Study of Efficacy and Safety of Asciminib in Combination With Imatinib in Patients With Chronic Myeloid Leukemia in Chronic Phase (CML-CP) Who Have Been Previously Treated With Imatinib and Have Not Achieved Deep Molecular Response.

A Phase 2, Multi-center, Open-label, Randomized Study of Oral Asciminib Added to Imatinib Versus Continued Imatinib Versus Switch to Nilotinib in Patients With CML-CP Who Have Been Previously Treated With Imatinib and Have Not Achieved Deep Molecular Response

To evaluate efficacy, safety and pharmacokinetic profile of asciminib 40mg+imatinib or asciminib 60mg+imatinib versus continued imatinib and versus nilotinib in pre-treated patients with Chronic Myeloid Leukemia in chronic phase (CML-CP). An asciminib single agent arm (80 mg daily) was added after the primary analysis to evaluate if asciminib alone could lead to MR4.5 patients in Imatinib for at least one year who have never achieved deep molecular response (DMR).

Study Overview

• Status: Completed
• Conditions: Hematologic Diseases; Chronic Myelogenous Leukemia; CML; Leukemia, Myeloid Chronic
• Intervention / Treatment: Drug: Asciminib add-on; Drug: Imatinib; Drug: Nilotinib; Drug: Asciminib 80mg QD (asciminib single agent (ASAC))

Detailed Description

The study was a Phase 2, multi-center, open-label, randomized study of asciminib in two different doses (40 mg or 60 mg) in combination with imatinib 400 mg versus continued imatinib versus switch to nilotinib in participants with chronic myeloid leukemia in chronic phase (CML-CP) who had been previously treated with imatinib first line therapy for at least one year and had not achieved deep molecular response (DMR). Eligible participants were randomized 1:1:1:1 to receive asciminib 60 mg once daily (QD) as add-on therapy to imatinib 400 mg QD, or 40 mg QD as add-on therapy to imatinib 400 mg QD, or to continue imatinib 400 mg QD, or to switch to nilotinib 300 mg twice a day (BID). During the trial, there was no switch allowed. It was just at the moment of the randomization that the participants were selected to asciminib add-on arms or nilotinib.

Participants on the imatinib continuation arm who had not achieved MR4.5 at 48 weeks were allowed to cross-over ((CO) to receive the add-on treatment within 4 weeks after week 48 visit to receive the asciminib 60 mg combination add-on treatment, as this dose provided higher exposure. The cross-over was at the discretion of the investigator and the participant. Apart from a polymerase chain reaction (PCR) result of below MR4.5 at Week 48 visit, there were no other entry criteria for the cross-over part. Participants on nilotinib were not allowed to cross-over to receive the add-on treatment.

Participants on the study continued on the allocated treatment until treatment failure, intolerability, or for up to 96 weeks (in arms 1 to 4) after the last participant had received the first dose of treatment. After the last dose was received, every participant was followed up for safety for 30 days.

