Asciminib for Chronic Myelogenous Leukemia

Overseen By Elias Jabbour, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Investigational agents

Disqualifiers: Cardiac disease, Psychiatric disorders, 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: Unknown

Duration: 36 months

50 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if asciminib can help manage chronic myelogenous leukemia (CML) and to study its safety and effects. Participants take asciminib daily in tablet form, targeting a specific protein linked to CML. The trial seeks participants diagnosed with CML within the last year who have not received extensive treatment. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on certain cancer treatments or investigational drugs, you may need to stop those before joining the trial.

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

Research shows that asciminib is generally safe and well-tolerated for people with chronic myelogenous leukemia (CML). Studies have demonstrated its effectiveness and safety, with most patients experiencing only mild to moderate side effects, such as nausea or headaches.

The FDA has granted asciminib accelerated approval for newly diagnosed CML patients, reflecting confidence in its safety. During the trial, doctors will closely monitor participants to ensure the treatment remains safe. Participants should discuss any concerns or side effects with the trial team. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for Chronic Myelogenous Leukemia (CML), which often include tyrosine kinase inhibitors like imatinib, dasatinib, and nilotinib, Asciminib stands out because it targets the ABL myristoyl pocket. This unique mechanism of action is different from the typical approach of blocking the ATP-binding site. Researchers are excited because this novel targeting method could potentially overcome resistance issues seen with current treatments and offer a new line of attack against CML. Additionally, Asciminib's oral tablet form, taken once daily, adds convenience for patients, making it an appealing option if proven effective.

What evidence suggests that asciminib might be an effective treatment for CML?

Research has shown that asciminib, the treatment under study in this trial, is a promising option for chronic myelogenous leukemia (CML). In studies, 66% of patients experienced a major molecular response, indicating a significant reduction in cancer markers by week 48, compared to 57.8% with other treatments. Longer-term data also highlight asciminib's superior effectiveness and safety. Additionally, real-world studies confirm its effectiveness and safety, supporting its potential as a reliable treatment option for CML. ^{3 6 7 8 9}

Who Is on the Research Team?

Elias Jabbour, MD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

Adults over 18 with newly diagnosed Chronic Myeloid Leukemia in early phase (diagnosed within the last year) who have good organ function and no severe concurrent conditions. Must not be pregnant or breastfeeding, agree to use contraception, and can't have had extensive prior cancer treatments or certain heart diseases.

Inclusion Criteria

I've had limited treatment with hydroxyurea, cytarabine, or a TKI for less than 30 days.

Ability to understand and the willingness to sign a written informed consent document

I was diagnosed with extra chromosome changes but not in an accelerated phase.

Exclusion Criteria

I am not pregnant or breastfeeding.

History of allergic reactions attributed to compounds of similar chemical or biologic composition to asciminib or other agents used in study

My heart's QT interval is longer than normal.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive asciminib tablets daily for the duration of the study

36 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

What Are the Treatments Tested in This Trial?

Interventions

• Asciminib

Trial Overview

The trial is testing Asciminib's effectiveness and safety for controlling Chronic Myeloid Leukemia in its early stage. It will compare how well patients respond to this drug versus their condition without it.

How Is the Trial Designed?

Group I: Treatment with Asciminib Experimental Treatment 1 Intervention

Participants will take tablets of asciminib by mouth every day on this study. Participants should take it at least 1 hour before and 2 hours after eating. The tablets should be swallowed whole, not crushed.

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 Pharmaceuticals

Industry Sponsor

Trials

2,963

Recruited

4,275,000+

Founded

1996

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Gleevec, Cosentyx, Entresto, Kisqali

Dr. Vas Narasimhan

Novartis Pharmaceuticals

Chief Executive Officer since 2018

MD from Harvard Medical School

Dr. Shreeram Aradhye

Novartis Pharmaceuticals

Chief Medical Officer since 2021

MD

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 a newly FDA-approved treatment for chronic myelogenous leukemia (CML) that specifically targets the myristoyl pocket of the BCR-Abl fusion protein, effectively reducing its kinase activity.

This drug is particularly important for patients with the T315I mutation and is used as a third-line treatment, showcasing its role in managing resistant forms of CML alongside other established therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting BCR-Abl in the treatment of Philadelphia-chromosome positive chronic myelogenous leukemia. Roskoski, R.[2022]

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 (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 1 trial involving 115 patients with chronic myeloid leukemia (CML-CP), asciminib demonstrated long-term efficacy, with 61.3% of patients achieving a major molecular response (MMR) after approximately 4 years of treatment.

While asciminib was generally well-tolerated, common grade ≥3 adverse events included increased pancreatic enzymes (22.6%) and thrombocytopenia (13.9%), but most adverse events occurred in the first year, indicating a manageable safety profile over time.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Asciminib monotherapy in patients with CML-CP without BCR::ABL1 T315I mutations treated with at least two prior TKIs: 4-year phase 1 safety and efficacy results. Mauro, MJ., Hughes, TP., Kim, DW., 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]

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]

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 ...

Median exposure duration was 5.9 (range, 0–8.4) years; 60.9% of patients continued receiving asciminib through post-trial access. Grade ≥3 ...

3.

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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 ...

Novartis today announced positive, longer-term results from the pivotal Phase III ASC4FIRST trial with Scemblix (asciminib) showing superior major molecular ...

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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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pubmed.ncbi.nlm.nih.gov

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Asciminib in Newly Diagnosed Chronic Myeloid Leukemia

The percentage of patients with a major molecular response at week 48 was 66.0% with asciminib and 57.8% with TKIs in the second-generation TKI ...

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scemblix-hcp.com

scemblix-hcp.com/

Ph+ CML-CP | SCEMBLIX® (asciminib) Tablets | HCP

Learn more about SCEMBLIX® (asciminib), a treatment option for adult patients with newly diagnosed or previously treated Ph+ CML-CP.

7.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC7873237/

Safety and efficacy of asciminib treatment in chronic myeloid ...

In conclusion, the results presented, in line with data from the phase 1 study, show asciminib as a safe and efficacious drug for CML patients ...

8.

fda.gov

fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-asciminib-newly-diagnosed-chronic-myeloid-leukemia

FDA grants accelerated approval to asciminib for newly ...

Efficacy and Safety. The efficacy of asciminib for newly diagnosed Ph+ CML in CP was evaluated in ASC4FIRST (NCT04971226), a multicenter, ...

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clinical-lymphoma-myeloma-leukemia.com

clinical-lymphoma-myeloma-leukemia.com/article/S2152-2650(22)01388-X/fulltext

Updated Efficacy and Safety Data From a Phase I Trial

CML-466 Asciminib Provides Durable Molecular Responses in Patients With Chronic Myeloid Leukemia ... safety data in patients with CML-CP with the T315I ...