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

Trial Summary

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.

What data supports the effectiveness of the drug Asciminib for treating chronic myelogenous leukemia?

Research shows that Asciminib is effective for patients with chronic myeloid leukemia who have been treated with at least two other drugs, as it demonstrated better results and fewer side effects compared to another drug, bosutinib. It is especially useful for patients with a specific mutation (T315I) that makes other treatments less effective. ^{1 2 3 4 5}

Is asciminib safe for humans?

Asciminib has been studied in clinical trials for chronic myeloid leukemia and is generally considered safe, with common side effects including low blood platelet levels (thrombocytopenia), low white blood cell levels (neutropenia), and increased pancreatic enzymes. Most side effects were mild to moderate, and the likelihood of new side effects decreased over time. ^{1 2 3 6 7}

How is the drug Asciminib different from other treatments for chronic myelogenous leukemia?

Asciminib is unique because it is the first drug to specifically target the ABL myristoyl pocket, a different site on the BCR-ABL1 protein than other treatments, making it effective against certain resistant forms of chronic myelogenous leukemia. It is taken orally and has shown better safety and efficacy compared to some existing treatments, especially for patients who have tried multiple other therapies. ^{1 2 3 4 6}

What is the purpose of this trial?

To learn if asciminib can help to control CML. The safety and effects of this drug will also be studied.

Research Team

Elias Jabbour, MD

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

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.

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

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

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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 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]

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 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 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]

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]

References

1. England 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. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Asciminib monotherapy for newly diagnosed chronic myeloid leukemia in chronic phase: the ASC4FIRST phase III trial. [2023]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Asciminib: First Approval. [2022]

4. Netherlands pubmed.ncbi.nlm.nih.gov

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

5. England pubmed.ncbi.nlm.nih.gov

An evaluation of asciminib for patients with chronic myeloid leukemia previously treated with ≥2 tyrosine kinase inhibitors. [2022]

6. Japan 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]. [2023]

7. England 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. [2023]