Remission (TFR) period only for participants meeting TFR eligibility criteria and 3. Treatment Re-Initiation (TRI) period only for participants who relapsed after TFR attempt.
Detailed description
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). In addition, during the TFR Period, participants who will lose major molecular response (MMR) must re-initiate treatment and will enter into a Treatment Reinitiation (TRI) Period. During the treatment period, no crossover of study treatment across arms and no change of study treatment within the Investigator selected TKI will be allowed. For specifically participants who must transition into the TRI Period, at the time of treatment re-initiation: a) participants who were previously treated with asciminib will resume asciminib at the same dose prior to entry into TFR. b) participants who were on IS-TKI may either continue with the same study treatment they were randomized to and at the same dose prior to entry into TFR or may switch to asciminib with a starting dose of 80 mg QD. Duration of Study treatment: Patients on the study will continue to receive the assigned treatment until the End of Study, premature discontinuation due to treatment failure, disease progression or intolerance, due to Investigator or participant decision. or due to patient going to TFR Period and/or TRI Period. Duration of study: The End of Study will occur 8 years from the last patient first treatment in the study. Patients who discontinue study treatment prematurely due to any reason, will be followed up for survival and progression (to AP/BC) until the End of Study.
Interventions
DRUGImatinib
Comes in 100 mg and 400 mg tablets and taken orally
DRUGNilotinib
Comes in 150 mg and 200 mg capsules and taken orally
DRUGBosutinib
Comes in 100 mg and 400 mg tablets and taken orally
DRUGDasatinib
Comes in 20 mg, 50 mg, 70 mg and 100 mg tablets and taken orally
DRUGAsciminib
Comes in 40 mg tablets and taken orally
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 100 Years
Healthy volunteers
No
Inclusion criteria
for treatment period: Participants eligible for inclusion in this study must meet all of the following criteria: * Male or female patients ≥ 18 years of age. * Participants with CML-CP within 3 months of diagnosis. * Diagnosis of CML-CP (ELN 2020 criteria) with cytogenetic confirmation of Philadelphia chromosome 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 10\^9/L (≥ 100,000/mm\^3), * No evidence of extramedullary leukemic involvement, with the exception of hepatosplenomegaly. * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. * Adequate end organ function as defined by: * Total bilirubin \< 3 x ULN; patients with Gilbert's syndrome may only be included if total bilirubin ≤ 3.0 x ULN or direct bilirubin ≤ 1.5 x ULN * Creatinine clearance (CrCl) ≥ 30 mL/min as calculated using Cockcroft-Gault formula, * Serum lipase ≤ 1.5 x ULN. For serum lipase \> ULN - ≤ 1.5 x ULN, value must be considered not clinically significant and not associated with risk factors for acute pancreatitis \- Participants must have the following laboratory values within normal limits or corrected to within normal limits with supplements prior to randomization: * Potassium (potassium increase of up to 6.0 mmol/L is acceptable if associated with CrCl\* ≥ 90 mL/min) * Total calcium (corrected for serum albumin); (calcium increase of up to 12.5 mg/dl or 3.1 mmol/L is acceptable if associated with CrCl\* ≥ 90 mL/min) * Magnesium (magnesium increase of up to 3.0 mg/dL or 1.23 mmol/L if associated with CrCl\* ≥ 90 mL/min) * For patients with mild to moderate renal impairment (CrCl\* ≥ 30 mL/min and \<90 mL/min) - potassium, total calcium (corrected for serum albumin) and magnesium should be ≥ LLN or corrected to within normal limits with supplements prior to randomization. * \*CrCl as calculated using Cockcroft-Gault formula * Ability to provide written informed consent prior to any study related screening procedures being performed. * Evidence of typical BCR-ABL1 transcript \[e14a2 and/or e13a2\] at the time of screening which is amenable to standardized Real time quantitative polymerase chain reaction (RQ-PCR) quantification.
Exclusion criteria
for Treatment period: * Previous treatment of CML with any other anticancer agents including chemotherapy and/or biologic agents or prior stem cell transplant, with the exception of hydroxyurea and/or anagrelide. Treatment with either imatinib, or nilotinib, or dasatinib or bosutinib for ≤2 weeks is allowed, but no other treatment with other tyrosine kinase inhibitors prior to randomization is permitted. * Known cytopathologically confirmed CNS infiltration (in absence of suspicion of CNS involvement, lumbar puncture not required). * Impaired cardiac function or cardiac repolarization abnormality including but not limited to any one of the following: * History within 6 months prior to starting study treatment of myocardial infarction (MI), angina pectoris, coronary artery bypass graft (CABG) * Clinically significant cardiac arrhythmias (e.g., ventricular tachycardia), complete left bundle branch block, high-grade AV block (e.g., bifascicular block, Mobitz type II and third degree AV block) * QTc ≥ 450 ms (male patients), ≥460 ms (female patients) on the average of three serial baseline ECG (using the QTcF formula) as determined by central reading. If QTcF ≥ 450 ms and electrolytes are not within normal ranges, electrolytes should be corrected and then the patient re-screened for QTc. * Long QT syndrome, family history of idiopathic sudden death or congenital long QT syndrome, or any of the following: * Risk factors for Torsades de Pointes (TdP) including uncorrected hypokalemia or hypomagnesemia, history of cardiac failure, or history of clinically significant/symptomatic bradycardia * Concomitant medication(s) with a "Known risk of Torsades de Pointes" per www.crediblemeds.org/ that cannot be discontinued or replaced 7 days prior to starting study drug by safe alternative medication.•Inability to determine the QTcF interval * Severe and/or uncontrolled concurrent medical disease that in the opinion of the investigator could cause unacceptable safety risks or compromise compliance with the protocol (e.g. uncontrolled diabetes, active or uncontrolled infection; uncontrolled arterial or pulmonary hypertension, uncontrolled clinically significant hyperlipidemia). Please refer to Section 6.3.1 * History of significant congenital or acquired bleeding disorder unrelated to cancer. * Major surgery within 4 weeks prior to study entry or who have not recovered from prior surgery. * History of other active malignancy within 3 years prior to study entry with the exception of previous or concomitant basal cell skin cancer and previous carcinoma in situ treated curatively * History of acute pancreatitis within 1 year prior to randomization or medical history of chronic pancreatitis. * History of chronic liver disease leading to severe hepatic impairment, or ongoing acute liver disease. * Known hypersensitivity to the study treatment Other protocol-defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Major Molecular Response (MMR) at Week 48 - Asciminib (Imatinib Stratum) vs Investigator Selected TKI (Imatinib Stratum) | At 48 weeks | Molecular response is assessed using BCR-ABL1 transcript levels measured by realtime quantitative polymerase chain reaction. MMR is defined as a ratio BCR-ABL1/ABL ≤0.1% on the international scale (ie, at least 3 log reduction from a standardized baseline value). |