• Study Type: Interventional
• Enrollment (Actual): 104
• Phase: Phase 2

Contacts and Locations

Study Locations

• Austria
  • Vienna, Austria, 1140
    • Novartis Investigative Site
• Canada
  • Quebec
    • Montreal, Quebec, Canada, H1T 2M4
      • Novartis Investigative Site
• Czechia
  • Brno, Czechia, 625 00
    • Novartis Investigative Site
• Denmark
  • Copenhagen, Denmark, DK-2100
    • Novartis Investigative Site
• France
  • Bordeaux, France, 33076
    • Novartis Investigative Site
• Germany
  • Dresden, Germany, 01307
    • Novartis Investigative Site
• Italy
  • MI
    • Milan, MI, Italy, 20162
      • Novartis Investigative Site
  • RM
    • Roma, RM, Italy, 00161
      • Novartis Investigative Site
• Poland
  • Krakow, Poland, 31 531
    • Novartis Investigative Site
  • Warsaw, Poland, 00-791
    • Novartis Investigative Site
  • Wroclaw, Poland, 50 367
    • Novartis Investigative Site
• Portugal
  • Lisbon, Portugal, 1099-023
    • Novartis Investigative Site
  • Porto, Portugal, 4200-072
    • Novartis Investigative Site
• Russia
  • Moscow, Russia, 125167
    • Novartis Investigative Site
  • Moscow, Russia, 125284
    • Novartis Investigative Site
  • Saint Petersburg, Russia, 191024
    • Novartis Investigative Site
  • Saint Petersburg, Russia, 197341
    • Novartis Investigative Site
• South Korea
  • Seoul, South Korea, 06591
    • Novartis Investigative Site
  • Gyeonggi-do
    • Uijeongbu-si, Gyeonggi-do, South Korea, 11759
      • Novartis Investigative Site
• Spain
  • Madrid, Spain, 28034
    • Novartis Investigative Site
  • Seville, Spain, 41009
    • Novartis Investigative Site
  • Valencia, Spain, 46026
    • Novartis Investigative Site
  • Barcelona
    • Badalona, Barcelona, Spain, 08916
      • Novartis Investigative Site
• Taiwan
  • Changhua, Taiwan, 50006
    • Novartis Investigative Site
  • Taoyuan District, Taiwan, 33305
    • Novartis Investigative Site
• United Kingdom
  • Liverpool, United Kingdom, CH63 4JY
    • Novartis Investigative Site
  • London, United Kingdom, W12 0HS
    • Novartis Investigative Site
  • Oxford, United Kingdom, OX3 7LE
    • Novartis Investigative Site
• United States
  • Georgia
    • Augusta, Georgia, United States, 30912
      • Georgia Regents University
  • Maryland
    • Baltimore, Maryland, United States, 21205
      • Sidney Kimmel Comprehensive Cancer Center

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Male or female patients ≥ 18 years of age with a confirmed diagnosis of CML-CP.
• Minimum of one year (12 calendar months) treatment with imatinib first line for CML-CP (patients have to be on imatinib 400 mg QD at randomization and had no dose change in the past three months).

For Korea only:

(i) a minimum of one year (12 calendar months) of prior treatment with imatinib for patients with BCR::ABL1 levels > 0.1%, ≤ 1% IS at the time of randomization.

(ii) a minimum of two years (24 calendar months) of prior treatment with imatinib for patients with BCR::ABL 1 levels > 0.01%, ≤ 0.1% IS at the time of randomization.

• BCR::ABL1 levels > 0.01% IS (International Scale) and ≤ 1% IS at the time of randomization as confirmed with a central assessment at screening; patients must not have achieved deep molecular response (MR4 IS) confirmed by 2 consecutive tests at any time during prior imatinib treatment. An isolated, single test result with BCR::ABL1 levels < 0.01 % (MR4 IS) is allowed, however, it should not have been observed within the 9 months prior to randomization
• Patient must meet the following laboratory values before randomization:
• Absolute Neutrophil Count ≥ 1.5 x 10E9/L
• Platelets ≥ 75 x 10E9/L
• Hemoglobin ≥ 9 g/dL
• Serum creatinine < 1.5 mg/dL
• Total bilirubin ≤ 1.5 x ULN (Upper Limit of Normal) except for patients with Gilbert's syndrome who may only be included with total bilirubin ≤ 3.0 x ULN
• Aspartate transaminase (AST) ≤ 3.0 x ULN
• Alanine transaminase (ALT) ≤ 3.0 x ULN
• Alkaline phosphatase ≤ 2.5 x ULN
• Serum lipase ≤ 1.5 x ULN
• Participants must have the following laboratory values ≥ Lower Limit of Normal or corrected to within normal limits with supplements prior to randomization: potassium increase of up to 6.0 mmol/L is acceptable if associated with creatinine clearance within normal limits ; calcium increase of up to 12.5 mg/dl or 3.1 mmol/L is acceptable if associated with creatinine clearance* within normal limits) ; magnesium increase up to 3.0 mg/dL or 1.23 mmol/L if associated with creatinine clearance within normal limits.

