Asciminib Continuation for Chronic Myelogenous Leukemia

Recruiting at 112 trial locations

Overseen By Novartis Pharmaceuticals

Age: Any Age

Sex: Any

Trial Phase: Phase 4

Sponsor: Novartis Pharmaceuticals

Must be taking: Asciminib, Imatinib, Nilotinib, Bosutinib

Disqualifiers: Pregnancy, Unresolved toxicities, QTcF>480msec, 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

Duration: 8 years

347 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial focuses on understanding the long-term safety of asciminib for individuals with chronic myelogenous leukemia (CML) who have participated in previous Novartis studies. It examines the effects of asciminib alone and in combination with other treatments such as bosutinib, dasatinib, imatinib, and nilotinib. Suitable candidates have CML or acute lymphoblastic leukemia (ALL) and are currently receiving these treatments in a Novartis-sponsored study, with the investigator believing they would benefit from continued participation. As a Phase 4 trial, this research aims to understand how an FDA-approved and effective treatment can benefit more patients.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop your current medications. However, it seems you can continue taking asciminib or other related medications if you are already on them as part of a previous study.

What is the safety track record for these treatments?

Research has shown that asciminib, whether used alone or with other drugs like dasatinib, imatinib, or nilotinib, is generally well-tolerated. In many studies, patients using asciminib reported fewer side effects compared to those taking other treatments for chronic myeloid leukemia (CML). Specifically, one study found that asciminib caused fewer serious side effects than other treatments. Common side effects were mild, such as headaches or tiredness.

Asciminib is already approved in over 70 countries for treating certain types of CML, suggesting that experts consider it safe based on extensive research. If side effects occur, they are usually not severe. Bosutinib, dasatinib, imatinib, and nilotinib are also well-known treatments with established safety records and are often used as standard care for CML.

Overall, the safety data supports the use of these treatments, indicating they are generally safe for people, with manageable side effects. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about asciminib for treating chronic myelogenous leukemia (CML) because it offers a novel mechanism of action. Unlike traditional treatments like imatinib, dasatinib, and nilotinib that target multiple pathways, asciminib specifically inhibits the Abl myristoyl pocket, which may offer more precise targeting of leukemia cells. This unique approach could potentially lead to fewer side effects and improved outcomes for patients. Additionally, the versatility of asciminib, whether used alone or in combination with other drugs like dasatinib, allows for flexible treatment strategies tailored to individual patient needs.

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

Research has shown that asciminib effectively treats chronic myeloid leukemia (CML). In this trial, participants may receive asciminib alone or with other treatments. Studies have found that asciminib can provide a lasting, long-term response in patients who have tried other treatments before. For instance, one study found that asciminib was more effective and safer than bosutinib, another drug for CML. Participants in this trial may also receive asciminib with dasatinib, imatinib, or nilotinib, which has shown effectiveness but may cause more side effects. Overall, asciminib helps control CML by maintaining a major molecular response, an important measure of treatment success. ^{1 3 6 7 8}

Who Is on the Research Team?

Novartis Pharmaceuticals

Principal Investigator

Novartis Pharmaceuticals

Are You a Good Fit for This Trial?

This trial is for patients with certain types of leukemia (CML or ALL) who are already participating in a Novartis-sponsored study and taking asciminib alone or with other drugs like imatinib, nilotinib, dasatinib, or bosutinib. They should have followed the previous study's rules well and must be seen by their doctor as likely to benefit from continuing treatment.

Inclusion Criteria

I have followed all requirements in a previous study and can do so for this one too.

I am currently being treated with specific drugs for my leukemia and my doctor thinks I should continue.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive continued treatment with asciminib or other therapies as per their previous study regimen

8 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

30 days

What Are the Treatments Tested in This Trial?

Interventions

• Asciminib
• Asciminib single agent
• Bosutinib
• Dasatinib
• Imatinib
• Nilotinib

Trial Overview The trial is focused on long-term safety for those continuing treatment with asciminib, either as a single agent or combined with other leukemia medications such as imatinib, nilotinib, dasatinib, or bosutinib after completing an earlier Novartis-sponsored study.

How Is the Trial Designed?