| Percentage of Participants With Major Molecular Response (MMR) at Week 48 - Ascimimib vs. Investigator Selected TKI | At 48 weeks | Molecular response is assessed using BCR-ABL1 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Major Molecular Response at Week 96 | at 96 weeks (96 weeks after last patient first dose) | 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). |
| Time to Discontinuation of Study Treatment Due to Adverse Events (TTDAE) | 96 weeks after last patient first dose | 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. |
| Major Molecular Response at Scheduled Data Collection Time Points | Planned total follow-up duration of 5 years | 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). |
| Major Molecular Response by Scheduled Data Collection Time Points | Planned total follow-up duration of 5 years | 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). |
| MR4.0 at Scheduled Data Collection Time Points | Planned total follow-up duration of 5 years | 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). |
| MR4.5 at All Scheduled Data Collection Time Points | Planned total follow-up duration of 5 years | 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). |
| MR4.0 by Scheduled Data Collection Time Points | Planned total follow-up duration of 5 years | 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). |
| MR4.5 by All Scheduled Data Collection Time Points | Planned total follow-up duration of 5 years | 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). |
| PK of Asciminib: Tmax | Week 2 (0 hours (h) pre-dose, 1h, 2h, 3h, 4h, 6h, 8h and 12h post dose) | Tmax is the time to reach maximum (peak) plasma drug concentration after dose administration (time) |
| Complete Hematological Response (CHR) at All Scheduled Data Collection Time Points | Planned total follow-up duration of 5 years | 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 |
| Complete Hematological Response (CHR) by All Scheduled Data Collection Time Points | Planned total follow-up duration of 5 years | 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 |
| Percentage of Participants With Complete Cytogenic Response (CCyR) by Week 48 & Week 96 | By week 48 and by week 96 (48 weeks and 96 weeks after last patient first dose); data collection/analysis is ongoing for the 96 week time point, and the data will be reported later | 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 | Planned total follow-up duration of 5 years | 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 | Planned total follow-up duration of 5 years | 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 | Planned total follow-up duration of 5 years | 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 | Planned total follow-up duration of 5 years | 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 | Planned total follow-up duration of 5 years | 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 | Planned total follow-up duration of 5 years | 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. |
| BCR-ABL1≤1% at Scheduled Data Collection Time Points | Planned total follow-up duration of 5 years | Molecular response is assessed using BCR-ABL transcript levels measured by realtime quantitative polymerase chain reaction. |
| BCR-ABL1≤1% by Scheduled Data Collection Time Points | Planned total follow-up duration of 5 years | Molecular response is assessed using BCR-ABL transcript levels measured by realtime quantitative polymerase chain reaction. |
| Time to Treatment Failure (TTF) | Planned total follow-up duration of 5 years | 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) . |
| Failure Free Survival (FFS) | Planned total follow-up duration of 5 years | 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. |
| Event Free Survival (EFS) | Planned total follow-up duration of 5 years | 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. |
| Progression Free Survival (PFS) | Planned total follow-up duration of 5 years | 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. |
| Overall Survival (OS) | Planned total follow-up duration of 5 years | 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 Concentrations. | Week 48 | Trough plasma concentration will measure the concentration of asciminib in the blood immediately before the next dose is administered. |
| Pharmacokinetics (PK) of Asciminib: Cmax | Week 2 (0 hours (h) pre-dose, 1h, 2h, 3h, 4h, 6h, 8h and 12h post dose) | Cmax is the maximum serum concentration of asciminib during a dosing interval (mass x volume-1). |
| Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Baseline, week 48 and week 96 | 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. |
| PK of Asciminib: AUCtau and AUClast | Week 2 (0 hours (h) pre-dose, 1h, 2h, 3h, 4h, 6h, 8h and 12h post dose) | 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) |
| Change From Baseline in EORTC QLQ-CML24 Scales at Week 48 and Week 96 | Baseline, week 48 and week 96. | 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. |
| PK of Asciminib: CL/F | Week 2 (0 hours (h) pre-dose, 1h, 2h, 3h, 4h, 6h, 8h and 12h post dose) | CL/F is the apparent total body clearance of asciminib from plasma after oral administration (volume x time-1). |
Countries
Australia, Austria, Belgium, Bulgaria, Canada, China, Czechia, Denmark, Finland, France, Germany, Hungary, India, Israel, Italy, Japan, Malaysia, Netherlands, Norway, Portugal, Singapore, Slovakia, South Korea, Spain, Sweden, Switzerland, Taiwan, United Kingdom, United States
Contacts
STUDY_DIRECTORNovartis Pharmaceuticals
Novartis Pharmaceuticals
Participant flow
Recruitment details
All trial participants randomized in a 1:1 ratio between asciminib and investigator selected TKI (imatinib 400 mg QD, nilotinib 300 mg BD, dasatinib 100 mg QD or bosutinib 400 mg QD).
