Asciminib Monotherapy, With Dose Escalation, for 2nd and 1st Line Chronic Myelogenous Leukemia (ASC2ESCALATE)

A Phase II Multicenter, Open-label, Single-arm Dose Escalation Study of Asciminib Monotherapy in 2nd and 1st Line Chronic Phase - Chronic Myelogenous Leukemia (ASC2ESCALATE)

This will be a multicenter Phase II open-label study of asciminib in CML-CP patients who have been previously treated with one prior ATP- binding site TKI with discontinuation due to treatment failure, warning or intolerance. (2L patient cohort). In addition, newly diagnosed CML-CP patients who may have received up to 4 weeks of prior TKI are included in a separate 1L patient cohort.

Study Overview

• Status: Active, not recruiting
• Conditions: Chronic Myelogenous Leukemia - Chronic Phase
• Intervention / Treatment: Drug: asciminib

Detailed Description

This trial consists of three periods: screening and baseline for up to 28 days, active treatment for up to 156 weeks and a safety follow up period for 30 days.

Ninety-two (92) 2L patients with CML-CP without T315I mutation who had 1 prior ATP-binding site TKI discontinued due to treatment failure, warning or intolerance will be considered for the current study. Patients will be tested at screening for the T315I mutation and excluded if the mutation is found.

To gain additional insights into the effect of asciminib in the 1L setting, an additional cohort of newly diagnosed CML-CP patients will be enrolled in the study. Based on the number of participating sites, it is approximated that between 60 and 90 patients could be enrolled. Enrollment of the 1L cohort will be stopped when a maximum of 90 patients have been enrolled or when approximately 60 patients have been enrolled and the 2L cohort is fully recruited, whichever comes first.

Informed consent will be obtained before any procedures are performed for the study including eligibility assessments.

All eligible patients will be initially treated with asciminib at 80 mg QD. At 6 months of study treatment, patients who have achieved BCR-ABL1IS ≤1% will continue on the same dose whereas those who have not will increase dose to 200mg QD.

At 12 months of study treatment, patients will be evaluated for the primary endpoint of the study (MMR at 12 month in 2L patient cohort) and will pursue one of the following:

• Continue on the current dose of asciminib if MMR is achieved
• Increase dose to 200 mg QD if on 80 mg QD dosing and MMR is not achieved
• Increase dose to 200 mg BID if on 200 mg QD dosing and MMR is not achieved
• Take the patient off the study and switch to Investigator's agent of choice if MMR is not achieved and it is in the interest of the patient based on investigator's clinical judgment of prospect treatment benefit.