Key Exclusion Criteria:

• Treatment failure according to European Leukemia Network (ELN) criteria 2013 during imatinib treatment.
• Known second chronic phase of CML after previous progression to Accelerated Phase (AP)/Blast Crisis (BC).
• Previous treatment with any tyrosine kinase inhibitors (TKIs) other than imatinib.
• History or current diagnosis of ECG abnormalities indicating significant risk or safety for participants participating in the study such as:
• History of myocardial infarction, angina pectoris, coronary artery bypass graft within 6 months prior to randomization
• Concomitant clinically significant arrhythmias
• Resting QTcF ≥ 450 msec (male) or ≥ 460 msec (female) prior to randomization

• 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
  • Concomitant medications with a "known" risk of Torsades de Pointes
  • inability to determine the QTcF interval 5. 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 clinically significant hyperlipidemia and high serum amylase) 6. History of acute pancreatitis within 1 year prior to randomization or medical history of chronic pancreatitis; on-going acute liver disease or history of chronic liver disease 7. History of other active malignancy within 3 years prior to randomization with the exception of basal cell skin cancer, indolent prostate cancer and carcinoma in situ treated curatively.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Asciminib 60mg QD + Imatinib 400mg QD; Asciminib 60 mg taken once daily in combination with Imatinib 400 mg taken once daily	Drug: Asciminib add-on; Asciminib was supplied as 40 mg and 20 mg tablets and taken orally once daily.; Other Names: ABL001 (asciminib); Drug: Imatinib; Imatinib was supplied as 400 mg and 100 mg tablets and taken orally once daily.; Other Names: STI571
Experimental: Asciminib 40mg QD + Imatinib 400mg QD; Asciminib 40 mg taken once daily in combination with Imatinib 400 mg taken once daily	Drug: Asciminib add-on; Asciminib was supplied as 40 mg and 20 mg tablets and taken orally once daily.; Other Names: ABL001 (asciminib); Drug: Imatinib; Imatinib was supplied as 400 mg and 100 mg tablets and taken orally once daily.; Other Names: STI571
Active Comparator: Imatinib 400mg QD; Imatinib 400 mg taken once daily	Drug: Imatinib; Imatinib was supplied as 400 mg and 100 mg tablets and taken orally once daily.; Other Names: STI571
Active Comparator: Nilotinib 300mg BID; Nilotinib 300 mg taken twice daily	Drug: Nilotinib; Nilotinib was supplied as 150 mg and 200 mg hard gelatin capsules and taken orally twice daily.; Other Names: AMN107
Experimental: Asciminib 80mg QD (ASAC); Asciminib 80 mg taken once daily	Drug: Asciminib 80mg QD (asciminib single agent (ASAC)); Asciminib was supplied as 40 mg and 20 mg tablets and taken orally once daily (in the fasted state) on a continuous schedule (QD).; Other Names: ABL001

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Molecular Response (MR)^4.5 Rate at 48 Weeks and Difference in Rate Between Asciminib + Imatinib and Imatinib Alone	Percentage of participants still treated with the randomized treatment at 48 weeks and are in MR^4.5 (BCR::ABL1 ratio of ≤ 0.0032%) at 48 weeks (± assessment window), among all participants in the asciminib add-on arms vs imatinib arm.	at Week 48