Pre-assignment details
Prior to randomization, the Investigator, in consultation with the participant, considering current treatment paradigm and participant characteristics - and comorbidities, made a selection of imatinib or 2G TKI (nilotinib, dasatinib, or bosutinib) to be used if the participant is randomized to the comparator arm. The enrolment into the strata of imatinib versus 2G TKI was managed by IRT to be approximately 50% versus 50%.
Participants by arm
| Arm | Count |
|---|---|
| Asciminib (Imatinib Stratum) Patients took asciminib 80 mg QD under fasting conditions on ongoing basis. | 101 |
| Asciminib (2nd Generation TKI Stratum) Patients took ascimimib 80 mg QD under fasting conditions on ongoing basis. | 100 |
| Investigator Selected TKI (Imatinib Stratum) Patients took on ongoing basis the Investigator selected TKI (imatinib) | 102 |
| Investigator Selected TKI (2nd Generation TKI Stratum) Patients took on ongoing basis the 2G investigator selected TKIs (nilotinib, or dasatinib, or bosutinib) | 102 |
| Total | 405 |
Baseline characteristics
| Characteristic | Asciminib (Imatinib Stratum) | Asciminib (2nd Generation TKI Stratum) | Investigator Selected TKI (Imatinib Stratum) | Investigator Selected TKI (2nd Generation TKI Stratum) | Total |
|---|---|---|---|---|---|
| Age, Customized 18 to <65 years | 69 Participants | 86 Participants | 70 Participants | 85 Participants | 310 Participants |
| Age, Customized 65 to <75 years | 24 Participants | 12 Participants | 22 Participants | 12 Participants | 70 Participants |
| Age, Customized >= 75 years | 8 Participants | 2 Participants | 10 Participants | 5 Participants | 25 Participants |
| EUTOS Long-Term Survival (ELTS) score High | 9 Participants | 14 Participants | 8 Participants | 14 Participants | 45 Participants |
| EUTOS Long-Term Survival (ELTS) score Intermediate | 30 Participants | 26 Participants | 30 Participants | 27 Participants | 113 Participants |
| EUTOS Long-Term Survival (ELTS) score Low | 62 Participants | 60 Participants | 64 Participants | 61 Participants | 247 Participants |
| Race/Ethnicity, Customized Asian | 37 Participants | 53 Participants | 34 Participants | 56 Participants | 180 Participants |
| Race/Ethnicity, Customized Black or African American | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 4 Participants |
| Race/Ethnicity, Customized Unknown | 0 Participants | 1 Participants | 1 Participants | 1 Participants | 3 Participants |
| Race/Ethnicity, Customized White | 63 Participants | 45 Participants | 66 Participants | 44 Participants | 218 Participants |
| Sex: Female, Male Female | 39 Participants | 31 Participants | 37 Participants | 42 Participants | 149 Participants |
| Sex: Female, Male Male | 62 Participants | 69 Participants | 65 Participants | 60 Participants | 256 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 200 | 0 / 99 | 0 / 102 | 0 / 201 |
| other Total, other adverse events | 177 / 200 | 89 / 99 | 100 / 102 | 189 / 201 |
| serious Total, serious adverse events | 22 / 200 | 12 / 99 | 20 / 102 | 32 / 201 |
Outcome results
Primary
Percentage of Participants With Major Molecular Response (MMR) at Week 48 - Ascimimib vs. Investigator Selected TKI
Molecular response is assessed using BCR-ABL1 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).
Time frame: At 48 weeks
Population: The Full Analysis Set (FAS) comprised of all participants to whom study treatment has been assigned by randomization.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Asciminib (All Asciminib ) | Percentage of Participants With Major Molecular Response (MMR) at Week 48 - Ascimimib vs. Investigator Selected TKI | 136 Participants |
| Investigator Selected TKI (All Comparators) | Percentage of Participants With Major Molecular Response (MMR) at Week 48 - Ascimimib vs. Investigator Selected TKI | 100 Participants |
p-value: <0.00195% CI: [9.59, 28.17]Mantel Haenszel
Primary
Percentage of Participants With Major Molecular Response (MMR) at Week 48 - Asciminib (Imatinib Stratum) vs Investigator Selected TKI (Imatinib Stratum)
Molecular response is assessed using BCR-ABL1 transcript levels measured by realtime quantitative polymerase chain reaction. MMR is defined as a ratio BCR-ABL1/ABL ≤0.1% on the international scale (ie, at least 3 log reduction from a standardized baseline value).
Time frame: At 48 weeks
Population: The IMA Full Analysis Set (FASIMA) comprised of all participants from the FAS, whose PRS TKI is imatinib. FAS comprised of all participants to whom study treatment has been assigned by randomization.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Asciminib (All Asciminib ) | Percentage of Participants With Major Molecular Response (MMR) at Week 48 - Asciminib (Imatinib Stratum) vs Investigator Selected TKI (Imatinib Stratum) | 70 Participants |
| Investigator Selected TKI (All Comparators) | Percentage of Participants With Major Molecular Response (MMR) at Week 48 - Asciminib (Imatinib Stratum) vs Investigator Selected TKI (Imatinib Stratum) | 41 Participants |
p-value: <0.00195% CI: [16.91, 42.18]Mantel Haenszel
Secondary
BCR-ABL1≤1% at Scheduled Data Collection Time Points
Molecular response is assessed using BCR-ABL transcript levels measured by realtime quantitative polymerase chain reaction.
