Asciminib Treatment Optimization in ≥ 3rd Line CML-CP

A Phase 3b, Multi-center, Open-label, Treatment Optimization Study of Oral Asciminib in Patients With Chronic Myelogenous Leukemia in Chronic Phase (CML-CP) Previously Treated With 2 or More Tyrosine Kinase Inhibitors

The purpose of the study is to optimize the treatment of asciminib in patients with chronic myelogenous leukemia in chronic phase (CML-CP) previously treated with 2 or more Tyrosine Kinase Inhibitors (TKIs).

Study Overview

• Status: Completed
• Conditions: Chronic Myelogenous Leukemia
• Intervention / Treatment: Drug: ABL001 40mg BID; Drug: ABL001 80mg QD; Drug: ABL001 200mg QD

Detailed Description

This study consists of a screening period of up to 28 days, a treatment period of 144 weeks and a post-treatment safety follow-up period of 4 weeks.

Patients will receive asciminib as study treatment continuously for up to 144 weeks or until disease progression, treatment failure or intolerance to treatment. At treatment initiation, asciminib will be provided to all trial patients at a total daily dose of 80 mg. All patients will be randomly assigned 1:1 to 2 groups with 80 mg given either as 40 mg b.i.d. or 80 mg q.d., using IRT to avoid any selection bias.

In patients not achieving Major Molecular Responses (MMR) at 48 weeks or losing the response after the week 48 assessment up to week 108, asciminib dose may be escalated to 200 mg q.d. if in the investigator's opinion the patient may benefit from the escalation. In addition, there must not be any grade 3 or 4 toxicity while on therapy, or persistent grade 2 toxicity, possibly related to asciminib and unresponsive to optimal management.

The trial will enroll a total of approximately 186 patients:

• 156 patients with CML-CP not in MMR at baseline who were treated with two or more TKIs and who were either resistant (ELN 2020 warning or failure) or intolerant to the last treatment will be enrolled. For this population, the primary endpoint for MMR at 48 weeks will be assessed.
• Up to 30 additional patients intolerant only to their last TKI treatment and in MMR at baseline will also be enrolled. This patient population will not be part of primary endpoint analysis; however, all assessments will be done as with the 156 patients from the population of the primary endpoint analysis.

• Study Type: Interventional
• Enrollment (Actual): 199
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1114AAN
    • Novartis Investigative Site
  • Buenos Aires
    • CABA, Buenos Aires, Argentina, C1221ADC
      • Novartis Investigative Site
• Austria
  • Graz, Austria, 8036
    • Novartis Investigative Site
  • Linz, Austria, 4010
    • Novartis Investigative Site
  • Vienna, Austria, 1140
    • Novartis Investigative Site
• Brazil
  • São Paulo, Brazil, 01227-200
    • Novartis Investigative Site
  • Rio de Janeiro
    • Rio de Janeiro, Rio de Janeiro, Brazil, 20211-030
      • Novartis Investigative Site
• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 1M9
      • Novartis Investigative Site
  • Ontario
    • Toronto, Ontario, Canada, M5G 2M9
      • Novartis Investigative Site
• France
  • Bordeaux, France, 33076
    • Novartis Investigative Site
  • Lyon, France, 69373
    • Novartis Investigative Site
  • Montpellier, France, 34295
    • Novartis Investigative Site
  • Nantes, France, 44093
    • Novartis Investigative Site
  • Paris, France, 75475
    • Novartis Investigative Site
• Germany
  • Berlin, Germany, 13353
    • Novartis Investigative Site
  • Kiel, Germany, 24116
    • Novartis Investigative Site
  • München, Germany, 80377
    • Novartis Investigative Site
  • Baden-Wurttemberg
    • Mannheim, Baden-Wurttemberg, Germany, 68305
      • Novartis Investigative Site
  • Hesse
    • Frankfurt am Main, Hesse, Germany, 60590
      • Novartis Investigative Site
  • Thuringia
    • Jena, Thuringia, Germany, 07740
      • Novartis Investigative Site
• Greece
  • Athens, Greece, 115 27
    • Novartis Investigative Site
  • Thessaloniki, Greece, 570 10
    • Novartis Investigative Site
• Italy
  • MB
    • Monza, MB, Italy, 20900
      • Novartis Investigative Site
  • RM
    • Roma, RM, Italy, 00161
      • Novartis Investigative Site
  • VR
    • Verona, VR, Italy, 37134
      • Novartis Investigative Site
• Malaysia
  • Johor Bahru, Malaysia, 80100
    • Novartis Investigative Site
  • Kuala Selangor, Malaysia, 68000
    • Novartis Investigative Site
  • Pulau Pinang
    • George Town, Pulau Pinang, Malaysia, 10450
      • Novartis Investigative Site
  • Sabah
    • Kota Kinabalu, Sabah, Malaysia, 88586
      • Novartis Investigative Site
• Oman
  • Khoudh, Oman, 123
    • Novartis Investigative Site
• Poland
  • Katowice, Poland, 40-519
    • Novartis Investigative Site
  • Warsaw, Poland, 00-791
    • Novartis Investigative Site
• Singapore
  • Singapore, Singapore, 119074
    • Novartis Investigative Site
  • Singapore, Singapore, 169608
    • Novartis Investigative Site
• South Korea
  • Seoul, South Korea, 06351
    • Novartis Investigative Site
  • Taegu, South Korea, 41944
    • Novartis Investigative Site
  • Korea
    • Seoul, Korea, South Korea, 03080
      • Novartis Investigative Site
• Spain
  • Barcelona, Spain, 08035
    • Novartis Investigative Site
  • Madrid, Spain, 28041
    • Novartis Investigative Site
  • A Coruna
    • Santiago Compostela, A Coruna, Spain, 15706
      • Novartis Investigative Site
  • Bizkaia
    • Bilbao, Bizkaia, Spain, 48013
      • Novartis Investigative Site
  • Santa Cruz De Tenerife
    • Santa Cruz, Santa Cruz De Tenerife, Spain, 38009
      • Novartis Investigative Site
• United Kingdom
  • Cambridge, United Kingdom, CB2 0QQ
    • Novartis Investigative Site
  • London, United Kingdom, SE1 9RT
    • Novartis Investigative Site
  • London, United Kingdom, W12 0HS
    • Novartis Investigative Site
  • West Yorkshire
    • Leeds, West Yorkshire, United Kingdom, LS9 7TF
      • Novartis Investigative Site
• Vietnam
  • Hanoi, Vietnam, 100000
    • Novartis Investigative Site
  • Ho Chi Minh City, Vietnam, 70000
    • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion criteria:

• Signed informed consent must be obtained prior to participation in the study
• Male or female patients with a diagnosis of CML-CP ≥ 18 years of age
• Treatment with a minimum of 2 or more prior TKIs (i.e. imatinib, nilotinib, dasatinib, bosutinib, radotinib or ponatinib)
• Warning or failure (adapted from the 2020 ELN Recommendations) or intolerance to the most recent TKI therapy at the time of screening
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0, 1, or 2
• Adequate end organ function (as per central laboratory tests)

Key Exclusion criteria:

• Known presence of the BCR::ABL1 T315I mutation at any time prior to study entry
• Known second chronic phase of CML after previous progression to AP/BC
• Previous treatment with a hematopoietic stem-cell transplantation
• Patient planning to undergo allogeneic hematopoietic stem cell transplantation
• Uncontrolled cardiac repolarization abnormality
• 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
• History of acute pancreatitis within 1 year of study entry or past medical history of chronic pancreatitis
• Testing for Hepatitis B surface antigen (HbsAg) and Hepatitis B core antibody (HBcAb / anti HBc) will be performed at screening. Patients with active Hepatitis B Virus (HBV) infection (hepatitis B surface antigen [HbsAg] positive) will be excluded

Other Inclusion/Exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ABL001; Participants will be treated with 80 mg of ABL001 (40 mg BID or 80mg QD). In patients not achieving MMR at 48 weeks or losing the response after the week 48 assessment up to week 108, asciminib dose may be escalated to 200 mg q.d. if in the investigator's opinion the patient may benefit from the escalation.	Drug: ABL001 40mg BID; One tablet of 40 mg will be taken orally twice a day (BID); Other Names: asciminib; Drug: ABL001 80mg QD; Two tablets of 40 mg will be taken orally once a day (QD); Other Names: asciminib; Drug: ABL001 200mg QD; Five tablets of 40 mg will be taken orally once a day (QD); Other Names: asciminib

