Asciminib + Imatinib for Chronic Myeloid Leukemia

Recruiting at 3 trial locations

Overseen By Ehab L. Atallah

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Medical College of Wisconsin

Must be taking: Tyrosine kinase inhibitors

Must not be taking: Asciminib

Disqualifiers: Accelerated CML, Second malignancy, Pancreatitis, 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

Compensation: Varies

Number of Visits: Unknown

51 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a single arm phase II study that will enroll a minimum of 47 subjects with a maximum of 51. All patients will have a confirmed diagnosis of chronic phase chronic myeloid Leukemia and must have previously attempted to discontinue Tyrosine Kinase inhibitors (TKI). All patients must have restarted the same TKI they were on prior to discontinuation at the time of relapse in order to be eligible for this trial.

Do I need to stop my current medications for the trial?

The trial requires that you continue taking the same Tyrosine Kinase Inhibitor (TKI) you were on before your first attempt to stop treatment. You will need to stay on this medication for at least 12 months during the trial.

What data supports the effectiveness of the drug combination Asciminib and Imatinib for treating Chronic Myeloid Leukemia?

Asciminib has shown strong effectiveness in treating chronic myeloid leukemia, especially in patients who have not responded well to other treatments. In clinical trials, it demonstrated better results and fewer side effects compared to another drug, bosutinib, making it a promising option for patients with limited treatment choices. ^{1 2 3 4 5}

Is the combination of Asciminib and Imatinib safe for treating chronic myeloid leukemia?

Asciminib has shown a good safety profile in clinical trials for chronic myeloid leukemia, with common side effects including fatigue, low platelet counts, and anemia. It has fewer severe side effects compared to some other treatments, and no cardiovascular events were reported in one study. ^{1 2 5 6 7}

How is the drug Asciminib + Imatinib unique for treating chronic myeloid leukemia?

Asciminib is a novel drug that targets a specific part of the BCR::ABL1 protein, known as the ABL myristoyl pocket, which is different from other treatments that target the ATP-binding site. This unique mechanism allows it to be effective in patients who have developed resistance or intolerance to other tyrosine kinase inhibitors, offering a new option for those with limited treatment choices. ^{1 2 4 5 8}

Research Team

Ehab L. Atallah

Principal Investigator

Medical College of Wisconsin

Michael J. Mauro, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

Adults diagnosed with chronic phase chronic myeloid leukemia (CP-CML) who have tried to stop taking imatinib once before but relapsed. They must be on imatinib again, agree to use two contraception methods if of childbearing potential, and meet specific health criteria including a stable molecular response for over two years and an ECOG performance status of 0-3.

Inclusion Criteria

Must have met all the following criteria prior to first attempt to discontinue their imatinib:

I have chronic phase CML with a specific protein variant.

- If they are of childbearing potential, agree to practice two effective methods of contraception from the time of signing of the informed consent form through 90 days after the last dose of study drug

Exclusion Criteria

I can care for myself but may not be able to do heavy physical work.

Any serious medical or psychiatric illness that could, in the investigator's opinion, interfere with the completion of treatment according to this protocol

I have completed 12 cycles of combination therapy.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Combination Treatment

Participants receive asciminib in combination with a TKI for 12 cycles

12 months

Monthly visits for each cycle

Treatment-Free Remission (TFR)

Participants discontinue TKI and are monitored off treatment

3 years

Regular central PCR testing during the first two years

Follow-up

Participants are monitored for safety and effectiveness after TFR phase

1 year

Treatment Details

Interventions

• Asciminib
• Imatinib

Trial Overview The trial is testing the combination therapy of Asciminib plus Imatinib in patients with CP-CML who previously relapsed after stopping treatment. It's a single-arm phase II study aiming for 41-51 participants to see if this combo can allow them to achieve treatment-free remission.

