Asciminib vs Other TKIs for Chronic Myeloid Leukemia

Not currently recruiting at 167 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

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 early-stage chronic myeloid leukemia (CML). Researchers aim to determine if asciminib is more effective than similar medications, such as imatinib or dasatinib, for newly diagnosed patients. The study includes various phases, with a part where participants might stop treatment if they meet certain conditions. This trial seeks individuals newly diagnosed with CML who have not received other treatments. As a Phase 3 trial, it represents the final step before FDA approval, offering participants an opportunity to contribute to potentially groundbreaking treatment advancements.

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.

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

Research shows that asciminib is generally well-tolerated by patients with chronic myeloid leukemia (CML). Earlier studies identified thrombocytopenia, a low platelet count, as the most common side effect, which can lead to easy bruising or bleeding. However, many patients did not experience severe side effects.

Other drugs like imatinib, nilotinib, dasatinib, and bosutinib, also used to treat CML, have proven safe. The FDA has approved these medications, which are known to cause mostly mild to moderate side effects, such as nausea or tiredness.

Overall, asciminib and the other drugs in this trial are considered safe for most people. Each has been tested in other studies and found to have manageable side effects. Prospective participants should discuss any concerns with a healthcare professional. ^{1 2 3 4 5}

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

Asciminib is unique because it introduces a new mechanism of action for treating Chronic Myeloid Leukemia (CML). Unlike most treatments that target multiple sites, asciminib specifically inhibits the ABL myristoyl pocket, offering a more targeted approach. This specificity not only has the potential to improve treatment efficacy but also helps reduce the risk of side effects commonly associated with other tyrosine kinase inhibitors (TKIs) like imatinib, dasatinib, and nilotinib. Researchers are particularly excited about asciminib because it opens the door to more personalized and potentially more effective treatment options for patients with CML.

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

This trial will compare asciminib with other tyrosine kinase inhibitors (TKIs) for treating Chronic Myeloid Leukemia (CML). Studies have shown that asciminib is highly effective in treating early-stage CML. In a recent large study, asciminib outperformed other common treatments like imatinib, nilotinib, dasatinib, and bosutinib. Patients who took asciminib experienced a significant reduction in cancer cells. Additionally, asciminib generally caused fewer side effects than other treatments, making it a promising choice for newly diagnosed individuals. These findings suggest that asciminib could be a strong option for initial CML treatment. ^{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?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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 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]

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]

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 ...

5. 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. novartis.com novartis.com/us-en/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 ... Asciminib Continues to Provide Superior Efficacy and Favorable Safety and Tolerability vs Tyrosine Kinase Inhibitors In Newly Diagnosed Chronic ...