Study of Efficacy of CML-CP Patients Treated With ABL001 Versus Bosutinib, Previously Treated With 2 or More TKIs

NCT03106779 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: CABL001A23012016-002461-66
• Study Type: interventional
• Target: 233
• Locations: 25 countries
• Sites: 88

Brief Summary

The purpose of this pivotal study was to compare the efficacy of asciminib (ABL001) with that of bosutinib in the treatment of patients with CML-CP having previously been treated with a minimum of two prior ATP-binding site TKIs. Patients intolerant to the most recent TKI therapy must have had BCR-ABL1 ratio \> 0.1% IS at screening and patients failing their most recent TKI therapy must have met the definition of treatment failure as per the 2013 European LeukemiaNet (ELN) recommendations. Patients with documented treatment failure as per 2013 ELN recommendations while on bosutinib treatment had the option to switch to asciminib treatment within 96 weeks after the last patient has been randomized on study.

Conditions

Chronic Myelogenous Leukemia

Keywords

Phase 3; Chronic Myelogenous Leukemia; CML; bosutinib; ABL001; tyrosine kinase inhibitor; 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

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Major Molecular Response (MMR) Rate at 24 Weeks

  MMR was defined as a ≥ 3.0 log reduction in BCR-ABL1 transcripts compared to the standardized baseline equivalent to ≤ 0.1% BCR-ABL1/ABL% by IS as measured by RQ-PCR.

  24 weeks

Secondary Outcomes (14)

• Number of Participants With Major Molecular Response (MMR) Rate

  96 weeks after the last patient received the first study dose

• Complete Cytogenetic Response Rate

  96 weeks after the last patient received the first study dose

• Time to MMR

  96 weeks after the last patient received the first study dose

• Duration of MMR

  96 weeks after the last patient received the first study dose

• Time to CCyR

  96 weeks after the last patient received the first study dose

Study Arms (2)

Asciminib

EXPERIMENTAL

Patients were randomized to asciminib 40mg BID

Drug: Asciminib

Bosutinib

ACTIVE COMPARATOR

Patients were randomized to bosutinib 500mg QD

Drug: Bosutinib

Interventions

Asciminib DRUG

40 mg tablets was taken orally twice a day (BID)

Also known as: ABL001

Asciminib

Bosutinib DRUG

500 mg tablets was taken orally once daily (QD)

Bosutinib

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patients with a diagnosis of CML-CP ≥ 18 years of age
• Patients must meet all of the following laboratory values at the screening visit:
• \< 15% blasts in peripheral blood and bone marrow
• \< 30% blasts plus promyelocytes in peripheral blood and bone marrow
• \< 20% basophils in the peripheral blood
• ≥ 50 x 109/L (≥ 50,000/mm3) platelets
• Transient prior therapy related thrombocytopenia (\< 50,000/mm3 for ≤ 30 days prior to screening) is acceptable
• No evidence of extramedullary leukemic involvement, with the exception of hepatosplenomegaly
• BCR-ABL1 ratio \> 0.1% IS according to central laboratory at the screening examination for patients intolerant to the most recent TKI therapy
• Prior treatment with a minimum of 2 prior ATP-binding site TKIs (i.e. imatinib, nilotinib, dasatinib, radotinib or ponatinib)
• Failure (adapted from the 2013 ELN Guidelines Bacarrani 2013) or intolerance to the most recent TKI therapy at the time of screening
• Failure is defined for CML-CP patients (CP at the time of initiation of last therapy) as follows. Patients must meet at least 1 of the following criteria.
• Three months after the initiation of therapy: No CHR or \> 95% Ph+ metaphases
• Six months after the initiation of therapy: BCR-ABL1 ratio \> 10% IS and/or \> 65% Ph+ metaphases
• Twelve months after initiation of therapy: BCR-ABL1 ratio \> 10% IS and/or \> 35% Ph+ metaphases

You may not qualify if:

• Known presence of the T315I or V299L 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
• 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), ≥460 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
• 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, pulmonary hypertension)
• History of acute pancreatitis within 1 year of study entry or past medical history of chronic pancreatitis
• History of acute or chronic liver disease
• Treatment with medications that meet one of the following criteria and that cannot be discontinued at least one week prior to the start of treatment with study treatment
• Moderate or strong inducers of CYP3A
• Moderate or strong inhibitors of CYP3A

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (88)