Participant Groups

Group I: Asciminib 80 mg daily plus dasatinib (maximum dose of 100 mg PO once daily) Experimental Treatment 2 Interventions

All eligible patients will begin a combination of asciminib in combination with a TKI cycle 1 day 1 in the combination treatment phase. They will continue combination therapy for a total of 12 cycles (minimum of 12 months). At the end of 12 cycles asciminib will be discontinued and any patient who has met the criteria for the treatment free remission (TFR) screening phase will enter into the TFR phase. Once in the TFR phase, patients will discontinue their TKI and be monitored off treatment.

Group II: Asciminib 40 mg twice daily plus nilotinib (maximum dose of 300 mg twice daily) Experimental Treatment 2 Interventions

All eligible patients will begin a combination of asciminib in combination with a TKI cycle 1 day 1 in the combination treatment phase. They will continue combination therapy for a total of 12 cycles (minimum of 12 months). At the end of 12 cycles asciminib will be discontinued and any patient who has met the criteria for the treatment free remission (TFR) screening phase will enter into the TFR phase. Once in the TFR phase, patients will discontinue their TKI and be monitored off treatment.

Group III: Asciminib 40 mg PO daily plus imatinib (maximum dose of 400 mg PO once daily) Experimental Treatment 2 Interventions

All eligible patients will begin a combination of asciminib in combination with a TKI cycle 1 day 1 in the combination treatment phase. They will continue combination therapy for a total of 12 cycles (minimum of 12 months). At the end of 12 cycles asciminib will be discontinued and any patient who has met the criteria for the treatment free remission (TFR) screening phase will enter into the TFR phase. Once in the TFR phase, patients will discontinue their TKI and be monitored off treatment.

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?

Medical College of Wisconsin

Lead Sponsor

Trials

645

Recruited

1,180,000+

H. Jean Khoury Cure CML Consortium

Collaborator

Trials

3

Recruited

80+

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, 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 an allosteric inhibitor specifically designed for patients with chronic phase chronic myeloid leukemia (CP-CML) who are resistant or intolerant to at least two prior tyrosine kinase inhibitors (TKIs), showing a favorable safety profile and strong efficacy in clinical trials.

In a phase 3 trial, asciminib demonstrated a significantly higher major molecular response rate and lower discontinuation rate compared to bosutinib in patients with CP-CML who had previously failed two TKIs, indicating its potential as a more effective treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Asciminib: the first-in-class allosteric inhibitor of BCR::ABL1 kinase. Choi, EJ.[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 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 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, a new treatment for chronic myeloid leukemia (CML), shows a good safety profile with a lower rate of adverse effects compared to previous tyrosine kinase inhibitors (TKIs), with 55% of patients reporting side effects and only 18% experiencing severe effects.

Despite its unique mechanism of action, asciminib does carry a risk of cross-toxicity with traditional TKIs, particularly for side effects like thrombocytopenia and anemia, indicating careful monitoring is still necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toxicity of Asciminib in Real Clinical Practice: Analysis of Side Effects and Cross-Toxicity with Tyrosine Kinase Inhibitors. Pérez-Lamas, L., Luna, A., Boque, C., et al.[2023]

Asciminib is a newly approved treatment for chronic-phase chronic myeloid leukemia (CML) patients who have not responded to two previous therapies or have the T315I mutation, showcasing its role as a third-line option.

This drug is notable for its high specificity and potency against the BCR::ABL1 kinase, making it effective against most mutations in the kinase domain, and it may be used in combination with other therapies, providing clinicians with more treatment choices.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Asciminib: a new therapeutic option in chronic-phase CML with treatment failure. Yeung, DT., Shanmuganathan, N., Hughes, TP.[2022]

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. 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]

3. Korea (South) pubmed.ncbi.nlm.nih.gov

Asciminib: the first-in-class allosteric inhibitor of BCR::ABL1 kinase. [2023]

4. England pubmed.ncbi.nlm.nih.gov

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

5. 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]

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]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Toxicity of Asciminib in Real Clinical Practice: Analysis of Side Effects and Cross-Toxicity with Tyrosine Kinase Inhibitors. [2023]

8. United States pubmed.ncbi.nlm.nih.gov

Asciminib: a new therapeutic option in chronic-phase CML with treatment failure. [2022]