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

A Phase III, Multi-center, Open-label, Randomized Study of Oral Asciminib Versus Investigator Selected TKI in Patients With Newly Diagnosed Philadelphia Chromosome Positive Chronic Myelogenous Leukemia in Chronic Phase

The study is designed to compare the efficacy of asciminib 80 mg QD versus Investigator selected 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.

Study Overview

• Status: Active, not recruiting
• Conditions: Chronic Myeloid Leukemia (CML) Philadelphia Chromosome Positive
• Intervention / Treatment: Drug: Asciminib; Drug: Imatinib; Drug: Nilotinib; Drug: Bosutinib; Drug: Dasatinib

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.

The study is designed to compare the efficacy of asciminib 80 mg QD with Investigator selected TKI for the treatment of newly diagnosed, previously untreated patients with Ph+ CML-CP. The Investigator selected TKI will be one of the treatment options approved by major Health Authorities 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.

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

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.

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.

No crossover of study treatment across arms and no change of study treatment within the Investigator selected TKI will be allowed.

Duration of Study treatment: Patients on the study will continue to receive the assigned treatment until the End of Study, or until premature discontinuation due to treatment failure, disease progression or intolerance or due to Investigator or participant decision.

Duration of study: The End of Study will occur 5 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.

• Study Type: Interventional
• Enrollment (Actual): 404
• Phase: Phase 3

Expanded Access

Available outside the clinical trial. See expanded access record.