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MMR Rate at Week 12, 24, 36, 72, 96 and 144 for Patients With no MMR at Baseline	The Major Molecular Response (MMR) rate at alternative time points (weeks 12, 24, 36, 72, 96 and 144) for all patients with no evidence of MMR at baseline refers to the percentage of patients who achieve MMR after those respective weeks of treatment, despite not having MMR at the start. MMR itself is defined as achieving a BCR::ABL1 ratio of ≤ 0.1%.	Week 12, 24, 36, 72, 96 and 144
Major Molecular Response (MMR) Rate at Week 48 for Patients With MMR at Baseline	The Major Molecular Response (MMR) rate at Week 48 for patients with MMR at baseline refers to the percentage of patients who maintain or achieve MMR after 48 weeks of treatment. MMR itself is defined as achieving a BCR::ABL1 ratio of ≤ 0.1%.	Week 48.
Time to MMR for Subjects Without MMR at Baseline	Time to MMR defined as the time from the date of randomization to the date of the first documented MMR. MMR itself is defined as achieving a BCR::ABL1 ratio of ≤ 0.1%.	From the date of enrollment to the date of first documented MMR, assessed up to 144 weeks
Rate of BCR::ABL1 ≤ 10% for Subjects Without MMR at Baseline	The rate of BCR::ABL1 ≤ 10% refers to the percentage of patients who achieve a BCR::ABL1 level of 10% or lower within the first 48 weeks of treatment.	Week 12, 24, 36 and 48
Rate of BCR::ABL1 ≤ 1% for Subjects Without MMR at Baseline	The rate of BCR::ABL1 ≤ 1% refers to the percentage of patients who achieve a BCR::ABL1 level of 1% or lower within the first 48 weeks of treatment.	Week 12, 24, 36 and 48.
Deep Molecular Responses (MR4) Rate for Subjects Without MMR at Baseline	Deep molecular responses (MR4) is defined as a ≥ 4 log reduction in BCR::ABL1 transcripts compared to the standardized baseline, equivalent to 0.01% BCR::ABL1/ABL1 by the international scale (IS).	Week 12, 24, 36, 48, 72, 96 and 144.
Deep Molecular Responses (MR4.5) Rate for Subjects Without MMR at Baseline	Deep molecular responses (MR4.5) is defined as a ≥ 4.5 log reduction in BCR::ABL1 transcripts compared to the standardized baseline, equivalent to 0.0032% BCR::ABL1/ABL1 by the international scale (IS).	Week 12, 24, 36, 48, 72, 96 and 144.
Rate of Complete Cytogenetic Response (CCyR) for Subjects Without MMR at Baseline	Cytogenetic Response is assessed based on the percentage of Philadelphia chromosome-positive (Ph+) metaphases in the bone marrow, with a review of at least 20 metaphases required. Complete Cytogenetic Response (CCyR) is defined as 0% Ph+ metaphases in the bone marrow.	Week 48 and end of treatment (up to 144 weeks)
Occurrence of High-risk Additional Chromosomal Abnormalities (ACA) for Subjects Without MMR at Baseline	High-risk additional chromosomal abnormalities (ACAs) are specific chromosomal abnormalities that are considered to increase the risk in Philadelphia chromosome-positive (Ph+) cells.	Up to 144 weeks
Cumulative Molecular Response Rate of BCR::ABL1 ≤ 10% for Subjects Without MMR at Baseline	The cumulative molecular response rate refers to the proportion of subjects achieving a BCR::ABL1 level of ≤ 10% on the international scale (IS) over a specified period.	From enrollment to end of treatment up to 144 weeks.
Cumulative Molecular Response Rate of BCR::ABL1 ≤1% for Subjects Without MMR at Baseline	The cumulative molecular response rate refers to the proportion of subjects achieving a BCR::ABL1 level of ≤ 1% on the international scale (IS) over a specified period.	From enrollment to end of treatment up to 144 weeks.
Cumulative Molecular Response Rate of MMR for Subjects Without MMR at Baseline	The cumulative molecular response rate refers to the proportion of subjects achieving MMR, defined as a BCR::ABL1 ratio of ≤ 0.1% on the international scale (IS), over a specified period.	From enrollment to end of treatment up to 144 weeks.
Cumulative Molecular Response Rate of MR4 for Subjects Without MMR at Baseline	The cumulative molecular response rate refers to the proportion of subjects achieving MR4, defined as a ≥ 4 log reduction in BCR::ABL1 transcripts compared to the standardized baseline, equivalent to 0.01% BCR::ABL1/ABL1 by the international scale (IS), over a specified period.	From enrollment to end of treatment up to 144 weeks.
Cumulative Molecular Response Rate of MR4.5 for Subjects Without MMR at Baseline	The cumulative molecular response rate refers to the proportion of subjects achieving MR4.5, defined as a ≥ 4.5 log reduction in BCR::ABL1 transcripts compared to the standardized baseline, equivalent to 0.0032% BCR::ABL1/ABL1 by the international scale (IS), over a specified period.	From enrollment to end of treatment up to 144 weeks.
Duration of MMR	Duration of MMR is defined as the time from the date of first documented MMR to the earliest date of loss of MMR, progression to accelerated phase (AP) or blast crisis (BC), or CML-related death. The duration of MMR is analyzed for the subjects in FAS who achieved MMR at any time.	From the date of the first documented molecular response at MMR level to the date of first documented loss of the response level or death due to any cause, whichever occurs first, assessed up to 144 weeks.
Duration of MR4 Without Loss of MMR	Duration of MR4 without loss of MMR refers to the period during which a patient maintains a deep molecular response (MR4) without experiencing a loss of Major Molecular Response (MMR).	From the date of first documented MR4 without loss of MMR to the date of first documented loss of the response level or death due to any cause, whichever occurs first, assessed up to 144 weeks.
Progression-Free Survival (PFS) for Subjects Without MMR at Baseline	Progression-Free Survival (PFS) is defined as the time from the date of randomization to the earliest occurrence of documented disease progression to AP/BC or the date of death from any cause, assessed up to approximately 144 weeks. The time will be censored at the date of last study assessment (PCR, cytogenetic, hematologic or extramedullary) or last post-treatment follow-up for subjects without event. PFS (in months) is calculated as: (date of disease progression/death or censoring date - date of randomization +1)/30.4375.	Up to 144 weeks.
Overall Survival (OS) for Subjects Without MMR at Baseline	Overall Survival (OS) is defined as the time from treatment assignment to death due to any cause during study, assessed up to 144 weeks. Subjects who are alive at the time of the analysis data cutoff date will be censored at the date of last contact before the cut-off date. OS (in months) is calculated as: (date of death or censoring date - date of randomization + 1)/30.4375.	Up to 144 weeks.
Time to Treatment Failure (TTF) for Subjects Without MMR at Baseline	Time from treatment assignment to treatment failure is defined as BCR-ABL1>10%, assessed up to 144 weeks. For subjects who have not reached treatment failure, their TTFs will be censored at the time of last study assessment (PCR, cytogenetic, hematologic or extramedullary) before the cut-off date. TTF (in months) is calculated as: (date of treatment failure or censoring date - date of randomization + 1)/30.4375.	Up to 144 weeks.
Change in Symptom Burden and Interference From Baseline Over Time According to the MDASI-CML PRO Instrument	The MD Anderson Symptom Inventory - Chronic Myeloid Leukemia (MDASI-CML) is a 26 item self-administered questionnaire for adult CML patients. Twenty of the items measure the severity of disease-related symptoms (symptom burden) and are scored from 0 (not present) to 10 (as bad as you can imagine) and 6 items that measure symptom interference with daily life (interference) scored from 0 (did not interfere) to 10 (interfered completely). For symptom burden, total scores range from 0 to 200 and for interference range from 0 to 60, with higher scores indicates high impact on severity of chronic myeloid leukemia-related symptoms and on impact of these symptoms on daily functioning for the patient.	Week 4, 12, 24, 48, 72, 96, 120 and at end of treatment (up to 144 weeks).

