Asciminib vs Other TKIs for Chronic Myeloid Leukemia

Recruiting at 143 trial locations

Overseen By Habte Yimer

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Novartis Pharmaceuticals

Must be taking: Tyrosine kinase inhibitors

Must not be taking: Torsades de Pointes risk drugs

Disqualifiers: CNS infiltration, Cardiac issues, 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

Compensation: Varies

Number of Visits: Unknown

Duration: 5 years

406 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a new drug called asciminib against other existing treatments for adults newly diagnosed with a specific type of leukemia. The goal is to see if asciminib is more effective at blocking a protein that helps cancer cells grow. Asciminib has shown superior efficacy in patients with chronic myeloid leukemia (CML) previously treated with multiple other treatments.

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

The trial does not specify if you need to stop taking your current medications. However, if you are on medications with a known risk of causing heart rhythm issues, you may need to stop or replace them 7 days before starting the study drug.

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

Research shows that Asciminib is more effective and safer than bosutinib for patients with chronic myeloid leukemia who have already tried at least two other treatments. In a study, 37.6% of patients taking Asciminib achieved a significant reduction in cancer cells compared to 15.8% of those taking bosutinib, and fewer patients experienced severe side effects with Asciminib. ^{1 2 3 4 5}

What is the safety profile of Asciminib for chronic myeloid leukemia?

Asciminib has shown a good safety profile in clinical trials for chronic myeloid leukemia, with fewer severe side effects compared to other treatments like bosutinib. Common side effects include fatigue, low platelet counts, and anemia, but serious heart-related issues were not observed. ^{1 2 3 4 6}

What makes the drug Asciminib unique for treating chronic myeloid leukemia?

Asciminib is unique because it is the first drug to specifically target the ABL myristoyl pocket, offering a new mechanism of action for treating chronic myeloid leukemia, especially in patients who have not responded well to other treatments. It has shown superior efficacy and safety compared to bosutinib, making it a promising option for patients who have tried at least two other tyrosine kinase inhibitors. ^{1 2 3 4 7}

Research Team

Novartis Pharmaceuticals

Principal Investigator

Novartis Pharmaceuticals

Eligibility Criteria

Adults over 18 with newly diagnosed Ph+ CML-CP within the last 3 months, who haven't been treated for it yet. They must have normal or correctable levels of certain blood elements and organ functions, no severe heart issues or other serious medical conditions, and an ECOG performance status of 0 or 1.

Inclusion Criteria

I was diagnosed with chronic myeloid leukemia in the chronic phase less than 3 months ago.

My leukemia is in the chronic phase and has been confirmed to have the Philadelphia chromosome.

Ability to provide written informed consent prior to any study-related screening procedures being performed

Exclusion Criteria

My heart function is not normal, or I have an abnormal heart rhythm.

I haven't had any other cancer except for certain types in the last 3 years.

I have a history of serious bleeding problems not related to cancer.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either asciminib or an Investigator selected TKI for the treatment of Ph+ CML-CP

5 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

Treatment Details

Interventions

• Asciminib
• Bosutinib
• Dasatinib
• Imatinib
• Nilotinib

Trial Overview The trial is testing Asciminib (80 mg daily) against other TKIs chosen by the investigator: Imatinib (400 mg daily), Nilotinib (300 mg twice a day), Dasatinib (100 mg daily), or Bosutinib (400 mg daily). It aims to find out which treatment works best for new CML-CP patients.

Participant Groups

Group I: Asciminib Experimental Treatment 1 Intervention

Patients will take asciminib 80 mg QD under fasting conditions on ongoing basis; Patients will be randomized 1:1 asciminib versus Investigator selected TKIs

Group II: Investigator selected TKIs Active Control 4 Interventions

Patients will take on ongoing basis the Investigator selected TKIs that will include one of the below treatments: Imatinib 400 mg QD administered with food Nilotinib 300 mg BID administered under fasting conditions Dasatinib 100 mg QD administered with or without a meal Bosotunib 400 mg QD administered with food

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

Findings from Research

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 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]

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 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), 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]

References

1. 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]

2. England pubmed.ncbi.nlm.nih.gov

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

3. 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]

4. United States 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. [2023]

5. England pubmed.ncbi.nlm.nih.gov

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

6. 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]

7. Italy pubmed.ncbi.nlm.nih.gov

Asciminib in chronic myeloid leukemia: a STAMP for expedited delivery? [2023]