University of Chicago Hospital

Chicago, Illinois, 60637, United States

Location

Indiana Blood and Marrow Institute

Beech Grove, Indiana, 46107, United States

Location

Sidney Kimmel Comprehensive Cancer Center

Baltimore, Maryland, 21205, United States

Location

Dana Farber Cancer Center

Boston, Massachusetts, 02215, United States

Location

University of Michigan Clinical Trials Office

Ann Arbor, Michigan, 48109, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

Weill Cornell Medicine NY-Presb

New York, New York, 10021, United States

Location

Memorial Sloan Kettering Cancer Ctr

New York, New York, 10065, United States

Location

Uni Of TX MD Anderson Cancer Cntr

Houston, Texas, 77030, United States

Location

Utah Huntsman Cancer Center

Salt Lake City, Utah, 84112, United States

Location

Novartis Investigative Site

CABA, Buenos Aires, C1221ADH, Argentina

Location

Novartis Investigative Site

Capital Federal, C1114AAN, Argentina

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Novartis Investigative Site

Córdoba, X5016KEH, Argentina

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Novartis Investigative Site

Adelaide, South Australia, 5000, Australia

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Novartis Investigative Site

Melbourne, Victoria, 3000, Australia

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Novartis Investigative Site

Murdoch, Western Australia, 6150, Australia

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Novartis Investigative Site

Rio de Janeiro, Rio de Janeiro, 20211-030, Brazil

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Novartis Investigative Site

São Paulo, São Paulo, 05403 000, Brazil

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Novartis Investigative Site

São Paulo, São Paulo, 08270-070, Brazil

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Novartis Investigative Site

Porto Alegre, 90035-003, Brazil

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Novartis Investigative Site

Plovdiv, 4002, Bulgaria

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Novartis Investigative Site

Varna, 9000, Bulgaria

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Novartis Investigative Site

Toronto, Ontario, M5G 2M9, Canada

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Novartis Investigative Site

Ostrava, Poruba, 708 52, Czechia

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Novartis Investigative Site

Brno-Bohunice, 625 00, Czechia

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Novartis Investigative Site

Bordeaux, 33076, France

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Novartis Investigative Site

Lyon, 69373, France

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Novartis Investigative Site

Marseille, 13273, France

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Novartis Investigative Site

Paris, 75475, France

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Novartis Investigative Site

Vandœuvre-lès-Nancy, 54511, France

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Novartis Investigative Site

Mannheim, Baden-Wurttemberg, 68305, Germany

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Novartis Investigative Site

Frankfurt am Main, Hesse, 60590, Germany

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Novartis Investigative Site

Berlin, 13353, Germany

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Novartis Investigative Site

Düsseldorf, 40225, Germany

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Novartis Investigative Site

Heidelberg, 69120, Germany

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Novartis Investigative Site

Jena, 07740, Germany

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Novartis Investigative Site

Kiel, 24116, Germany

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Novartis Investigative Site

Budapest, H-1097, Hungary

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Novartis Investigative Site

Debrecen, 4032, Hungary

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Novartis Investigative Site

Jerusalem, 9112001, Israel

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Novartis Investigative Site

Ẕerifin, 7030000, Israel

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Novartis Investigative Site

Bari, BA, 70124, Italy

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Novartis Investigative Site

Milan, MI, 20122, Italy

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Novartis Investigative Site

Napoli, 80132, Italy

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Novartis Investigative Site

Nagoya, Aichi-ken, 453-8511, Japan

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Novartis Investigative Site

Toyoake, Aichi-ken, 470 1192, Japan

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Novartis Investigative Site

Kashiwa, Chiba, 277 8577, Japan

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Novartis Investigative Site

Ōsaka-sayama, Osaka, 589 8511, Japan

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Novartis Investigative Site

Suita, Osaka, 565 0871, Japan

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Novartis Investigative Site

Bunkyo Ku, Tokyo, 113-8677, Japan

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Novartis Investigative Site

Chūō, Yamanashi, 409-3898, Japan

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Novartis Investigative Site

Akita, 010-8543, Japan

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Novartis Investigative Site

Aomori, 030 8553, Japan

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Novartis Investigative Site

Kobe, 650-0017, Japan

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Novartis Investigative Site

Beirut, 1107 2020, Lebanon

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Novartis Investigative Site

El Achrafiyé, 166830, Lebanon

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Novartis Investigative Site

Monterrey, Nuevo León, 64460, Mexico

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Novartis Investigative Site

Amsterdam, 1081 HV, Netherlands

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Novartis Investigative Site

Dordrecht, 3318 AT, Netherlands

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Novartis Investigative Site

Cluj-Napoca, 400124, Romania

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Novartis Investigative Site

Timișoara, 300079, Romania

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Novartis Investigative Site

Moscow, 125167, Russia

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Novartis Investigative Site

Moscow, 125284, Russia

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Novartis Investigative Site

Saint Petersburg, 191024, Russia

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Novartis Investigative Site

Saint Petersburg, 197341, Russia

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Novartis Investigative Site

Riyadh, 11211, Saudi Arabia

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Novartis Investigative Site

Belgrade, 11000, Serbia

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Novartis Investigative Site

Novi Sad, 400107, Serbia

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Novartis Investigative Site

Uijeongbu-si, Gyeonggi-do, 11759, South Korea

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Novartis Investigative Site

Seoul, Seocho Gu, 06591, South Korea

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Novartis Investigative Site

Busan, 49201, South Korea

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Novartis Investigative Site

Jeollanam, 519763, South Korea

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Novartis Investigative Site

Bilbao, Basque Country, 48013, Spain

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Novartis Investigative Site

Toledo, Castille-La Mancha, 45071, Spain

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Novartis Investigative Site

Barcelona, Catalonia, 08036, Spain

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Novartis Investigative Site

L'Hospitalet de Llobregat, Catalonia, 08907, Spain

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Novartis Investigative Site

Madrid, 28034, Spain

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Novartis Investigative Site

Zurich, 8091, Switzerland

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Novartis Investigative Site

Istanbul, TUR, 34098, Turkey (Türkiye)