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of MR^4.5 at 48 Weeks (Asciminib add-on Arms vs Nilotinib)	Percentage of participants in MR^4.5 (BCR::ABL1 ratio of ≤ 0.0032%) at 48 weeks in asciminib add-on arms vs nilotinib arm.	at Week 48
Rate of MR^4.5 by 48 Weeks (Randomized Arms)	Best observed MR^4.5 rate (BCR::ABL1 ratio of ≤ 0.0032%) up to 48 weeks, i.e. the percentage of participants who achieved MR 4.5 anytime up to 48 weeks.	by 48 weeks
Rate of MR^4.5 at 96 Weeks (Randomized Arms) and Difference in Rate Between Asciminib + Imatinib and Nilotinib Alone	Percentage of participants in MR^4.5 (BCR::ABL1 ratio of ≤ 0.0032%) at 96 weeks in asciminib add-on arms vs nilotinib arm.	at Week 96
Rate of MR^4.5 by 96 Weeks (Randomized Arms)	Best observed MR^4.5 (BCR::ABL1 ratio of ≤ 0.0032%) rate up to 96 weeks, i.e. the percentage of participants who achieved MR^4.5 anytime up to 96 weeks.	by 96 weeks
Sustained MR^4.5 From at 96 Weeks (Randomized Arms)	Sustained MR^4.5 (BCR::ABL1 ratio of ≤ 0.0032%) rate was defined as the percentage of participants who were in MR4.5 at 48 weeks and 96 weeks and who had no loss of MR4.5 in between those 2 time points.	at 96 weeks
Time to MR^4.5 (Randomized Arms)	Time to MR^4.5 is the time from first dose to first MR^4.5 (BCR::ABL1 ratio of ≤ 0.0032%) computed only for participants who achieved MR^4.5 at least once before the cut-off date.	96 weeks after the last participant received the first study dose
Duration of MR^4.5 (Randomized Arms)	Duration of MR^4.5 was defined as the time from the first documented MR^4.5 and the end date of MR^4.5, i.e., the earliest date of loss of MR^4.5 or CML-related death. Confirmed loss of MR^4.5 is defined as an increase of the BCR::ABL1 ratio to >0.0032% in two consecutive blood samples, by International Scale.	96 weeks after the last participant received the first study dose
Pharmacokinetic Profile of Asciminib 40/60 mg and Imatinib When Administered in Combination - Cmax (Randomized Arms)	The maximum (peak) observed plasma, blood, serum, or other body fluid drug concentration after single dose administration (mass x volume-1).	Week 2 Day 14: pre-dose (0h), 1h, 2h, 3hr 4h and 8h post-dose; Week 4 Day 28: pre-dose (0h) 2h, 3h, 4h post-dose
Pharmacokinetic Profile of Asciminib 40/60 mg and Imatinib When Administered in Combination - Tmax (Randomized Arms)	The time to reach maximum (peak) plasma, blood, serum, or other body fluid drug concentration after single dose administration (time).	Week 2 Day 14: pre-dose (0h), 1h, 2h, 3hr 4h and 8h post-dose; Week 4 Day 28: pre-dose (0h) 2h, 3h, 4h post-dose
Pharmacokinetic Profile of Asciminib 40/60 mg and Imatinib When Administered in Combination - Cmin (Randomized Arms)	Minimum drug plasma(serum/blood) concentration	Week 2 Day 14: pre-dose (0h), Week 4 Day 28: pre-dose (0h)
Pharmacokinetic Profile of Asciminib 40/60 mg and Imatinib When Administered in Combination - AUClast (Randomized Arms)	The AUC from time zero to the last measurable concentration sampling time (Tlast) (mass x time x volume-1).	Week 2 Day 14: pre-dose (0h), 1h, 2h, 3hr 4h and 8h post-dose
Pharmacokinetic Profile of Asciminib 40/60 mg and Imatinib When Administered in Combination - AUCtau (Randomized Arms)	The AUC calculated to the end of a dosing interval (tau) at steady-state	Week 2 Day 14: pre-dose (0h), 1h, 2h, 3hr 4h and 8h post-dose
Molecular Response (MR) 4.5 Rate at 48 Weeks (Asciminib Single Agent Cohort (ASAC))	Percentage of participants on asciminib 80 mg QD with MR^4.5 (BCR::ABL1 ratio of ≤ 0.0032%) at 48 weeks.	at Week 48
Time to MR^4.5 (ASAC)	Time from first dose of asciminib 80 mg QD to first MR^4.5 (BCR::ABL1 ratio of ≤ 0.0032%) computed only for participants who achieved MR^4.5.	48 weeks after the last enrolled participant (asciminib 80 mg cohort) received the first study dose
Duration of MR^4.5 (ASAC)	Time from first MR^4.5 (BCR::ABL1 ratio of ≤ 0.0032%) until confirmed loss of MR^4.5 or CML-related death.	48 weeks after the last enrolled participant (asciminib 80 mg cohort) received the first study dose
Pharmacokinetic Profile of Asciminib 80mg QD - Cmax (ASAC)	The maximum (peak) observed plasma drug concentration after oral dose administration (mass x volume-1).	Week 2 Day 14: 0h (pre-dose), 1h, 2h, 3h, 4h, 8h post-dose; Week 4 Day 28: 0h (pre-dose), 2h, 3h, 4h post-dose
Pharmacokinetic Profile of Asciminib 80mg QD - Tmax (ASAC)	The time to reach maximum (Cmax) plasma drug concentration after oral dose administration (time).	Week 2 Day 14: 0h (pre-dose), 1h, 2h, 3h, 4h, 8h post-dose; Week 4 Day 28: 0h (pre-dose), 2h, 3h, 4h post-dose
Pharmacokinetic Profile of Asciminib 80mg QD - Cmin (ASAC)	Minimum drug plasma (serum/blood) concentration	Week 2 Day 14: 0h (pre-dose), Week 4 Day 28: 0h (pre-dose)
Pharmacokinetic Profile of Asciminib 80mg QD - AUClast (ASAC)	The AUC from time zero to the last measurable concentration sampling time (Tlast) (mass x time x volume-1).	Week 2 Day 14: 0h (pre-dose), 1h, 2h, 3h, 4h, 8h post-dose
Pharmacokinetic Profile of Asciminib 80mg QD - AUCtau (ASAC)	The AUC calculated to the end of a dosing interval (tau) at steady-state (amount x time x volume-1)	Week 2 Day 14: 0h (pre-dose), 1h, 2h, 3h, 4h, 8h post-dose