• Study Type: Interventional
• Enrollment (Actual): 34
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233-0271
      • University of Alabama at Birmingham
  • Alaska
    • Anchorage, Alaska, United States, 99508
      • Alaska Oncology and Hematology
  • Arizona
    • Scottsdale, Arizona, United States, 85258
      • City of Hope Phoenix
    • Tucson, Arizona, United States, 85711
      • USO Arizona Oncology
  • California
    • Cerritos, California, United States, 90703
      • Onco Inst of Hope and Innovation
    • Duarte, California, United States, 91010
      • City of Hope National Medical
    • Fresno, California, United States, 93701
      • UCSF Fresno Internal Medicine
    • Fullerton, California, United States, 92835
      • Virginia K Crosson Cancer Center
    • Los Angeles, California, United States, 90095
      • UCLA
    • Oakland, California, United States, 94609
      • Alta Bates Summit Medical Center
    • Torrance, California, United States, 90509-2910
      • Lundquist Inst BioMed at Harbor
  • Colorado
    • Boulder, Colorado, United States, 80304
      • Rocky Mountain Cancer Centers
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Yale University School of Medicine
    • Stamford, Connecticut, United States, 06904
      • The Stamford Hospital
  • Florida
    • Fort Myers, Florida, United States, 33901
      • Florida Cancer Specialists
    • Jacksonville, Florida, United States, 32207
      • Baptist MD Anderson Cancer Center
    • St. Petersburg, Florida, United States, 33705
      • Florida Cancer Specialists-North
    • Stuart, Florida, United States, 34994
      • Florida Cancer Specialists East
  • Georgia
    • Atlanta, Georgia, United States, 30033
      • City of Hope Atlanta
    • Atlanta, Georgia, United States, 30308
      • Emory University School of Medicine Winship Cancer Institute
    • Augusta, Georgia, United States, 30912
      • Augusta University Georgia
    • Marietta, Georgia, United States, 30060
      • Northwest Georgia Oncology Center
  • Indiana
    • Indianapolis, Indiana, United States, 42637
      • Franciscan Health Indianapolis
    • Indianapolis, Indiana, United States, 46260
      • Investigative Clinicl Rsrch of Indi
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • Holden Comp Can Cent Quad Cities U
  • Kansas
    • Wichita, Kansas, United States, 67214
      • Wichita Community Clcl Onco Program
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • University of Kentucky
  • Louisiana
    • Shreveport, Louisiana, United States, 71130
      • Louisiana State University
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana Farber Cancer Center
  • Michigan
    • Detroit, Michigan, United States, 48202-2689
      • Henry Ford Hospital
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • Jackson Onc Associates
  • Missouri
    • Columbia, Missouri, United States, 65203
      • University Missouri Ellis Fischel Cancer Center
    • St Louis, Missouri, United States, 63110
      • Siteman Cancer Center
  • Montana
    • Billings, Montana, United States, 59102
      • St Vincent Frontier Cancer Center
  • Nebraska
    • Lincoln, Nebraska, United States, 68506
      • Nebraska Hematology Oncology P C
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Dartmouth Hitchcock Medical Center
  • New Jersey
    • Clifton, New Jersey, United States, 07013
      • Care Access Research Clifton
    • Edison, New Jersey, United States, 88837
      • Hackensack Meridian Health
    • Hackensack, New Jersey, United States, 07601
      • Hackensack University Medical Ctr
    • New Brunswick, New Jersey, United States, 08901
      • Rutgers Cancer Institute of Nj
  • New Mexico
    • Albuquerque, New Mexico, United States, 87102
      • UNM
  • New York
    • Lake Success, New York, United States, 11042
      • Clinical Research Alliance
    • Mineola, New York, United States, 11501
      • NYU Langone Long Island
    • New York, New York, United States, 10029-6574
      • Mt Sinai Medical Center
    • New York, New York, United States, 10016
      • Manhattan Hematol Oncol Associates
    • Port Jefferson, New York, United States, 11776
      • New York Bld And Cancer Specialists
    • Stony Brook, New York, United States, 11794-8174
      • SUNY Stony Brook Medical Oncology
    • Syracuse, New York, United States, 13210
      • SUNY Upstate Medical Center
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27514
      • University of North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Novant Health Heart Vas Inst
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest Uni Health Sci
  • Ohio
    • Canton, Ohio, United States, 44718
      • Gabrail Cancer Center
    • Cincinnati, Ohio, United States, 45236
      • Hematology Oncology Care
    • Columbus, Ohio, United States, 43210
      • James Cancer Hospital and Solove Research Institute Ohio State
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health Sciences University
  • Pennsylvania
    • Easton, Pennsylvania, United States, 18045
      • Care Access Research
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University
    • Pittsburgh, Pennsylvania, United States, 15213
      • UPMC
  • South Carolina
    • Greenville, South Carolina, United States, 29607
      • Bon Secours Cancer Center
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57105
      • Avera Cancer
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Research Institute
  • Texas
    • Austin, Texas, United States, 78121
      • Texas Oncology P A
    • Dallas, Texas, United States, 75251
      • Texas Oncology
    • Fort Worth, Texas, United States, 76104
      • Ctr For Cancer And Blood Disorders
    • Houston, Texas, United States, 77030
      • Houston Methodist Hospital
    • Houston, Texas, United States, 77030
      • Univ of TX MD Anderson Cancer Cntr
    • San Antonio, Texas, United States, 78229
      • Mays Cancer Center
    • San Antonio, Texas, United States, 78258
      • Texas Oncology San Antonio
    • Tyler, Texas, United States, 75702
      • Texas Oncology Northeast Texas
  • Utah
    • Ogden, Utah, United States, 84405
      • Community Cancer Trials of Utah
    • Salt Lake City, Utah, United States, 84112
      • Huntsman Cancer Institute
  • Virginia
    • Gainesville, Virginia, United States, 20155
      • Virginia Cancer Specialists
    • Norfolk, Virginia, United States, 23502
      • Virginia Oncology Associates
    • Richmond, Virginia, United States, 23230
      • Virginia Cancer Institute
  • Washington
    • Seattle, Washington, United States, 98108
      • VA Puget Sound Health Care System
    • Seattle, Washington, United States, 98109
      • Fred Hutch Cancer Research
    • Tacoma, Washington, United States, 98405
      • Northwest Medical Specialties
  • Wisconsin
    • Madison, Wisconsin, United States, 53717
      • Dean Health System
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