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Novartis Investigative Site

Adana, 01330, Turkey (Türkiye)

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Novartis Investigative Site

Istanbul, 34093, Turkey (Türkiye)

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Novartis Investigative Site

Izmir, 35100, Turkey (Türkiye)

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Novartis Investigative Site

Samsun, 55139, Turkey (Türkiye)

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Novartis Investigative Site

Cardiff, CF14 4XW, United Kingdom

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Novartis Investigative Site

Glasgow, G12 0YN, United Kingdom

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Novartis Investigative Site

Liverpool, CH63 4JY, United Kingdom

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Novartis Investigative Site

London, W12 0HS, United Kingdom

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Novartis Investigative Site

Oxford, OX3 7LE, United Kingdom

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Related Publications (5)

• Mauro MJ, Minami Y, Hochhaus A, Lomaia E, Voloshin S, Turkina A, Kim DW, Apperley JF, Cortes JE, Abdo A, Fogliatto LM, Kim DDH, le Coutre P, Saussele S, Annunziata M, Hughes TP, Chaudhri N, Chee L, Garcia-Gutierrez V, Sasaki K, Boquimpani C, Kapoor S, Espurz N, Dhamal V, Rea D. Asciminib remained superior vs bosutinib in late-line CML-CP after nearly 4 years of follow-up in ASCEMBL. Blood Adv. 2025 Aug 26;9(16):4248-4259. doi: 10.1182/bloodadvances.2025016042.

  PMID: 40334072 DERIVED

• Cortes JE, Rea D, Mauro MJ, Tran D, Wang P, Jadhav K, Yocolly A, Sasaki K. Health care resource utilization in 3L + patients with chronic phase chronic myeloid leukemia receiving asciminib or bosutinib. J Med Econ. 2023 Jan-Dec;26(1):915-923. doi: 10.1080/13696998.2023.2234776.

  PMID: 37431294 DERIVED

• Yuda J, Doki N, Matsuoka H, Yokota T, Tomita A, Takahashi N, Matsumura I, Kubo K, Goto T, Kirito K, Maki A, Aoki M, Allepuz A, Minami Y. Asciminib vs bosutinib in CML patients pretreated with >/=2 tyrosine kinase inhibitors: Results from the Japanese subgroup analysis of ASCEMBL study. Cancer Med. 2023 Feb;12(3):2990-2998. doi: 10.1002/cam4.5212. Epub 2022 Sep 27.

  PMID: 36168187 DERIVED

• Li YF, Combes FP, Hoch M, Lorenzo S, Sy SKB, Ho YY. Population Pharmacokinetics of Asciminib in Tyrosine Kinase Inhibitor-Treated Patients with Philadelphia Chromosome-Positive Chronic Myeloid Leukemia in Chronic and Acute Phases. Clin Pharmacokinet. 2022 Oct;61(10):1393-1403. doi: 10.1007/s40262-022-01148-9. Epub 2022 Jun 28.

  PMID: 35764773 DERIVED

• Rea D, Mauro MJ, Boquimpani C, Minami Y, Lomaia E, Voloshin S, Turkina A, Kim DW, Apperley JF, Abdo A, Fogliatto LM, Kim DDH, le Coutre P, Saussele S, Annunziata M, Hughes TP, Chaudhri N, Sasaki K, Chee L, Garcia-Gutierrez V, Cortes JE, Aimone P, Allepuz A, Quenet S, Bedoucha V, Hochhaus A. A phase 3, open-label, randomized study of asciminib, a STAMP inhibitor, vs bosutinib in CML after 2 or more prior TKIs. Blood. 2021 Nov 25;138(21):2031-2041. doi: 10.1182/blood.2020009984.

  PMID: 34407542 DERIVED

MeSH Terms

Conditions

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Interventions

asciminib; bosutinib

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Limitations and Caveats

In the asciminib arm, 2 patients died on-treatment and 2 patients died during survival follow-up. In the bosutinib arm, 1 patient died on-treatment.

Results Point of Contact

• Title: Clinical Disclosure Office
• Organization: Novartis Pharmaceuticals

novartis.email@novartis.com

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 9, 2017
• First Posted: April 10, 2017
• Study Start: October 26, 2017
• Primary Completion: May 25, 2020
• Study Completion: December 4, 2024
• Last Updated: April 8, 2025
• Results First Posted: February 15, 2022

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will share

Locations

SE (2); IL (2); BU (2); AR (3); ME (1); AU (3); BR (4); HU (2); DE (7); NL (2); SA (1); KR (4); RO (2); ES (5); FR (5); CA (1); US (10); IT (3); CH (1); TU (5); LE (2); JP (10); GB (5); RU (4); CZ (2)