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

NCT04971226 | Active Not Recruiting Phase 3 Results DMC FDA Drug

• 2 other identifiers: CABL001J123012023-508838-33-00
• Study Type: interventional
• Target: 406
• Locations: 28 countries
• Sites: 109

Brief Summary

The study is designed to compare the efficacy of asciminib 80 mg QD versus Investigator selected Tyrosine Kinase Inhibitor (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. This study has three periods: 1. Treatment period for all randomized participants, 2. Optional Treatment-Free Remission (TFR) period only for participants meeting TFR eligibility criteria and 3. Treatment Re-Initiation (TRI) period only for participants who relapsed after TFR attempt.

Conditions

Chronic Myeloid Leukemia (CML) Philadelphia Chromosome Positive

Keywords

Asciminib; Chronic Myeloid Leukemia; CML; Philadelphia Chromosome; TKIs; Bosutinib; Dasatinib; Nilotinib; Imatinib; Treatment-free remission

Outcome Measures

Primary Outcomes (2)

• Percentage of Participants With Major Molecular Response (MMR) at Week 48 - Ascimimib vs. Investigator Selected TKI

  Molecular response is assessed using BCR-ABL1 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

• Percentage of Participants With Major Molecular Response (MMR) at Week 48 - Asciminib (Imatinib Stratum) vs Investigator Selected TKI (Imatinib Stratum)

  Molecular response is assessed using BCR-ABL1 transcript levels measured by realtime quantitative polymerase chain reaction. MMR is defined as a ratio BCR-ABL1/ABL ≤0.1% on the international scale (ie, at least 3 log reduction from a standardized baseline value).

  At 48 weeks

Secondary Outcomes (31)

• Major Molecular Response at Week 96

  at 96 weeks (96 weeks after last patient first dose)

• Time to Discontinuation of Study Treatment Due to Adverse Events (TTDAE)

  96 weeks after last patient first dose

• Major Molecular Response at Scheduled Data Collection Time Points

  Planned total follow-up duration of 5 years

• Major Molecular Response by Scheduled Data Collection Time Points

  Planned total follow-up duration of 5 years

• MR4.0 at Scheduled Data Collection Time Points

  Planned total follow-up duration of 5 years

Study Arms (2)

Asciminib

EXPERIMENTAL

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

Investigator selected TKIs

ACTIVE COMPARATOR

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; Drug: Nilotinib; Drug: Bosutinib; Drug: Dasatinib

Interventions

Imatinib DRUG

Comes in 100 mg and 400 mg tablets and taken orally

Also known as: STI571

Investigator selected TKIs

Nilotinib DRUG

Comes in 150 mg and 200 mg capsules and taken orally

Also known as: AMN107

Investigator selected TKIs

Bosutinib DRUG

Comes in 100 mg and 400 mg tablets and taken orally

Investigator selected TKIs

Dasatinib DRUG

Comes in 20 mg, 50 mg, 70 mg and 100 mg tablets and taken orally

Investigator selected TKIs

Asciminib DRUG

Comes in 40 mg tablets and taken orally

Also known as: ABL001

Asciminib

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 ≥ 18 years of age.
• Participants with CML-CP within 3 months of diagnosis.
• 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 10\^9/L (≥ 100,000/mm\^3),
• No evidence of extramedullary leukemic involvement, with the exception of hepatosplenomegaly.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• 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
• \- Participants must have the following laboratory values within normal limits or corrected to within normal limits with supplements prior to randomization:

You may not qualify if:

• 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.
• Known cytopathologically confirmed CNS infiltration (in absence of suspicion of CNS involvement, lumbar puncture not required).
• 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
• 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
• History of significant congenital or acquired bleeding disorder unrelated to cancer.
• Major surgery within 4 weeks prior to study entry or who have not recovered from prior surgery.
• 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
• History of acute pancreatitis within 1 year prior to randomization or medical history of chronic pancreatitis.
• History of chronic liver disease leading to severe hepatic impairment, or ongoing acute liver disease.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (110)