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

Description

Key Inclusion Criteria:

Participants eligible for inclusion in this study must meet the following criteria: Criteria #1-5 are common to both patient cohorts (2L and 1L):

1. Signed informed consent must be obtained prior to participation in the study
2. CML-CP, no previous AP or BC
3. ≥ 18 years of age
4. ECOG performance status of 0, 1 or 2

5. Adequate end organ function within 14 days before the first dose of asciminib treatment.

   Patients with mild to moderate renal and hepatic impairment are eligible if:

   • Total bilirubin ≤ 3.0 x ULN without AST/ALT increase
   • Aspartate transaminase (AST) ≤ 5.0 x ULN
   • Alanine transaminase (ALT) ≤ 5.0 x ULN
   • Serum lipase ≤ 1.5 x ULN. For serum lipase > ULN and ≤ 1.5 x ULN, value should be considered not clinically significant and not associated with risk factors for acute pancreatitis
   • Alkaline phosphatase ≤ 2.5 x ULN
   • Creatinine clearance ≥ 30 mL/min as calculated using Cockcroft- Gault formula

   Criteria #6 and 7 are specific to the 2L patient cohort. These are meant to be either/or. It is not required to have both criteria satisfied.

6. Warning or failure (according to 2020 ELN Recommendations; Hochhaus et al) to 1L TKI therapy at the time of screening

   a. Warning is defined as: i. Six months after the initiation of treatment: BCR::ABL1IS >1-10% ii. Twelve months after the initiation of treatment: BCR::ABL1IS >0.1-1% b. Treatment failure/resistance to 1L TKI is defined as: i. BCR::ABL1IS >10% if 1L treatment duration between 6 and 12 months ii. BCR::ABL1IS >1% if 1L treatment longer than 12 months treatment iii. Beyond 12 months after initiation of treatment: loss of MMR

7. Treatment intolerance to 1L TKI,

   1. BCR::ABL1IS > 0.1% at screening
   2. Intolerance is defined as:

   i. Non-hematologic intolerance: Patients with grade 3 or 4 toxicity while on therapy, or with persistent grade 2 toxicity, unresponsive to optimal management, including dose adjustments (unless dose reduction is not considered in the best interest of the patient if response is already suboptimal) ii. Hematologic intolerance: Patients with grade 3 or 4 toxicity (absolute neutrophil count [ANC] or platelets) while on therapy that is recurrent after dose reduction to the lowest doses recommended by manufacturer

   Criteria #8 is specific to the 1L patient cohort

8. Patients with newly diagnosed CML-CP (treatment with a prior TKI (imatinib, or nilotinib, or dasatinib or bosutinib) for ≤ 4 weeks is allowed)

Key Exclusion Criteria:

1. Previous treatment

   1. With 2 or more ATP-binding site TKIs (for 2L patient cohort)
   2. More than 4 weeks with 1-ATP-binding site TKIs (for 1L patient cohort)
2. Previous treatment with asciminib
3. Known presence of the T315I mutation at any time prior to study entry
4. Known second chronic phase of CML after previous progression to AP/BC
5. Previous treatment with a hematopoietic stem-cell transplantation
6. Patient planning to undergo allogeneic hematopoietic stem cell transplantation

7. Cardiac or cardiac repolarization abnormality, including any 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)
   • QTcF at screening ≥450 msec (male patients), ≥450 msec (female patients)
   • 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
8. History of acute pancreatitis within 1 year of study entry or past medical history of chronic pancreatitis
9. Participation in a prior investigational study within 30 days prior to enrollment or within 5 half-lives of the investigational product, whichever is longer

10. Treatment with medications that meet one of the following criteria is not allowed and should be switched to an alternative at least one week prior to the start of treatment with study treatment:

    • Strong inducers of CYP3A for patients on the dose of 80 mg QD and 200mg QD
    • Strong inducers and inhibitors of CYP3A for patients on the dose of 200 mg BID
11. Pregnant or nursing (lactating) women
12. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception. Highly effective contraception for women should be maintained throughout the study and for at least 7 days after the last dose.
13. Sexually active males unwilling to use a condom during intercourse while taking study treatment and for 7 days after stopping study (only for patients treated with asciminib).
14. 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).
15. 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.
16. Known hypersensitivity to the study treatment.

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: Asciminib; 80 mg initial oral dose taken once a day with possible dose escalation	Drug: asciminib; Supplied in 40 mg and 100 mg tablets for oral use to be taken daily. Dose may be increased at 6 and 12 months based on molecular response with BCR-ABL1 Polymerase Chain Reaction testing.; Other Names: ABL001

