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

Trial Summary

What is the purpose of this trial?

This is an open label, phase 2 study investigating asciminib in patients previously treated with one line of TKI therapy.

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.

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

Asciminib has shown to be effective in treating chronic myeloid leukemia, especially in patients who have not responded well to other treatments. In a study, it demonstrated better results and fewer side effects compared to another drug, bosutinib, in patients who had already tried at least two other treatments. ^{1 2 3 4 5}

Is asciminib safe for humans?

Asciminib has been shown to have a better safety profile compared to bosutinib, with fewer severe side effects and fewer patients needing to stop treatment due to adverse effects. Common side effects include low platelet counts (thrombocytopenia) and low white blood cell counts (neutropenia). ^{1 2 4 5 6}

How is the drug Asciminib unique in treating chronic myeloid 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 mutations that cause resistance to conventional therapies. ^{1 2 4 5 6}

Research Team

Ghayas Issa, MD

Principal Investigator

The University of Texas MD Anderson Cancer Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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 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 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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

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

2. 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]

3. England pubmed.ncbi.nlm.nih.gov

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

4. 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]

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

Asciminib: First Approval. [2022]

6. United States 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. [2023]