Asciminib for Chronic Myeloid Leukemia

Overseen By Ghayas Issa, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must be taking: TKI therapy

Must not be taking: QT prolonging drugs

Disqualifiers: T315I mutation, Heart failure, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 28

Duration: 24 months

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a drug called asciminib for individuals with chronic myeloid leukemia (CML), a type of blood cancer, who have not responded adequately to one previous treatment. The goal is to determine if asciminib can better control the disease. It targets those with a specific genetic marker (BCR-ABL positive) who have experienced treatment failure, such as insufficient improvement after initial therapies. Participants should manage daily activities without significant difficulty and maintain stable health conditions overall. As a Phase 2 trial, this research measures how well asciminib works in an initial, smaller group, offering a chance to potentially benefit from a promising treatment.

Will I have to stop taking my current medications?

Participants must stop taking imatinib, bosutinib, dasatinib, nilotinib, or other anti-leukemia therapies (except hydroxyurea) at least 48 hours before starting the study treatment. The use of hydroxyurea is allowed immediately before joining the study.

Is there any evidence suggesting that asciminib is likely to be safe for humans?

Research has shown that asciminib is generally well-tolerated by patients with chronic myeloid leukemia (CML). Studies have found that asciminib often causes fewer and less severe side effects compared to other treatments. However, thrombocytopenia, or a reduced platelet count, is the most common side effect, which can increase the risk of bleeding or bruising. Overall, asciminib has a favorable safety profile, making it a promising option for those seeking a treatment with fewer side effects. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Asciminib is unique because it targets the BCR-ABL1 protein in a different way than current treatments for chronic myeloid leukemia (CML). Most treatments, like imatinib or dasatinib, inhibit the ATP-binding site of BCR-ABL1, while asciminib specifically targets the myristoyl pocket, offering a novel mechanism of action. Researchers are excited about asciminib because it has the potential to be effective for patients who have developed resistance to other therapies, providing a new hope for those who have limited options.

What evidence suggests that asciminib might be an effective treatment for chronic myeloid leukemia?

Studies have shown that asciminib effectively treats chronic myeloid leukemia (CML). For newly diagnosed CML patients, asciminib proved more effective than treatments like tyrosine kinase inhibitors (TKIs). Research also indicates that asciminib is safe and effective for long-term use, even for those who have tried other treatments. Specifically, a study in Italy found positive results for patients in the early stage of CML using asciminib. Overall, the evidence supports asciminib as a promising option for managing CML. ^{2 4 6 7 8}

Who Is on the Research Team?

Ghayas Issa, MD

Principal Investigator

The University of Texas MD Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for individuals with Chronic Myeloid Leukemia in the chronic phase who have already tried at least one treatment. Participants should have a specific mutation in their cancer cells (CKIT or PDGFRA).

Inclusion Criteria

My liver and kidney functions meet the required levels for treatment.

I have chronic phase CML with a positive Ph or BCR-ABL and have had one prior TKI treatment.

I can take care of myself but might not be able to do heavy physical work.

Exclusion Criteria

ANC < 500/mm3, platelet count < 50,000 mm3

Corrected QT interval (QTc) of > 450 milliseconds (ms) on baseline electrocardiogram (ECG or EKG) (using the Fridericia Formula)

Subject has any other significant medical or psychiatric history that in the opinion of the investigator would adversely affect participation in this study

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive asciminib 80 mg once daily continuously for 28-day cycles for 2 years

24 months

Monthly visits for 28-day cycles

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

What Are the Treatments Tested in This Trial?

Interventions

• Asciminib

Trial Overview

The study is testing Asciminib's effectiveness and safety as a second-line treatment for Chronic Myeloid Leukemia. It aims to see how well patients respond to this medication after other treatments.

How Is the Trial Designed?

Group I: Asciminib Experimental Treatment 1 Intervention

Patients will receive asciminib 80 mg once daily continuously for 28-day cycles for 2 years.

Asciminib is already approved in United States, European Union for the following indications:

Approved in United States as Scemblix for:

• Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) in chronic phase (CP) in adults previously treated with ≥2 tyrosine kinase inhibitors (TKIs)
• Ph+ CML in CP with the T315I mutation
• newly diagnosed Ph+ CML in CP

Approved in European Union as Scemblix for:

• Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) in chronic phase (CP) in adults previously treated with ≥2 tyrosine kinase inhibitors (TKIs)
• Ph+ CML in CP with the T315I mutation

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Novartis

Industry Sponsor

Trials

1,646

Recruited

2,778,000+

Vasant Narasimhan

Novartis

Chief Executive Officer since 2018

MD from Harvard Medical School, Bachelor's in Biological Sciences from University of Chicago, Master's in Public Policy from John F. Kennedy School of Government

Shreeram Aradhye

Novartis

Chief Medical Officer since 2022

MD from Yale University, MSc in Clinical Epidemiology from University of Pennsylvania

Published Research Related to This Trial

Asciminib hydrochloride, the first tyrosine kinase inhibitor targeting the ABL myristoyl pocket, was approved for chronic myeloid leukemia (CML) patients who are resistant or intolerant to prior therapies, showing significant antitumor effects in both lab and animal studies.

In a phase III study, asciminib demonstrated superior efficacy compared to bosutinib in achieving a major molecular response at week 24 for patients with chronic phase CML previously treated with multiple TKIs, with the most common side effect being thrombocytopenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Pharmacological and clinical profile of asciminib hydrochloride, a novel first-in-class tyrosine kinase inhibitor specifically targeting ABL myristoyl pocket]. Chung, J., Ariyoshi, T., Yoneda, T., et al.[2023]

Asciminib is the first drug that specifically targets the ABL myristoyl pocket, showing promising efficacy and safety in patients with chronic myeloid leukemia (CML) who have previously been treated with multiple tyrosine kinase inhibitors (TKIs).