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of participants who achieve Major Molecular Response (MMR) in the 2L setting	MMR is defined as BCR::ABL1IS ≤ 0.1%. A patient will be counted as having achieved MMR at 12 month if he/she meets the MMR criterion at 12 month.	Baseline up to 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of participants achieving Molecular Response 4.5 (MR4.5) at 24 and 36 months	Percentage of participants who achieve MR4.5 (defined as a ≥ 4.5 log reduction in BCR::ABL1 transcripts compared to the standardized baseline equivalent to ≤ 0.0032% BCR::ABL1/ABL % by international scale as measured by real time Polymerase Chain Reaction [PCR]) at the specified visits, i.e., if a patient achieves an MR4.5 but then loses it before or at the visit, he/she will be considered as non-responder for MR4.5 at that time point.	Baseline, 24 and 36 months
MMR Rate at visit (other than 12 month)	Percentage of participants who achieve MMR (defined as BCR::ABL1IS ≤ 0.1%) at the specified visit, i.e., if a patient achieves an MMR earlier but then loses it at the visit, he/she will be considered as non-responder for MMR at the specified visit	Baseline, 3, 6, 18, 24, 30 and 36 months
MR2 Rate at visit	Percentage of participants who achieve MR2 (defined as a ≥ 2 log reduction in BCR::ABL1 transcripts) at the specified visit, i.e., if a patient achieves an MR2 earlier but then loses it at the visit, he/she will be considered as non-responder for MR2 at the specified visit	Baseline, 3, 6, 12, 18, 24, 30 and 36 months
MR4 Rate at visit	Percentage of participants who achieve MR4 (defined as a ≥ 4 log reduction in BCR::ABL1 transcripts) at the specified visit, i.e if a patient achieves an MR4 earlier, but then loses it at the visit, he/she will be considered as non-responder for MR4 at the specified visit	Baseline, 3, 6, 12, 18, 24, 30 and 36 months
MR4.5 Rate at visit	Percentage of participants who achieve MR4.5 (defined as a ≥ 4.5 log reduction in BCR::ABL1 transcripts) at the specified visit, i.e if a patient achieves an MR4.5 earlier, but then loses it at the visit, he/she will be considered as non-responder for MR4.5 at the specified visit	Baseline, 3, 6, 12, 18 and 30 months
MMR Rate by visit	Percentage of participants who achieve MMR at or before the specified visit, i.e., if a patient achieves an MMR but then loses it before or at the visit, he/she will still be considered as achieving MMR by that time point.	Baseline up to 3, 6, 12, 18, 24, 30 and 36 months
MR2 Rate by visit	Percentage of participants who achieve MR2 (defined as a ≥ 2 log reduction in BCR::ABL1 transcripts) at or before the specified visit, i.e., if a patient achieves an MR2 but then loses it before or at the visit, he/she will still be considered as achieving MR2 by that time point.	Baseline up to 3, 6, 12, 18, 24, 30 and 36 months
MR4 Rate by visit	Percentage of participants who achieve MR4 (defined as a ≥ 4 log reduction in BCR::ABL1 transcripts) at or before the specified visit, i.e., if a patient achieves an MR4 but then loses it before or at the visit, he/she will still be considered as achieving MR4 by that time point.	Baseline up to 3, 6, 12, 18, 24, 30 and 36 months
MR4.5 Rate by visit	Percentage of participants who achieve MR4.5 (defined as a ≥ 4.5 log reduction in BCR::ABL1 transcripts) at or before the specified visit, i.e., if a patient achieves an MR4.5 but then loses it before or at the visit, he/she will still be considered as achieving MR4.5 by that time point.	Baseline up to 3, 6, 12, 18, 24, 30 and 36 months
Time to MMR	Time to MMR is defined and calculated as date of first documented MMR - start date of study treatment +1 day.	Baseline up to 36 months
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.	Baseline up to 36 months
Time to Treatment Failure (TTF)	Time to treatment failure (TTF) is defined as the time from date of randomization to an event of treatment failure.	Baseline up to 36 months
Progression Free Survival (PFS)	Time from the first dose of study treatment to the earliest occurrence of documented progression to Accelerated Phase (AP) or Blast Crisis (BC) or the date of death from any cause, before the end of the treatment phase.	Baseline up to 36 months
Overall Survival (OS)	Time from the first dose of study treatment to death due to any cause during the study.	Baseline up to 36 months.
Number of Adverse Events and Serious Adverse Events	Clinically significant findings for vitals, laboratory values and electrocardiogram (ECG) will be reported as adverse events and or serious adverse events as determined by the investigator.	Baseline up to 36 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
To investigate MR2, MR4, MR4.5 rate at visit	MR2, MR4 and MR4.5 at all scheduled data collection time points except for MR4.5 at 24 month	Baseline up to 24 months

Collaborators and Investigators

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

Publications and helpful links

General Publications

• Atallah EL, Mauro MJ, Sasaki K, Levy MY, Koller P, Yang D, Laine D, Sabo J, Gu E, Cortes JE. Dose-escalation of second-line and first-line asciminib in chronic myeloid leukemia in chronic phase: the ASC2ESCALATE Phase II trial. Future Oncol. 2024;20(38):3065-3075. doi: 10.1080/14796694.2024.2402680. Epub 2024 Oct 10.

Study record dates

Study Major Dates

• Study Start (Actual): November 11, 2022
• Primary Completion (Actual): August 13, 2025
• Study Completion (Estimated): October 17, 2027

Study Registration Dates

• First Submitted: May 17, 2022
• First Submitted That Met QC Criteria: May 17, 2022
• First Posted (Actual): May 20, 2022

Study Record Updates

• Last Update Posted (Estimated): October 14, 2025
• Last Update Submitted That Met QC Criteria: October 9, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Keywords: adult; CML; BCR-ABL; Asciminib; T315I mutation; TKI; Tyrosine Kinase Inhibitor; Chronic Phase; MMR; molecular response; ASC2ESCALATE
• 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; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Pathological Conditions, Signs and Symptoms; Hemic and Lymphatic Diseases; Leukemia, Myeloid, Chronic-Phase; Tyrosine Kinase Inhibitors; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; asciminib
• Other Study ID Numbers: CABL001AUS08

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