Contacts and Locations

Study Locations

• Australia
  • SouthPort, Australia, 4215
    • Novartis Investigative Site
  • New South Wales
    • Kingswood, New South Wales, Australia, 2747
      • Novartis Investigative Site
    • Port Macquarie, New South Wales, Australia, 2444
      • Novartis Investigative Site
  • Queensland
    • Woolloongabba, Queensland, Australia, 4102
      • Novartis Investigative Site
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Novartis Investigative Site
• Austria
  • Upper Austria
    • Linz, Upper Austria, Austria, 4010
      • Novartis Investigative Site
• Belgium
  • Bruxelles, Belgium, 1000
    • Novartis Investigative Site
  • Leuven, Belgium, 3000
    • Novartis Investigative Site
• Bulgaria
  • Varna, Bulgaria, 9010
    • Novartis Investigative Site
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4N2
      • Novartis Investigative Site
  • Ontario
    • Hamilton, Ontario, Canada, L8V 1C3
      • Novartis Investigative Site
    • Ottawa, Ontario, Canada, K1H 8L6
      • Novartis Investigative Site
    • Toronto, Ontario, Canada, M5G 2M9
      • Novartis Investigative Site
• China
  • Beijing, China, 100044
    • Novartis Investigative Site
  • Beijing, China, 100730
    • Novartis Investigative Site
  • Lanzhou, China, 730000
    • Novartis Investigative Site
  • Tianjin, China, 300020
    • Novartis Investigative Site
  • Guangdong
    • Guangzhou, Guangdong, China, 510515
      • Novartis Investigative Site
    • Shenzhen, Guangdong, China, 518037
      • Novartis Investigative Site
  • Henan
    • Zhengzhou, Henan, China, 450008
      • Novartis Investigative Site
  • Hubei
    • Wuhan, Hubei, China, 430022
      • Novartis Investigative Site
  • Jiangsu
    • Nanjing, Jiangsu, China, 210000
      • Novartis Investigative Site
    • Suzhou, Jiangsu, China, 215006
      • Novartis Investigative Site
  • Shanxi
    • Xian, Shanxi, China, 710068
      • Novartis Investigative Site
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • Novartis Investigative Site
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310003
      • Novartis Investigative Site
    • Wenzhou, Zhejiang, China, 325000
      • Novartis Investigative Site
• Czechia
  • CZE
    • Hradec Kralove, CZE, Czechia, 500 05
      • Novartis Investigative Site
  • Czech Republic
    • Brno Bohunice, Czech Republic, Czechia, 625 00
      • Novartis Investigative Site
  • Poruba
    • Ostrava, Poruba, Czechia, 708 52
      • Novartis Investigative Site
• Denmark
  • Aarhus, Denmark, 8000
    • Novartis Investigative Site
  • Copenhagen, Denmark, DK-2100
    • Novartis Investigative Site
• Finland
  • Helsinki, Finland, FIN 00290
    • Novartis Investigative Site
• France
  • Bordeaux, France, 33076
    • Novartis Investigative Site
  • Lyon, France, 69373
    • Novartis Investigative Site
  • Nantes Cedex 1, France, 44093
    • Novartis Investigative Site
  • Paris 10, France, 75475
    • Novartis Investigative Site
• Germany
  • Aachen, Germany, 52074
    • Novartis Investigative Site
  • Berlin, Germany, 13353
    • Novartis Investigative Site
  • Frankfurt, Germany, 60590
    • Novartis Investigative Site
  • Jena, Germany, 07740
    • Novartis Investigative Site
  • Luebeck, Germany, 23538
    • Novartis Investigative Site
  • Baden Wuerttemberg
    • Mannheim, Baden Wuerttemberg, Germany, 68305
      • Novartis Investigative Site
• Hungary
  • Debrecen, Hungary, 4032
    • Novartis Investigative Site
  • Kaposvar, Hungary, 7400
    • Novartis Investigative Site
  • Kecskemet, Hungary, 6001
    • Novartis Investigative Site
• India
  • Delhi, India, 110 085
    • Novartis Investigative Site
• Israel
  • Petah Tikva, Israel, 4941492
    • Novartis Investigative Site
  • Ramat Gan, Israel, 52621
    • Novartis Investigative Site
  • Tel Aviv, Israel, 6423906
    • Novartis Investigative Site
• Italy
  • BO
    • Bologna, BO, Italy, 40138
      • Novartis Investigative Site
  • MI
    • Milano, MI, Italy, 20122
      • Novartis Investigative Site
  • RE
    • Reggio Emilia, RE, Italy, 42123
      • Novartis Investigative Site
  • RM
    • Roma, RM, Italy, 00161
      • Novartis Investigative Site
  • VR
    • Verona, VR, Italy, 37126
      • Novartis Investigative Site
• Japan
  • Akita, Japan, 010-8543
    • Novartis Investigative Site
  • Osaka, Japan, 545-8586
    • Novartis Investigative Site
  • Yamagata, Japan, 990 9585
    • Novartis Investigative Site
  • Aichi
    • Nagoya, Aichi, Japan, 453-8511
      • Novartis Investigative Site
    • Toyoake city, Aichi, Japan, 470 1192
      • Novartis Investigative Site
  • Fukuoka
    • Fukuoka city, Fukuoka, Japan, 812-8582