Time frame: Planned total follow-up duration of 5 years
Secondary
BCR-ABL1≤1% by Scheduled Data Collection Time Points
Molecular response is assessed using BCR-ABL transcript levels measured by realtime quantitative polymerase chain reaction.
Time frame: Planned total follow-up duration of 5 years
Secondary
Change From Baseline in EORTC QLQ-CML24 Scales at Week 48 and Week 96
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.
Time frame: Baseline, week 48 and week 96.
Population: Full Analysis Set: All participants who had an EORTC QLQ-CML24 assessment both at baseline and at week 48.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Asciminib (All Asciminib ) | Change From Baseline in EORTC QLQ-CML24 Scales at Week 48 and Week 96 | Satisfaction with Social Life | Moderately better | 0 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in EORTC QLQ-CML24 Scales at Week 48 and Week 96 | Symptom Burden | Moderately better | 12 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in EORTC QLQ-CML24 Scales at Week 48 and Week 96 | Symptom Burden | Unchanged | 27 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in EORTC QLQ-CML24 Scales at Week 48 and Week 96 | Symptom Burden | Very much worse | 7 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in EORTC QLQ-CML24 Scales at Week 48 and Week 96 | Impact on Worry/Mood | A little better | 20 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in EORTC QLQ-CML24 Scales at Week 48 and Week 96 | Impact on Worry/Mood | Moderately worse | 2 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in EORTC QLQ-CML24 Scales at Week 48 and Week 96 | Impact on Daily Life | A little better | 0 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in EORTC QLQ-CML24 Scales at Week 48 and Week 96 | Impact on Daily Life | A little worse | 0 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in EORTC QLQ-CML24 Scales at Week 48 and Week 96 | Impact on Daily Life | Moderately worse | 6 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in EORTC QLQ-CML24 Scales at Week 48 and Week 96 | Body Image Problems | Very much better | 18 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in EORTC QLQ-CML24 Scales at Week 48 and Week 96 | Body Image Problems | Very much worse | 11 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in EORTC QLQ-CML24 Scales at Week 48 and Week 96 | Satisfaction with Care and Information | A little better | 0 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in EORTC QLQ-CML24 Scales at Week 48 and Week 96 | Satisfaction with Social Life | Unchanged | 40 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in EORTC QLQ-CML24 Scales at Week 48 and Week 96 | Satisfaction with Social Life | Moderately worse | 0 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in EORTC QLQ-CML24 Scales at Week 48 and Week 96 | Satisfaction with Social Life | Very much worse | 22 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in EORTC QLQ-CML24 Scales at Week 48 and Week 96 | Impact on Worry/Mood | Very much worse | 4 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in EORTC QLQ-CML24 Scales at Week 48 and Week 96 | Impact on Daily Life | Very much better | 21 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in EORTC QLQ-CML24 Scales at Week 48 and Week 96 | Impact on Daily Life | Moderately better | 26 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in EORTC QLQ-CML24 Scales at Week 48 and Week 96 | Impact on Daily Life | Unchanged | 19 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in EORTC QLQ-CML24 Scales at Week 48 and Week 96 | Impact on Daily Life | Very much worse | 5 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in EORTC QLQ-CML24 Scales at Week 48 and Week 96 | Body Image Problems | Moderately better | 0 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in EORTC QLQ-CML24 Scales at Week 48 and Week 96 | Body Image Problems | A little better | 0 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in EORTC QLQ-CML24 Scales at Week 48 and Week 96 | Body Image Problems | Unchanged | 48 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in EORTC QLQ-CML24 Scales at Week 48 and Week 96 | Body Image Problems | A little worse | 0 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in EORTC QLQ-CML24 Scales at Week 48 and Week 96 | Body Image Problems | Moderately worse | 0 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in EORTC QLQ-CML24 Scales at Week 48 and Week 96 | Satisfaction with Care and Information | Very much better | 8 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in EORTC QLQ-CML24 Scales at Week 48 and Week 96 | Satisfaction with Care and Information | Moderately better | 5 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in EORTC QLQ-CML24 Scales at Week 48 and Week 96 | Satisfaction with Care and Information | Unchanged | 30 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in EORTC QLQ-CML24 Scales at Week 48 and Week 96 | Satisfaction with Care and Information | A little worse | 0 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in EORTC QLQ-CML24 Scales at Week 48 and Week 96 | Satisfaction with Care and Information | Moderately worse | 18 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in EORTC QLQ-CML24 Scales at Week 48 and Week 96 | Satisfaction with Care and Information | Very much worse | 16 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in EORTC QLQ-CML24 Scales at Week 48 and Week 96 | Satisfaction with Social Life | Very much better | 15 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in EORTC QLQ-CML24 Scales at Week 48 and Week 96 | Symptom Burden | Very much better | 0 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in EORTC QLQ-CML24 Scales at Week 48 and Week 96 | Satisfaction with Social Life | A little better | 0 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in EORTC QLQ-CML24 Scales at Week 48 and Week 96 | Satisfaction with Social Life | A little worse | 0 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in EORTC QLQ-CML24 Scales at Week 48 and Week 96 | Symptom Burden | A little better | 18 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in EORTC QLQ-CML24 Scales at Week 48 and Week 96 | Symptom Burden | A little worse | 7 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in EORTC QLQ-CML24 Scales at Week 48 and Week 96 | Symptom Burden | Moderately worse | 6 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in EORTC QLQ-CML24 Scales at Week 48 and Week 96 | Impact on Worry/Mood | Very much better | 11 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in EORTC QLQ-CML24 Scales at Week 48 and Week 96 | Impact on Worry/Mood | Moderately better | 7 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in