Rocky Mountain Cancer Centers

Denver, Colorado, 80218, United States

Location

Florida Cancer Specialists

Fort Myers, Florida, 33901, United States

Location

Florida Cancer Specialists Pan

Tallahassee, Florida, 32308, United States

Location

University of Kentucky

Lexington, Kentucky, 40536, United States

Location

Uni of Massachusetts Medical Center

Worcester, Massachusetts, 01655, United States

Location

Wake Forest University Baptist Medical Center

Winston-Salem, North Carolina, 27157, United States

Location

Williamette Cancer Center

Eugene, Oregon, 97401, United States

Location

Oregon Health Sciences University

Portland, Oregon, 97239, United States

Location

Avera Cancer

Sioux Falls, South Dakota, 57105, United States

Location

Chattanooga Onc And Hem Assoc PC

Chattanooga, Tennessee, 37404, United States

Location

Texas Oncology-Baylor USO

Dallas, Texas, 75246, United States

Location

Texas Oncology

Dallas, Texas, 75246, United States

Location

Texas Oncology

Dallas, Texas, 75251, United States

Location

Novartis Investigative Site

Kingswood, New South Wales, 2747, Australia

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Novartis Investigative Site

Port Macquarie, New South Wales, 2444, Australia

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Novartis Investigative Site

Adelaide, South Australia, 5000, Australia

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Novartis Investigative Site

Southport, 4215, Australia

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Novartis Investigative Site

Linz, Upper Austria, 4010, Austria

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Novartis Investigative Site

Leuven, Vlaams Brabant, 3000, Belgium

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Novartis Investigative Site

Brussels, 1000, Belgium

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Novartis Investigative Site

Varna, 9010, Bulgaria

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Calgary, Alberta, T2N 5G2, Canada

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Novartis Investigative Site

Hamilton, Ontario, L8V 1C3, Canada

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Novartis Investigative Site

Ottawa, Ontario, K1H 8L6, Canada

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Novartis Investigative Site

Toronto, Ontario, M5G 2M9, Canada

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Novartis Investigative Site

Guangzhou, Guangdong, 510515, China

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Novartis Investigative Site

Shenzhen, Guangdong, 518037, China

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Novartis Investigative Site

Zhengzhou, Henan, 450008, China

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Wuhan, Hubei, 430022, China

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Nanjing, Jiangsu, 210000, China

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Novartis Investigative Site

Suzhou, Jiangsu, 215004, China

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Xian, Shanxi, 710068, China

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Chengdu, Sichuan, 610041, China

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Hangzhou, Zhejiang, 310003, China

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Wenzhou, Zhejiang, 325000, China

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Beijing, 100044, China

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Novartis Investigative Site

Beijing, 100730, China

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Novartis Investigative Site

Lanzhou, 730000, China

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Novartis Investigative Site

Tianjin, 300020, China

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Novartis Investigative Site

Ostrava, Poruba, 708 52, Czechia

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Novartis Investigative Site

Brno, 625 00, Czechia

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Novartis Investigative Site

Hradec Králové, 500 05, Czechia

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Aarhus N, 8200, Denmark

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Copenhagen, DK-2100, Denmark

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Helsinki, FIN 00290, Finland

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Bordeaux, 33076, France

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Lyon, 69373, France

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Nantes, 44093, France

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Paris, 75475, France

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Mannheim, Baden-Wurttemberg, 68305, Germany

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Frankfurt am Main, Hesse, 60590, Germany

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Jena, Thuringia, 07740, Germany

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Aachen, 52074, Germany

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Berlin, 13353, Germany

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Lübeck, 23538, Germany

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Debrecen, Hajdu Bihar Megye, 4032, Hungary

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Kaposvár, 7400, Hungary

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Kecskemét, 6001, Hungary

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Delhi, 110085, India

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Petah Tikva, 4941492, Israel

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Ramat Gan, 5265601, Israel

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Tel Aviv, 6423906, Israel

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Bologna, BO, 40138, Italy

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Milan, MI, 20122, Italy

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Reggio Emilia, RE, 42123, Italy

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Roma, RM, 00161, Italy

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Verona, VR, 37134, Italy

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Nagoya, Aichi-ken, 453-8511, Japan

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Toyoake, Aichi-ken, 4701192, Japan

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Sapporo, Hokkaido, 0608648, Japan

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Kobe, Hyōgo, 6500047, Japan

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Kurashiki, Okayama-ken, 7108602, Japan

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Sakai, Osaka, 590-0197, Japan

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Novartis Investigative Site

Suita, Osaka, 5650871, Japan

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Novartis Investigative Site

Shimotsuke, Tochigi, 329-0498, 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

Fukuoka, 8128582, Japan

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Fukushima, 9601295, Japan

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Novartis Investigative Site

Osaka, 5458586, Japan

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Novartis Investigative Site

Yamagata, 990 9585, Japan

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Kuantan, Pahang, 25100, Malaysia