The ongoing phase III trial (ASC4FIRST) is comparing asciminib to standard TKIs in newly diagnosed CML patients, with the primary goal of achieving a major molecular response by week 48, highlighting its potential as a new treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Asciminib monotherapy for newly diagnosed chronic myeloid leukemia in chronic phase: the ASC4FIRST phase III trial. Cortes, JE., Hochhaus, A., Takahashi, N., et al.[2023]

Asciminib, a new treatment for chronic myeloid leukemia (CML), showed superior efficacy compared to bosutinib, with a major molecular response rate of 37.6% versus 15.8% after 96 weeks in patients who had previously been treated with two or more tyrosine kinase inhibitors.

Patients taking asciminib experienced fewer severe adverse events and were more likely to continue treatment without discontinuation, indicating better safety and tolerability compared to bosutinib.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Asciminib vs bosutinib in chronic-phase chronic myeloid leukemia previously treated with at least two tyrosine kinase inhibitors: longer-term follow-up of ASCEMBL. Hochhaus, A., Réa, D., Boquimpani, C., et al.[2023]

Asciminib (Scemblix®) is an innovative oral medication that selectively inhibits the BCR-ABL1 tyrosine kinase, specifically targeting the myristoyl pocket, making it effective against certain mutations like T315I that resist traditional treatments.

In October 2021, asciminib received accelerated approval for adults with Philadelphia chromosome-positive chronic myeloid leukaemia (CML) who have previously been treated with at least two other tyrosine kinase inhibitors, highlighting its efficacy in difficult-to-treat cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Asciminib: First Approval. Deeks, ED.[2022]

In a phase 3 study, asciminib showed significant superiority over bosutinib in achieving major molecular response (MMR) in Japanese patients with chronic myeloid leukemia (CML) who had previously been treated with at least two tyrosine kinase inhibitors, with an MMR rate of 30.8% at week 24.

The safety profile of asciminib was comparable to that observed in the overall study population, supporting its use as an effective treatment option for Japanese patients with CML-CP.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Asciminib vs bosutinib in CML patients pretreated with ≥2 tyrosine kinase inhibitors: Results from the Japanese subgroup analysis of ASCEMBL study. Yuda, J., Doki, N., Matsuoka, H., et al.[2023]

Asciminib is a first-in-class BCR::ABL1 inhibitor that specifically targets the ABL myristoyl pocket, showing promise in overcoming resistance or intolerance to existing tyrosine kinase inhibitors (TKIs) in chronic myeloid leukemia (CML) patients.

Clinical data indicate that asciminib has considerable efficacy in CML patients who have failed at least two prior TKIs, with a favorable safety profile and low cross-intolerance with other TKIs, making it a significant advancement in CML treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An evaluation of asciminib for patients with chronic myeloid leukemia previously treated with ≥2 tyrosine kinase inhibitors. García-Gutiérrez, V., Hernandez-Boluda, JC.[2022]

Citations

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pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC12064212/

Real‐World Efficacy Profile of Compassionate Use ...

This retrospective Italian analysis reports the efficacy and safety outcomes of asciminib in treating 77 CML patients in chronic phase (CML‐CP) ...

2.

nature.com

nature.com/articles/s41375-025-02578-7

Asciminib monotherapy in patients with chronic myeloid ...

With up to 8.4 years of treatment, asciminib continued to demonstrate long-term safety and efficacy in this population.

3.

novartis.com

novartis.com/news/media-releases/longer-term-data-novartis-scemblix-reinforce-superior-efficacy-favorable-safety-and-tolerability-profile-adults-newly-diagnosed-cml

Longer-term data for Novartis Scemblix® reinforce superior ...

Asciminib Continues to Provide Superior Efficacy and Favorable Safety and Tolerability vs Tyrosine Kinase Inhibitors In Newly Diagnosed Chronic ...

4.

clinicaltrials.gov

clinicaltrials.gov/study/NCT04216563

ABL001 for the Treatment of Chronic Myeloid Leukemia in ...

This phase II trial studies how well ABL001 works in treating patients with chronic myeloid leukemia who are on therapy with tyrosine kinase inhibitor.

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nejm.org

nejm.org/doi/abs/10.1056/NEJMoa2400858

Asciminib in Newly Diagnosed Chronic Myeloid Leukemia

Asciminib showed superior efficacy and a favorable safety profile in patients with newly diagnosed chronic-phase CML.

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC12159473/

The efficacy and safety of asciminib treatment in patients ...

Asciminib is effective in the treatment of patients with CML, and the most common AE during treatment is thrombocytopenia.

7.

ashpublications.org

ashpublications.org/blood/article/144/Supplement%201/479/530697/Efficacy-and-Safety-of-Asciminib-in-Chronic

Efficacy and Safety of Asciminib in Chronic Myeloid Leukemia ...

Results: This interim analysis included 43 pts with CML-CP in 2L who enrolled and received ≥1 dose of asciminib on or before the data cutoff ( ...

8.

onclive.com

onclive.com/view/meta-analysis-highlights-efficacy-safety-benefits-with-asciminib-in-chronic-myeloid-leukemia

Meta-Analysis Highlights Efficacy, Safety Benefits With ...

Asciminib shows superior efficacy and lower adverse effects compared to other TKIs in CP-CML patients, with improved major molecular response ...