EORTC QLQ-CML24 Scales at Week 48 and Week 96 | Impact on Worry/Mood | Unchanged | 17 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in EORTC QLQ-CML24 Scales at Week 48 and Week 96 | Impact on Worry/Mood | A little worse | 16 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in EORTC QLQ-CML24 Scales at Week 48 and Week 96 | Body Image Problems | A little better | 0 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in EORTC QLQ-CML24 Scales at Week 48 and Week 96 | Symptom Burden | Very much better | 2 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in EORTC QLQ-CML24 Scales at Week 48 and Week 96 | Satisfaction with Social Life | Moderately better | 0 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in EORTC QLQ-CML24 Scales at Week 48 and Week 96 | Body Image Problems | Unchanged | 41 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in EORTC QLQ-CML24 Scales at Week 48 and Week 96 | Symptom Burden | Unchanged | 22 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in EORTC QLQ-CML24 Scales at Week 48 and Week 96 | Symptom Burden | Moderately worse | 12 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in EORTC QLQ-CML24 Scales at Week 48 and Week 96 | Impact on Worry/Mood | A little worse | 11 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in EORTC QLQ-CML24 Scales at Week 48 and Week 96 | Body Image Problems | A little worse | 0 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in EORTC QLQ-CML24 Scales at Week 48 and Week 96 | Impact on Worry/Mood | A little better | 6 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in EORTC QLQ-CML24 Scales at Week 48 and Week 96 | Impact on Worry/Mood | Unchanged | 18 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in EORTC QLQ-CML24 Scales at Week 48 and Week 96 | Satisfaction with Social Life | A little better | 0 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in EORTC QLQ-CML24 Scales at Week 48 and Week 96 | Body Image Problems | Moderately worse | 0 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in EORTC QLQ-CML24 Scales at Week 48 and Week 96 | Body Image Problems | Very much worse | 15 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in EORTC QLQ-CML24 Scales at Week 48 and Week 96 | Satisfaction with Social Life | Unchanged | 37 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in EORTC QLQ-CML24 Scales at Week 48 and Week 96 | Satisfaction with Care and Information | Very much better | 13 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in EORTC QLQ-CML24 Scales at Week 48 and Week 96 | Symptom Burden | Very much worse | 5 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in EORTC QLQ-CML24 Scales at Week 48 and Week 96 | Satisfaction with Care and Information | Moderately better | 4 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in EORTC QLQ-CML24 Scales at Week 48 and Week 96 | Satisfaction with Social Life | A little worse | 0 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in EORTC QLQ-CML24 Scales at Week 48 and Week 96 | Satisfaction with Care and Information | A little better | 0 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in EORTC QLQ-CML24 Scales at Week 48 and Week 96 | Satisfaction with Care and Information | Unchanged | 31 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in EORTC QLQ-CML24 Scales at Week 48 and Week 96 | Symptom Burden | Moderately better | 4 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in EORTC QLQ-CML24 Scales at Week 48 and Week 96 | Satisfaction with Social Life | Moderately worse | 0 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in EORTC QLQ-CML24 Scales at Week 48 and Week 96 | Satisfaction with Care and Information | A little worse | 0 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in EORTC QLQ-CML24 Scales at Week 48 and Week 96 | Satisfaction with Social Life | Very much worse | 15 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in EORTC QLQ-CML24 Scales at Week 48 and Week 96 | Impact on Worry/Mood | Moderately worse | 4 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in EORTC QLQ-CML24 Scales at Week 48 and Week 96 | Impact on Worry/Mood | Moderately better | 9 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in EORTC QLQ-CML24 Scales at Week 48 and Week 96 | Impact on Worry/Mood | Very much worse | 11 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in EORTC QLQ-CML24 Scales at Week 48 and Week 96 | Satisfaction with Care and Information | Moderately worse | 7 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in EORTC QLQ-CML24 Scales at Week 48 and Week 96 | Impact on Daily Life | Very much better | 17 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in EORTC QLQ-CML24 Scales at Week 48 and Week 96 | Symptom Burden | A little better | 5 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in EORTC QLQ-CML24 Scales at Week 48 and Week 96 | Impact on Daily Life | Moderately better | 10 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in EORTC QLQ-CML24 Scales at Week 48 and Week 96 | Impact on Daily Life | A little better | 0 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in EORTC QLQ-CML24 Scales at Week 48 and Week 96 | Satisfaction with Care and Information | Very much worse | 11 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in EORTC QLQ-CML24 Scales at Week 48 and Week 96 | Impact on Daily Life | Unchanged | 23 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in EORTC QLQ-CML24 Scales at Week 48 and Week 96 | Impact on Daily Life | A little worse | 0 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in EORTC QLQ-CML24 Scales at Week 48 and Week 96 | Impact on Daily Life | Moderately worse | 5 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in EORTC QLQ-CML24 Scales at Week 48 and Week 96 | Impact on Worry/Mood | Very much better | 7 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in EORTC QLQ-CML24 Scales at Week 48 and Week 96 | Impact on Daily Life | Very much worse | 11 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in EORTC QLQ-CML24 Scales at Week 48 and Week 96 | Body Image Problems | Very much better | 10 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in EORTC QLQ-CML24 Scales at Week 48 and Week 96 | Satisfaction with Social Life | Very much better | 14 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in EORTC QLQ-CML24 Scales at Week 48 and Week 96 | Body Image Problems | Moderately better | 0 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in EORTC QLQ-CML24 Scales at Week 48 and Week 96 | Symptom Burden | A little worse | 16 Participants |
Secondary
Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96
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.