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George Town, Pulau Pinang, 10450, Malaysia

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Subang Jaya, Selangor, 47500, Malaysia

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Kuala Selangor, 68000, Malaysia

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Amsterdam, North Holland, 1081 HV, Netherlands

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Bergen, NO-5021, Norway

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Oslo, 0372, Norway

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Porto, 4200-072, Portugal

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Novartis Investigative Site

Vila Nova de Gaia, 4434 502, Portugal

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Singapore, 119074, Singapore

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Singapore, 169608, Singapore

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Košice, 041 90, Slovakia

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

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Seoul, Korea, 03080, South Korea

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Novartis Investigative Site

Seoul, 06351, South Korea

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Novartis Investigative Site

Seoul, 06591, South Korea

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Granada, Andalusia, 18014, Spain

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El Palmar, Murcia, 30120, Spain

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Pamplona, Navarre, 31008, Spain

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Barcelona, 08036, Spain

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Madrid, 28046, Spain

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Gothenburg, 413 45, Sweden

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Lund, 221 85, Sweden

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Stockholm, 141 86, Sweden

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Bellinzona, 6850, Switzerland

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Taichung, 40447, Taiwan

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London, W12 0HS, United Kingdom

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Nottingham, NG5 1PB, United Kingdom

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Oxford, OX3 7LE, United Kingdom

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Related Publications (3)

• Cortes JE, Hughes TP, Wang J, Kim DW, Kim DDH, Mayer J, Goh YT, le Coutre P, Etienne G, Kim I, Andorsky DJ, Bombaci F, Issa GC, Takahashi N, Kapoor S, Jinwal R, Malek K, McCulloch T, Yau L, Larson RA, Hochhaus A. Asciminib demonstrates superior efficacy and safety in newly diagnosed chronic myeloid leukemia in the ASC4FIRST trial. Blood. 2026 Mar 26;147(13):1433-1446. doi: 10.1182/blood.2025029210.

  PMID: 41397287 DERIVED

• Hochhaus A, Wang J, Kim DW, Kim DDH, Mayer J, Goh YT, le Coutre P, Takahashi N, Kim I, Etienne G, Andorsky D, Issa GC, Larson RA, Bombaci F, Kapoor S, McCulloch T, Malek K, Yau L, Ifrah S, Hoch M, Cortes JE, Hughes TP; ASC4FIRST Investigators. Asciminib in Newly Diagnosed Chronic Myeloid Leukemia. N Engl J Med. 2024 Sep 12;391(10):885-898. doi: 10.1056/NEJMoa2400858. Epub 2024 May 31.

  PMID: 38820078 DERIVED

• Cortes JE, Hochhaus A, Takahashi N, Larson RA, Issa GC, Bombaci F, Ramscar N, Ifrah S, Hughes TP. Asciminib monotherapy for newly diagnosed chronic myeloid leukemia in chronic phase: the ASC4FIRST phase III trial. Future Oncol. 2022 Dec;18(38):4161-4170. doi: 10.2217/fon-2022-0923. Epub 2022 Dec 16.

  PMID: 36524980 DERIVED

MeSH Terms

Conditions

Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Philadelphia Chromosome

Interventions

Imatinib Mesylate; nilotinib; bosutinib; Dasatinib; asciminib

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; Translocation, Genetic; Chromosome Aberrations

Intervention Hierarchy (Ancestors)

Benzamides; Amides; Organic Chemicals; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines; Thiazoles; Sulfur Compounds; Azoles

Limitations and Caveats

Adverse Events data were not collected from the 4 participants who are not included in the Safety Set as they did not receive any treatment.

Results Point of Contact

• Title: Clinical Disclosure Office
• Organization: Novartis Pharmaceuticals

novartis.email@novartis.com

862-778-3000

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
• Expanded Access: Yes

Study Record Dates

• First Submitted: June 8, 2021
• First Posted: July 21, 2021
• Study Start: October 6, 2021
• Primary Completion: November 28, 2023
• Study Completion (Estimated): January 18, 2031
• Last Updated: March 10, 2026
• Results First Posted: March 10, 2025

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share

Locations

NO (2); TW (1); PT (2); FI (1); US (13); KR (4); DK (2); CN (14); IN (1); BU (1); AU (4); HU (3); SL (1); JP (14); NL (1); CZ (3); CA (4); ES (5); DE (6); SE (3); BE (2); SG (2); CH (1); FR (4); IT (5); IL (3); MY (4); GB (3)