Collaborators and Investigators

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

Publications and helpful links

General Publications

• Hughes TP, Saglio G, Geissler J, Kim DW, Lomaia E, Mayer J, Turkina A, Kapoor S, Cardoso AP, Nieman B, Quenet S, Cortes JE. Asciminib add-on to imatinib demonstrates sustained high rates of ongoing therapy and deep molecular responses with prolonged follow-up in the ASC4MORE study. J Hematol Oncol. 2024 Dec 18;17(1):125. doi: 10.1186/s13045-024-01642-6.

Study record dates

Study Major Dates

• Study Start (Actual): November 22, 2018
• Primary Completion (Actual): November 8, 2021
• Study Completion (Actual): February 26, 2025

Study Registration Dates

• First Submitted: June 15, 2018
• First Submitted That Met QC Criteria: July 3, 2018
• First Posted (Actual): July 6, 2018

Study Record Updates

• Last Update Posted (Actual): April 21, 2026
• Last Update Submitted That Met QC Criteria: April 17, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: tyrosine kinase inhibitor; Nilotinib; Hematologic Diseases; CML; Imatinib; leukemia; Chronic Myelogenous Leukemia; Asciminib; ABL001; cancer of the white blood cells; chronic phase; leukemia, myeloid chronic; deep molecular response; DMR; Ph+ CML; leukemia, myeloid; CML with Ph+
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Chronic Disease; Disease Attributes; Neoplasms by Histologic Type; Bone Marrow Diseases; Myeloproliferative Disorders; Pathological Conditions, Signs and Symptoms; Hemic and Lymphatic Diseases; Leukemia; Leukemia, Myeloid; Hematologic Diseases; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Hydrocarbons; Hydrocarbons, Cyclic; Carboxylic Acids; Hydrocarbons, Aromatic; Amides; Pyrimidines; Benzene Derivatives; Acids, Carbocyclic; Benzoates; Benzamides; Piperazines; Imatinib Mesylate; nilotinib; asciminib
• Other Study ID Numbers: CABL001E2201; 2018-001594-24 (EudraCT Number); 2024-515040-23-00 (Other Identifier: EU CTIS)

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 expert 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 is currently available according to the 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