Time frame: Baseline, week 48 and week 96
Population: Full Analysis Set: All participants who had an EORTC QLQ-C30 assessment both at baseline and at week 48.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Asciminib (All Asciminib ) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Cognitive functioning | A little worse | 0 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Dyspnoea | A little better | 0 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Dyspnoea | Very much better | 11 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Dyspnoea | Unchanged | 59 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Dyspnoea | A little worse | 0 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Global health status/QoL | Very much worse | 2 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Dyspnoea | Moderately worse | 0 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Dyspnoea | Very much worse | 9 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Insomnia | Moderately better | 0 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Insomnia | Very much better | 14 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Insomnia | A little better | 0 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Social functioning | Very much better | 7 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Insomnia | Unchanged | 50 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Insomnia | Moderately worse | 0 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Insomnia | A little worse | 0 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Insomnia | Very much worse | 15 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Role functioning | A little better | 0 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Appetite loss | Very much better | 16 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Appetite loss | Moderately better | 0 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Social functioning | A little better | 0 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Appetite loss | A little better | 0 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Emotional functioning | A little better | 14 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Appetite loss | Unchanged | 59 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Appetite loss | A little worse | 0 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Appetite loss | Moderately worse | 0 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Appetite loss | Very much worse | 4 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Constipation | Moderately worse | 0 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Constipation | Very much better | 8 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Constipation | Very much worse | 13 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Constipation | Moderately better | 0 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Diarrhoea | Moderately better | 0 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Constipation | A little better | 0 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Diarrhoea | Unchanged | 61 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Constipation | Unchanged | 58 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Social functioning | Unchanged | 51 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Constipation | A little worse | 0 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Global health status/QoL | A little better | 6 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Diarrhoea | Very much worse | 7 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Emotional functioning | A little worse | 7 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Diarrhoea | Very much better | 11 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Financial difficulties | Unchanged | 63 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Social functioning | A little worse | 0 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Diarrhoea | A little better | 0 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Social functioning | Moderately worse | 4 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Diarrhoea | A little worse | 0 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Global health status/QoL | Very much better | 10 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Social functioning | Very much worse | 3 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Global health status/QoL | Moderately better | 18 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Global health status/QoL | Unchanged | 28 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Fatigue | Very much better | 19 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Physical functioning | Very much better | 3 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Physical functioning | A little better | 16 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Fatigue | Moderately better | 16 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Physical functioning | Unchanged | 32 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Fatigue | A little better | 0 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Physical functioning | A little worse | 7 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Emotional functioning | Moderately worse | 5 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Fatigue | Unchanged | 26 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Physical functioning | Moderately worse | 10 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Physical functioning | Very much worse | 1 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Nausea and vomiting | Moderately better | 7 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Role functioning | Very much better | 5 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Fatigue | A little worse | 0 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Role functioning | Moderately better | 10 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Role functioning | Unchanged | 54 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Physical functioning | Moderately better | 10 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Role functioning | A little worse | 0 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Diarrhoea | Moderately worse | 0 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Fatigue | Moderately worse | 11 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Nausea and vomiting | A little better | 0 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Role functioning | Moderately worse | 4 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Fatigue | Very much worse | 7 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Role functioning | Very much worse | 6 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Cognitive functioning | Moderately better | 13 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Emotional functioning | Very much better | 9 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Nausea and vomiting | Very much better | 1 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Emotional functioning | Moderately better | 7 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Cognitive functioning | A little better | 0 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Emotional functioning | Unchanged | 31 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Nausea and vomiting | Unchanged | 67 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Nausea and vomiting | Very much worse | 1 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Nausea and vomiting | A little worse | 0 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Global health status/QoL | Moderately worse | 10 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Financial difficulties | Very much better | 12 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Emotional functioning | Very much worse | 6 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Financial difficulties | Moderately better | 0 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Nausea and vomiting | Moderately worse | 3 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Cognitive functioning | Very much better | 3 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Pain | Moderately better | 17 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Financial difficulties | A little better | 0 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Pain | Very much better | 9 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Cognitive functioning | Unchanged | 44 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Pain | A little better | 0 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Financial difficulties | A little worse | 0 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Pain | Moderately worse | 5 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Cognitive functioning | Moderately worse | 16 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Pain | Unchanged | 45 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Cognitive functioning | Very much worse | 3 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Pain | Very much worse | 3 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Global health status/QoL | A little worse | 5 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Social functioning | Moderately better | 14 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Financial difficulties | Moderately worse | 0 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Pain | A little worse | 0 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Financial difficulties | Very much worse | 4 Participants |
