Asciminib for Chronic Myelogenous Leukemia

Not currently recruiting at 66 trial locations

Overseen By Novartis Pharmaceuticals

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Novartis Pharmaceuticals

Must be taking: Tyrosine kinase inhibitors

Disqualifiers: BCR::ABL1 T315I mutation, Hepatitis B, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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: 144 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called asciminib for individuals with chronic myelogenous leukemia in the chronic phase (CML-CP), a type of blood cancer. Researchers aim to determine the best use of asciminib for patients who have already tried at least two other treatments known as Tyrosine Kinase Inhibitors (TKIs). The trial may suit those with CML-CP who have found multiple TKI treatments ineffective or intolerable. For those meeting these criteria, this trial might be worth considering. As a Phase 3 trial, this treatment is in the final step before FDA approval, offering early access to a potentially effective therapy.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, since the study involves patients who have been treated with Tyrosine Kinase Inhibitors (TKIs), it might be necessary to discuss your current medications with the study team.

Is there any evidence suggesting that asciminib is likely to be safe for humans?

Research has shown that asciminib is generally safe for people with chronic myelogenous leukemia (CML). Studies have found that most patients tolerate it well. For instance, one study reported that asciminib usually does not cause severe side effects. Common side effects are mild, such as fatigue or headaches. Several studies have tested the treatment, supporting its strong safety record. For those who have used other Tyrosine Kinase Inhibitors (TKIs), asciminib might be a suitable option. Always consult your doctor when considering joining a clinical trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for chronic myelogenous leukemia?

Asciminib is unique because it targets the BCR-ABL1 protein in a novel way, binding to a different site compared to traditional tyrosine kinase inhibitors (TKIs) like imatinib, dasatinib, and nilotinib. This innovative mechanism can potentially overcome resistance issues seen with current medications and provide options for patients who have not responded well to existing treatments. Researchers are excited about asciminib because it offers a promising approach to treating chronic myelogenous leukemia by potentially improving effectiveness and tolerability, leading to better outcomes for patients.

What evidence suggests that asciminib might be an effective treatment for chronic myelogenous leukemia?

Research has shown that asciminib effectively treats chronic myelogenous leukemia in its chronic phase (CML-CP). In the ASCEMBL trial, asciminib proved effective over the long term for patients who had already tried other medications. Another study found that asciminib reduced cancer markers in the blood more effectively, indicating its potential. A real-world study from Italy also reported positive results, highlighting its safety and effectiveness. Overall, these findings suggest that asciminib is a promising treatment option for CML-CP, especially for those who have tried other treatments. Participants in this trial will receive asciminib, with the potential for dose escalation based on their response. ^{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 adults with chronic myelogenous leukemia in chronic phase (CML-CP) who have tried at least two Tyrosine Kinase Inhibitors without success or cannot tolerate them. They must not have had a stem-cell transplant, plan to undergo one soon, or have certain heart conditions or severe medical issues.

Inclusion Criteria

My cancer has shown resistance or high-risk changes after starting treatment.

I had low platelet counts due to previous therapy, but it lasted less than 30 days.

< 20% basophils in the peripheral blood

Exclusion Criteria

I have not had a heart attack, chest pain, or heart surgery in the last 6 months.

I do not have Long QT syndrome or a family history of sudden death.

I have had acute pancreatitis in the last year or have chronic pancreatitis.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

Treatment

Participants receive asciminib continuously for up to 144 weeks or until disease progression, treatment failure, or intolerance

144 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Asciminib

Trial Overview

The study aims to find the best dose of asciminib for treating CML-CP after failure with other treatments. Patients will take either 40 mg twice daily or 80 mg once daily of asciminib and their response will be monitored according to specific criteria.

How Is the Trial Designed?

Group I: ABL001 Experimental Treatment 3 Interventions

Participants will be treated with 80 mg of ABL001 (40 mg BID or 80mg QD). In patients not achieving MMR at 48 weeks or losing the response after the week 48 assessment up to week 108, asciminib dose may be escalated to 200 mg q.d. if in the investigator's opinion the patient may benefit from the escalation.

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 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 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 (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 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, 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 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]

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]

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.

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.

5.

nature.com

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

Asciminib monotherapy in patients with chronic myeloid ...

Median exposure duration was 5.9 (range, 0–8.4) years; 60.9% of patients continued receiving asciminib through post-trial access. Grade ≥3 ...

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC7873237/

Safety and efficacy of asciminib treatment in chronic myeloid ...

In conclusion, the results presented, in line with data from the phase 1 study, show asciminib as a safe and efficacious drug for CML patients ...

7.

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.

8.

clinical-lymphoma-myeloma-leukemia.com

clinical-lymphoma-myeloma-leukemia.com/article/S2152-2650(22)01388-X/fulltext

Updated Efficacy and Safety Data From a Phase I Trial

CML-466 Asciminib Provides Durable Molecular Responses in Patients With Chronic Myeloid Leukemia ... safety data in patients with CML-CP with the T315I ...