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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment combination for individuals with chronic myeloid leukemia, a type of blood cancer. The study tests the effectiveness of combining asciminib, a potential new drug, with various TKIs such as imatinib, nilotinib, or dasatinib, to help patients achieve stable remission. Participants should have previously attempted to stop taking TKIs but had to restart due to a relapse. This trial targets those currently back on the same TKI used when their condition relapsed. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that asciminib, a treatment for chronic myeloid leukemia (CML), is generally safe and well-tolerated. Various studies have identified thrombocytopenia, or low platelet count, as the most common side effect. However, patients have managed side effects and continued treatment. Asciminib's approval in over 70 countries indicates a strong safety record.

When combined with other drugs like imatinib, nilotinib, or dasatinib, asciminib remains safe. These combinations may offer new options for patients who do not respond well to other treatments. Studies have shown that asciminib, whether used alone or with these medications, maintains a good safety record over time.

Participants in these studies have tolerated the treatments well, with most side effects being mild to moderate. Ongoing research continues to support asciminib's safety in treating CML. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because asciminib offers a novel approach for treating Chronic Myeloid Leukemia (CML). Unlike traditional tyrosine kinase inhibitors (TKIs) like imatinib, dasatinib, and nilotinib, which target the ATP-binding site of the BCR-ABL protein, asciminib targets the myristoyl pocket of the same protein. This unique mechanism can potentially overcome resistance issues associated with current therapies. Additionally, combining asciminib with other TKIs may enhance treatment effectiveness, offering hope for improved outcomes in CML patients.

What evidence suggests that this trial's treatments could be effective for chronic myeloid leukemia?

Research has shown that asciminib, one of the treatments in this trial, holds promise for treating chronic myeloid leukemia (CML) when used alone or with other medications. Studies have found that asciminib works better and causes fewer side effects than other common treatments. In this trial, participants may receive asciminib combined with imatinib, which has consistently led to high response rates in patients. Other participants may receive asciminib with nilotinib or dasatinib, which has proven easier for patients to tolerate and provides lasting results. These findings suggest that asciminib, by itself or with other drugs, could be an effective treatment option for CML. ^{1 3 6 7 8}

Who Is on the Research Team?

Ehab L. Atallah

Principal Investigator

Medical College of Wisconsin

Michael J. Mauro, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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 asciminib plus/minus TKI on cycle 1 day 1 of the consolidation phase. They will continue therapy for a total of 12 cycles (minimum of 12 months). Each cycle will be \~28 days. At the end of 12 cycles, asciminib plus/minus TKI will be discontinued in patients who continue to satisfy the requirements for TFR attempt.

Group II: Asciminib 80 mg PO daily taken alone Experimental Treatment 1 Intervention

All eligible patients will begin asciminib plus/minus TKI on cycle 1 day 1 of the consolidation phase. They will continue therapy for a total of 12 cycles (minimum of 12 months). Each cycle will be \~28 days. At the end of 12 cycles, asciminib plus/minus TKI will be discontinued in patients who continue to satisfy the requirements for TFR attempt.

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

All eligible patients will begin asciminib plus/minus TKI on cycle 1 day 1 of the consolidation phase. They will continue therapy for a total of 12 cycles (minimum of 12 months). Each cycle will be \~28 days. At the end of 12 cycles, asciminib plus/minus TKI will be discontinued in patients who continue to satisfy the requirements for TFR attempt.

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

All eligible patients will begin asciminib plus/minus TKI on cycle 1 day 1 of the consolidation phase. They will continue therapy for a total of 12 cycles (minimum of 12 months). Each cycle will be \~28 days. At the end of 12 cycles, asciminib plus/minus TKI will be discontinued in patients who continue to satisfy the requirements for TFR attempt.

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+

Published Research Related to This Trial

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]

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), 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 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 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), 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 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 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]

Citations

1.

nejm.org

nejm.org/doi/full/10.1056/NEJMoa2400858

Asciminib in Newly Diagnosed Chronic Myeloid Leukemia

Here we report the primary results of ASC4FIRST, a pivotal phase 3, randomized trial assessing the efficacy and safety of asciminib as compared ...

2.

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) ...

3.

novartis.com

novartis.com/news/media-releases/novartis-scemblix-phase-iii-data-first-show-superior-efficacy-favorable-safety-and-tolerability-profile-vs-standard-care-tkis-adults-newly-diagnosed-cml

Novartis Scemblix® Phase III data first to show superior ...

Scemblix is the first CML treatment to show significantly better efficacy compared to investigator-selected standard-of-care TKIs.

4.

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 ...

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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 ( ...

6.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/40510784/

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.

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.

8.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC12055594/

Asciminib monotherapy in patients with chronic myeloid ...

Asciminib is approved in > 70 countries for patients with CML-CP after ≥ 2 TKIs and for patients with BCR::ABL1T315I in some countries [33].