| Asciminib (All Asciminib ) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Dyspnoea | Moderately better | 0 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Financial difficulties | Very much worse | 7 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Global health status/QoL | A little better | 6 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Global health status/QoL | Unchanged | 26 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Global health status/QoL | A little worse | 6 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Global health status/QoL | Moderately worse | 12 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Physical functioning | Very much better | 3 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Physical functioning | Moderately better | 12 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Physical functioning | Moderately worse | 6 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Role functioning | Moderately better | 7 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Emotional functioning | A little better | 9 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Emotional functioning | Very much worse | 6 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Cognitive functioning | A little better | 0 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Cognitive functioning | Unchanged | 36 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Cognitive functioning | A little worse | 0 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Social functioning | Moderately better | 6 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Social functioning | A little better | 0 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Social functioning | Unchanged | 40 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Social functioning | A little worse | 0 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Fatigue | Moderately better | 16 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Nausea and vomiting | Moderately better | 5 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Nausea and vomiting | A little better | 0 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Nausea and vomiting | Moderately worse | 11 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Pain | Very much better | 3 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Pain | A little better | 0 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Pain | Unchanged | 37 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Pain | A little worse | 0 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Dyspnoea | Unchanged | 49 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Insomnia | A little better | 0 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Insomnia | A little worse | 0 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Appetite loss | Unchanged | 51 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Appetite loss | A little worse | 0 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Diarrhoea | Unchanged | 43 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Diarrhoea | A little worse | 0 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Financial difficulties | Very much better | 14 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Social functioning | Moderately worse | 7 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Social functioning | Very much worse | 11 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Fatigue | Very much better | 11 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Fatigue | A little better | 0 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Fatigue | Unchanged | 16 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Fatigue | A little worse | 0 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Fatigue | Moderately worse | 11 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Fatigue | Very much worse | 16 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Nausea and vomiting | Very much better | 1 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Nausea and vomiting | Unchanged | 48 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Nausea and vomiting | A little worse | 0 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Nausea and vomiting | Very much worse | 5 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Pain | Moderately better | 11 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Pain | Moderately worse | 10 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Pain | Very much worse | 9 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Dyspnoea | Very much better | 9 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Dyspnoea | Moderately better | 0 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Dyspnoea | A little better | 0 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Dyspnoea | A little worse | 0 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Dyspnoea | Moderately worse | 0 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Dyspnoea | Very much worse | 12 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Insomnia | Very much better | 10 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Insomnia | Moderately better | 0 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Insomnia | Unchanged | 43 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Insomnia | Moderately worse | 0 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Insomnia | Very much worse | 17 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Appetite loss | Very much better | 11 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Appetite loss | Moderately better | 0 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Appetite loss | A little better | 0 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Appetite loss | Moderately worse | 0 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Appetite loss | Very much worse | 8 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Constipation | Very much better | 14 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Constipation | Moderately better | 0 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Constipation | A little better | 0 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Constipation | Unchanged | 40 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Constipation | A little worse | 0 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Constipation | Moderately worse | 0 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Constipation | Very much worse | 16 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Diarrhoea | Very much better | 8 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Diarrhoea | Moderately better | 0 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Diarrhoea | A little better | 0 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Global health status/QoL | Very much better | 6 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Global health status/QoL | Very much worse | 7 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Physical functioning | A little better | 12 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Physical functioning | Unchanged | 26 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Role functioning | A little better | 0 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Physical functioning | A little worse | 8 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Physical functioning | Very much worse | 3 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Role functioning | Very much better | 7 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Role functioning | Unchanged | 41 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Diarrhoea | Moderately worse | 0 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Role functioning | A little worse | 0 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Role functioning | Moderately worse | 7 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Role functioning | Very much worse | 8 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Emotional functioning | Very much better | 10 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Emotional functioning | Moderately better | 6 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Emotional functioning | Unchanged | 24 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Emotional functioning | A little worse | 10 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Diarrhoea | Very much worse | 19 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Emotional functioning | Moderately worse | 5 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Financial difficulties | Moderately better | 0 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Cognitive functioning | Very much better | 1 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Financial difficulties | A little better | 0 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Cognitive functioning | Moderately better | 8 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Financial difficulties | Unchanged | 49 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Financial difficulties | A little worse | 0 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Cognitive functioning | Moderately worse | 19 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Cognitive functioning | Very much worse | 6 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Social functioning | Very much better | 6 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Financial difficulties | Moderately worse | 0 Participants |
| Investigator Selected TKI (All Comparators) | Change From Baseline in Overall Scores (Global Health Status) and Individual Scales of the EORTC QLQ-C30 at Week 48 and Week 96 | Global health status/QoL | Moderately better | 7 Participants |
Secondary
Complete Hematological Response (CHR) at All Scheduled Data Collection Time Points
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
Time frame: Planned total follow-up duration of 5 years
Secondary
Complete Hematological Response (CHR) by All Scheduled Data Collection Time Points
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
Time frame: Planned total follow-up duration of 5 years
Secondary
Duration of MMR
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
Time frame: Planned total follow-up duration of 5 years
Secondary
Duration of MR4.0
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
Time frame: Planned total follow-up duration of 5 years
Secondary
Duration of MR4.5
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 frame: Planned total follow-up duration of 5 years
Secondary
Event Free Survival (EFS)
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.
Time frame: Planned total follow-up duration of 5 years
Secondary
Failure Free Survival (FFS)
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.
Time frame: Planned total follow-up duration of 5 years
Secondary
Major Molecular Response at Scheduled Data Collection Time Points
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).
Time frame: Planned total follow-up duration of 5 years
Secondary
Major Molecular Response at Week 96
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).
Time frame: at 96 weeks (96 weeks after last patient first dose)
Secondary
Major Molecular Response by Scheduled Data Collection Time Points
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).
Time frame: Planned total follow-up duration of 5 years
Secondary
MR4.0 at Scheduled Data Collection Time Points
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).
Time frame: Planned total follow-up duration of 5 years
Secondary
MR4.0 by Scheduled Data Collection Time Points
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).
Time frame: Planned total follow-up duration of 5 years
Secondary
MR4.5 at All Scheduled Data Collection Time Points
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).
Time frame: Planned total follow-up duration of 5 years
Secondary
MR4.5 by All Scheduled Data Collection Time Points
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).
Time frame: Planned total follow-up duration of 5 years
Secondary
Overall Survival (OS)
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.
Time frame: Planned total follow-up duration of 5 years
Secondary
Percentage of Participants With Complete Cytogenic Response (CCyR) by Week 48 & Week 96
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.