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): October 13, 2021
• Primary Completion (Actual): March 12, 2024
• Study Completion (Actual): February 25, 2026

Study Registration Dates

• First Submitted: June 28, 2021
• First Submitted That Met QC Criteria: June 28, 2021
• First Posted (Actual): July 1, 2021

Study Record Updates

• Last Update Posted (Actual): March 18, 2026
• Last Update Submitted That Met QC Criteria: March 4, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: tyrosine kinase inhibitor; Phase 3; Asciminib; ABL001; Chronic myelogenous leukemia (CML); chronic myeloid leukemia (CML); chronic myelocytic leukemia (CML); chronic granulocytic leukemia (CGL); cancer of the white blood cells; clonal bone marrow stem cell disorder; proliferation of mature granulocytes; Treatment optimization; European Leukemia Network (ELN) Recommendations 2020; Major Molecular Response (MMR) rate at 48 weeks
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Chronic Disease; Disease Attributes; Neoplasms by Histologic Type; Hematologic Diseases; Leukemia, Myeloid; Bone Marrow Diseases; Leukemia; Myeloproliferative Disorders; Pathological Conditions, Signs and Symptoms; Hemic and Lymphatic Diseases; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Tyrosine Kinase Inhibitors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; Micronutrients; Vitamin B Complex; Vitamins; BID protein, human; asciminib
• Other Study ID Numbers: CABL001A2302; 2024-511381-36-00 (Ctis: EU CT 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 is 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: No
• Studies a U.S. FDA-regulated device product: No