Group I: Nilotinib single agent group Experimental Treatment 1 Intervention

Participants with CML-CP, from Novartis sponsored asciminib study CABL001E2201 and CABL001J12302 that were receiving nilotinib

Group II: Imatinib single agent group Experimental Treatment 1 Intervention

Participants with CML-CP, from Novartis sponsored asciminib study CABL001E2201 that were receiving imatinib

Group III: Dasatinib-Asciminib switch group Experimental Treatment 1 Intervention

Participants with CML-CP, from Novartis sponsored asciminib study CABL001A2202 that were receiving best available therapy (dasatinib) and switched to asciminib when entering this study or during the course of this study

Group IV: Dasatinib single agent group Experimental Treatment 1 Intervention

Participant with CML-CP , from Novartis sponsored asciminib study CABL001A2202, CABL001J12301, that were receiving Dasatinib.

Group V: Bosutinib-Asciminib switch group Experimental Treatment 1 Intervention

Participants with CML-CP, from Novartis sponsored asciminib study CABL001A2301 that were receiving bosutinib treatment and switched to asciminib when entering this study or during the course of this study

Group VI: Bosutinib single agent group Experimental Treatment 1 Intervention

Participants with CML-CP, from Novartis sponsored asciminib study CABL001A2301, that were receiving bosutinib

Group VII: Asciminib single agent group Experimental Treatment 1 Intervention

Participants with CML or ALL, from Novartis sponsored asciminib studies, including but not limited to CABL001A2301, CABL001A2302, CABL001X2101, CABL001A2202, CABL001AUS04 and CABL001AUS08 studies, that were receiving asciminib

Group VIII: Asciminib single agent formulation for Pediatric Experimental Treatment 1 Intervention

Participants with CML, from Novartis sponsored asciminib studies, including but not limited to CABL001I12201 study, that were receiving asciminib

Group IX: Asciminib in combination with nilotinib group Experimental Treatment 2 Interventions

Participants with CML or ALL from Novartis sponsored asciminib studies CABL001E2201or CABL001X2101 that were receiving asciminib combined with nilotinib

Group X: Asciminib in combination with imatinib group Experimental Treatment 1 Intervention

Participants with CML from Novartis sponsored asciminib studies CABL001E2201 or CABL001X2101 that were receiving asciminib combined with imatinib

Group XI: Asciminib in combination with dasatinib group Experimental Treatment 1 Intervention

Participants with CML from Novartis sponsored study CABL001X2101 that were receiving asciminib with dasatinib

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?

Novartis Pharmaceuticals

Lead 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 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 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 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]

In a phase 3 study involving 233 patients with chronic myeloid leukemia resistant to multiple treatments, asciminib demonstrated a significantly higher major molecular response (MMR) rate at week 24 (25.5%) compared to bosutinib (13.2%), indicating better efficacy.

Asciminib also showed a more favorable safety profile, with fewer severe adverse events (50.6% vs 60.5%) and lower rates of treatment discontinuation due to side effects (5.8% vs 21.1%) compared to bosutinib.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 3, open-label, randomized study of asciminib, a STAMP inhibitor, vs bosutinib in CML after 2 or more prior TKIs. Réa, D., Mauro, MJ., Boquimpani, C., 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]

Citations

1. nejm.org nejm.org/doi/full/10.1056/NEJMoa2400858

Asciminib in Newly Diagnosed Chronic Myeloid Leukemia Asciminib was associated with durable, long-term efficacy and safety in previously treated patients with chronic-phase CML in the ASCEMBL trial ...

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/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 ...

4. nature.com nature.com/articles/s41375-025-02578-7

Asciminib monotherapy in patients with chronic myeloid ... The results of this analysis are consistent with the previous analysis and demonstrated that long-term asciminib provides durable efficacy, is ...

5. 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 ...

6. 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/PMC12055594/

Asciminib monotherapy in patients with chronic myeloid ... Reported here is the final analysis from the phase 1 trial (NCT02081378) [34] assessing the long-term safety, tolerability, and antileukemic ...

8. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/475/531294/Asciminib-ASC-Demonstrates-Favorable-Safety-and

Asciminib (ASC) Demonstrates Favorable Safety and ... Asciminib (ASC) demonstrates favorable safety and tolerability compared with each investigator-selected tyrosine kinase inhibitor (IS TKI) in newly diagnosed ...