Time frame: By week 48 and by week 96 (48 weeks and 96 weeks after last patient first dose); data collection/analysis is ongoing for the 96 week time point, and the data will be reported later
Population: The Full Analysis Set (FAS) comprised of all participants to whom study treatment has been assigned by randomization and who had a valid bone marrow examination at week 48.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Asciminib (All Asciminib ) | Percentage of Participants With Complete Cytogenic Response (CCyR) by Week 48 & Week 96 | Partial cytogenetic response (PCyR) | 1 Participants |
| Asciminib (All Asciminib ) | Percentage of Participants With Complete Cytogenic Response (CCyR) by Week 48 & Week 96 | Minimal cytogenetic response | 0 Participants |
| Asciminib (All Asciminib ) | Percentage of Participants With Complete Cytogenic Response (CCyR) by Week 48 & Week 96 | Minor cytogenetic response (mCyR) | 0 Participants |
| Asciminib (All Asciminib ) | Percentage of Participants With Complete Cytogenic Response (CCyR) by Week 48 & Week 96 | No cytogenetic response | 0 Participants |
| Asciminib (All Asciminib ) | Percentage of Participants With Complete Cytogenic Response (CCyR) by Week 48 & Week 96 | Complete cytogenetic response (CCyR) | 1 Participants |
| Investigator Selected TKI (All Comparators) | Percentage of Participants With Complete Cytogenic Response (CCyR) by Week 48 & Week 96 | No cytogenetic response | 0 Participants |
| Investigator Selected TKI (All Comparators) | Percentage of Participants With Complete Cytogenic Response (CCyR) by Week 48 & Week 96 | Complete cytogenetic response (CCyR) | 0 Participants |
| Investigator Selected TKI (All Comparators) | Percentage of Participants With Complete Cytogenic Response (CCyR) by Week 48 & Week 96 | Partial cytogenetic response (PCyR) | 0 Participants |
| Investigator Selected TKI (All Comparators) | Percentage of Participants With Complete Cytogenic Response (CCyR) by Week 48 & Week 96 | Minor cytogenetic response (mCyR) | 0 Participants |
| Investigator Selected TKI (All Comparators) | Percentage of Participants With Complete Cytogenic Response (CCyR) by Week 48 & Week 96 | Minimal cytogenetic response | 0 Participants |
Secondary
Pharmacokinetics (PK) of Asciminib: Cmax
Cmax is the maximum serum concentration of asciminib during a dosing interval (mass x volume-1).
Time frame: Week 2 (0 hours (h) pre-dose, 1h, 2h, 3h, 4h, 6h, 8h and 12h post dose)
Population: Full PK samples were collected at Week 2
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Asciminib (All Asciminib ) | Pharmacokinetics (PK) of Asciminib: Cmax | 1470 ng/mL | Geometric Coefficient of Variation 38.2 |
Secondary
PK of Asciminib: AUCtau and AUClast
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)
Time frame: Week 2 (0 hours (h) pre-dose, 1h, 2h, 3h, 4h, 6h, 8h and 12h post dose)
Population: Full PK samples were collected at Week 2. Although samples were collected for 26 participants, AUCtau could not be evaluated because extrapolated AUC was over 20% for all participants.~AUCtau is derived from extrapolated AUC. However, when it is over 20% for all participants, AUCtau cannot be determined.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Asciminib (All Asciminib ) | PK of Asciminib: AUCtau and AUClast | AUClast | 8590 ng*hr/mL | Geometric Coefficient of Variation 42.2 |
| Asciminib (All Asciminib ) | PK of Asciminib: AUCtau and AUClast | AUCtau | NA ng*hr/mL | — |
Secondary
PK of Asciminib: CL/F
CL/F is the apparent total body clearance of asciminib from plasma after oral administration (volume x time-1).
Time frame: Week 2 (0 hours (h) pre-dose, 1h, 2h, 3h, 4h, 6h, 8h and 12h post dose)
Population: Although samples were collected for 26 participants, CL/F could not be evaluated because extrapolated AUC was over 20% for all participants. CL/F is derived from extrapolated AUC. However, when it is over 20% for all participants, CL/F cannot be determined.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Asciminib (All Asciminib ) | PK of Asciminib: CL/F | NA ng*hr/mL |
Secondary
PK of Asciminib: Tmax
Tmax is the time to reach maximum (peak) plasma drug concentration after dose administration (time)
Time frame: Week 2 (0 hours (h) pre-dose, 1h, 2h, 3h, 4h, 6h, 8h and 12h post dose)
Population: Full PK samples were collected at Week 2
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Asciminib (All Asciminib ) | PK of Asciminib: Tmax | 2.00 Hour (hr) |
Secondary
Progression Free Survival (PFS)
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.
Time frame: Planned total follow-up duration of 5 years
Secondary
Time to Discontinuation of Study Treatment Due to Adverse Events (TTDAE)
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.
Time frame: 96 weeks after last patient first dose
Secondary
Time to First MMR
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 frame: Planned total follow-up duration of 5 years
Secondary
Time to First MR4.0
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 frame: Planned total follow-up duration of 5 years
Secondary
Time to First MR4.5
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.
Time frame: Planned total follow-up duration of 5 years
Secondary
Time to Treatment Failure (TTF)
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) .
Time frame: Planned total follow-up duration of 5 years
Secondary
Trough Plasma Concentrations.
Trough plasma concentration will measure the concentration of asciminib in the blood immediately before the next dose is administered.
Time frame: Week 48
Population: Pharmacokinetic analysis set (PAS): All participants to whom study treatment has been assigned by randomization to asciminib and that had a valid trough plasma concentration taken at week 48.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Asciminib (All Asciminib ) | Trough Plasma Concentrations. | 161 ng/mL |