      • Novartis Investigative Site
  • Fukushima
    • Fukushima city, Fukushima, Japan, 960 1295
      • Novartis Investigative Site
  • Hokkaido
    • Sapporo city, Hokkaido, Japan, 060 8648
      • Novartis Investigative Site
  • Hyogo
    • Kobe-city, Hyogo, Japan, 650-0047
      • Novartis Investigative Site
  • Okayama
    • Kurashiki-city, Okayama, Japan, 710-8602
      • Novartis Investigative Site
  • Osaka
    • Osaka Sayama, Osaka, Japan, 589 8511
      • Novartis Investigative Site
    • Suita, Osaka, Japan, 565 0871
      • Novartis Investigative Site
  • Tochigi
    • Shimotsuke, Tochigi, Japan, 329-0498
      • Novartis Investigative Site
  • Yamanashi
    • Chuo-city, Yamanashi, Japan, 409-3898
      • Novartis Investigative Site
• Korea, Republic of
  • Seoul, Korea, Republic of, 03080
    • Novartis Investigative Site
  • Seoul, Korea, Republic of, 06351
    • Novartis Investigative Site
  • Gyeonggi Do
    • Uijeongbu si, Gyeonggi Do, Korea, Republic of, 11759
      • Novartis Investigative Site
  • Seocho Gu
    • Seoul, Seocho Gu, Korea, Republic of, 06591
      • Novartis Investigative Site
• Malaysia
  • Pulau Pinang, Malaysia, 10990
    • Novartis Investigative Site
  • Selangor, Malaysia, 68000
    • Novartis Investigative Site
  • Pahang
    • Kuantan, Pahang, Malaysia, 25100
      • Novartis Investigative Site
  • Selangor
    • Subang Jaya, Selangor, Malaysia, 47500
      • Novartis Investigative Site
• Netherlands
  • Amsterdam, Netherlands, 1081 HV
    • Novartis Investigative Site
• Norway
  • Bergen, Norway, 5021
    • Novartis Investigative Site
  • Oslo, Norway, 0372
    • Novartis Investigative Site
• Portugal
  • Porto, Portugal, 4200-072
    • Novartis Investigative Site
  • Vila Nova De Gaia, Portugal, 4434 502
    • Novartis Investigative Site
• Singapore
  • Singapore, Singapore, 119228
    • Novartis Investigative Site
  • Singapore, Singapore, 169608
    • Novartis Investigative Site
• Slovakia
  • Slovak Republic
    • Kosice, Slovak Republic, Slovakia, 040 66
      • Novartis Investigative Site
• Spain
  • Madrid, Spain, 28046
    • Novartis Investigative Site
  • Andalucia
    • Granada, Andalucia, Spain, 18014
      • Novartis Investigative Site
  • Catalunya
    • Barcelona, Catalunya, Spain, 08036
      • Novartis Investigative Site
  • Murcia
    • El Palmar, Murcia, Spain, 30120
      • Novartis Investigative Site
  • Navarra
    • Pamplona, Navarra, Spain, 31008
      • Novartis Investigative Site
• Sweden
  • Goteborg, Sweden, 413 45
    • Novartis Investigative Site
  • Lund, Sweden, 221 85
    • Novartis Investigative Site
  • Stockholm, Sweden, 141 86
    • Novartis Investigative Site
• Switzerland
  • Bellinzona, Switzerland, 6850
    • Novartis Investigative Site
• Taiwan
  • Kaohsiung, Taiwan, 83301
    • Novartis Investigative Site
  • Taichung, Taiwan, 40447
    • Novartis Investigative Site
• United Kingdom
  • London, United Kingdom, W12 0NN
    • Novartis Investigative Site
  • Nottingham, United Kingdom, NG5
    • Novartis Investigative Site
  • Oxford, United Kingdom, OX3 7LJ
    • Novartis Investigative Site
• United States
  • Colorado
    • Longmont, Colorado, United States, 80501
      • Rocky Mountain Cancer Centers .
  • Florida
    • Fort Myers, Florida, United States, 33901
      • Florida Cancer Specialists Dept of Oncology (2)
    • Tallahassee, Florida, United States, 32308
      • Florida Cancer Specialists Pan .
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • University of Kentucky
  • Massachusetts
    • Worcester, Massachusetts, United States, 01655
      • Uni of Massachusetts Medical Center Dept of Oncology
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest Uni Baptist MC Comprehensive Cancer Ctr
  • Oregon
    • Eugene, Oregon, United States, 97401
      • Williamette Cancer Center
    • Portland, Oregon, United States, 97239
      • Oregon Health Sciences University .
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57105
      • Avera Cancer Avera Cancer Institute
  • Tennessee
    • Chattanooga, Tennessee, United States, 37404
      • Chattanooga Onc And Hem Assoc PC Tennessee Oncology Chattanooga
  • Texas
    • Dallas, Texas, United States, 75246
      • Texas Oncology Texas Onc - Amarillo
    • Dallas, Texas, United States, 75246
      • Texas Oncology-Baylor USO
    • Dallas, Texas, United States, 75246
      • Texas Oncology .
    • Dallas, Texas, United States, 75251
      • Texas Oncology Austin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Participants eligible for inclusion in this study must meet all of the following criteria:

  1. Male or female patients ≥ 18 years of age.
  2. Participants with CML-CP within 3 months of diagnosis.
  3. 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 109/L (≥ 100,000/mm3),

  • No evidence of extramedullary leukemic involvement, with the exception of hepatosplenomegaly.

    4. Eastern Cooperative Oncology Group (ECOG) performance status of 0,or 1. 5. Adequate end organ function as defined by:

  • Total bilirubin < 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 6. 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 7. Ability to provide written informed consent prior to any study related screening procedures being performed.

    8. 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:

1. 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.
2. Known cytopathologically confirmed CNS infiltration (in absence of suspicion of CNS involvement, lumbar puncture not required).

3. 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
4. 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
5. History of significant congenital or acquired bleeding disorder unrelated to cancer.
6. Major surgery within 4 weeks prior to study entry or who have not recovered from prior surgery.
7. 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
8. History of acute pancreatitis within 1 year prior to randomization or medical history of chronic pancreatitis.
9. History of chronic liver disease leading to severe hepatic impairment, or ongoing acute liver disease.

Other protocol-defined Inclusion/exclusion criteria will apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Asciminib; Patients will take asciminib 80 mg QD under fasting conditions on ongoing basis; Patients will be randomized 1:1 asciminib versus Investigator selected TKIs	Drug: Asciminib; Comes in 40 mg tablets and taken orally; Other Names: ABL001
Active Comparator: Investigator selected TKIs; Patients will take on ongoing basis the Investigator selected TKIs 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 a meal Bosotunib 400 mg QD administered with food	Drug: Imatinib; Comes in 100 mg and 400 mg tablets and taken orally; Other Names: STI571; Drug: Nilotinib; Comes in 150 mg capsules and taken orally; Other Names: AMN107; Drug: Bosutinib; Comes in 100 mg and 400 mg tablets and taken orally; Drug: Dasatinib; Comes in 70 mg and 100 mg tablets and taken orally

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Major Molecular Response (MMR) at week 48	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).	at 48 weeks (48 weeks after last patient first dose)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	at 96 weeks (96 weeks after last patient first dose)
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.	96 weeks after last patient first dose
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).	Planned total follow-up duration of 5 years
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).	Planned total follow-up duration of 5 years
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).	Planned total follow-up duration of 5 years
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).	Planned total follow-up duration of 5 years
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).	Planned total follow-up duration of 5 years
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).	Planned total follow-up duration of 5 years
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	Planned total follow-up duration of 5 years
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	Planned total follow-up duration of 5 years
Complete Cytogenic response (CCyR) at Week 48 & Week 96	The CCyR response status will be based on bone marrow assessment, in any patients who have this done due to a clinical indication	at 48 weeks and at 96 weeks (48 weeks and 96 weeks after last patient first dose)
Complete Cytogenic response (CCyR) by Week 48 & Week 96	The CCyR response status will be based on bone marrow assessment, in any patients who have this done due to a clinical indication	at 48 weeks and at 96 weeks (48 weeks and 96 weeks after last patient first dose)
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	Planned total follow-up duration of 5 years
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	Planned total follow-up duration of 5 years
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	Planned total follow-up duration of 5 years
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.	Planned total follow-up duration of 5 years
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.	Planned total follow-up duration of 5 years
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.	Planned total follow-up duration of 5 years
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.	Planned total follow-up duration of 5 years
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.	Planned total follow-up duration of 5 years
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) .	Planned total follow-up duration of 5 years
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.	Planned total follow-up duration of 5 years
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.	Planned total follow-up duration of 5 years
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.	Planned total follow-up duration of 5 years
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.	Planned total follow-up duration of 5 years
Trough plasma concentrations.	Trough plasma concentration will measure the concentration of asciminib in the blood immediately before the next dose is administered.	48 weeks after last patient first dose
Pharmacokinetics (PK) of Asciminib: Cmax	Cmax is the maximum serum concentration of asciminib during a dosing interval (mass x volume-1).	48 weeks after last patient first dose
PK of Asciminib: Tmax	Tmax is the time to reach maximum (peak) plasma drug concentration after dose administration (time)	48 weeks after last patient first dose
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)	48 weeks after last patient first dose
PK of Asciminib: CL/F	CL/F is the apparent total body clearance of asciminib from plasma after oral administration (volume x time-1).	48 weeks after last patient first dose
Change from baseline in overall scores and individual scales of the EORTC QLQ-C30	The European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-30) consists of functioning scales, symptoms' scales, single-item 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.	baseline, 48 weeks after last patient first dose, 96 weeks after last patient first dose
Change from baseline in overall scores and individual scales of the EORTC QLQ-CML24	The QLQ-CML24 consists of (i) 22 multi-scale items: impact on daily life, symptom burden, impact on worry/mood, satisfaction with care and information, (ii) 2 single items: body image problems, 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.	baseline, 48 weeks after last patient first dose, 96 weeks after last patient first dose

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals
• Investigators: Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): October 6, 2021
• Primary Completion (Actual): November 28, 2023
• Study Completion (Estimated): January 18, 2028

Study Registration Dates

• First Submitted: June 8, 2021
• First Submitted That Met QC Criteria: July 12, 2021
• First Posted (Actual): July 21, 2021

Study Record Updates

• Last Update Posted (Actual): March 25, 2024
• Last Update Submitted That Met QC Criteria: March 22, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Nilotinib; Chronic Myeloid Leukemia; CML; Imatinib; Bosutinib; Asciminib; Dasatinib; Philadelphia Chromosome; TKIs
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Disease Attributes; Bone Marrow Diseases; Hematologic Diseases; Myeloproliferative Disorders; Chromosome Aberrations; Translocation, Genetic; Chronic Disease; Leukemia; Leukemia, Myeloid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Philadelphia Chromosome; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Tyrosine Kinase Inhibitors; Imatinib Mesylate; Dasatinib; Nilotinib; Bosutinib; Asciminib
• Other Study ID Numbers: CABL001J12301; 2021-000678-27 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided are anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No