Asciminib vs Nilotinib for Chronic Myeloid Leukemia

(ASC4START Trial)

Not currently recruiting at 166 trial locations

Overseen By Novartis Pharmaceuticals

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Novartis Pharmaceuticals

Must not be taking: Torsades de Pointes risk

Disqualifiers: Cardiac disease, Liver disease, HIV, 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: 4

Duration: Up to approximately 4.5 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to compare the tolerability of two oral medications, asciminib and nilotinib, for treating chronic myeloid leukemia in its chronic phase. Researchers seek to determine which medication patients tolerate better while effectively managing their condition. Those diagnosed with this type of leukemia within the last three months and possessing certain genetic markers might be suitable for this study. Participants will receive either asciminib or nilotinib to evaluate and compare their experiences and outcomes. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to the development of a potentially new treatment option.

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, but it mentions that you cannot take medications with a known risk of causing heart rhythm problems (Torsades de Pointes) unless they can be safely replaced 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. Some studies suggest that asciminib is safer than other treatments. The most common side effect is thrombocytopenia, a lower-than-normal number of platelets in the blood, which can be managed.

For nilotinib, research indicates it is effective and often used as a treatment, but it may cause more side effects. Patients taking nilotinib might experience higher levels of liver enzymes and blood sugar. Doctors monitor these side effects during treatment.

Both drugs have been well-studied and come with some side effects, but many patients handle them without major issues. Always consult a healthcare professional about what to expect and how to manage any side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard of care for chronic myeloid leukemia, which often includes drugs like imatinib and dasatinib, asciminib brings something new to the table. It works differently by targeting the ABL myristoyl pocket, offering a unique mechanism of action compared to traditional treatments that target the ATP-binding site of the BCR-ABL protein. This could potentially lead to fewer side effects and improved outcomes for patients. Researchers are particularly excited because asciminib might overcome resistance seen with other treatments, providing a new hope for those who don't respond well to current options.

What evidence suggests that this trial's treatments could be effective for Chronic Myeloid Leukemia?

This trial will compare Asciminib and Nilotinib for treating chronic-phase chronic myeloid leukemia (CML-CP). Studies have shown that Asciminib, which participants in this trial may receive, works well for treating CML-CP. It has proven effective over the long term and is generally safe, making it a good option for patients. Research also indicates that Asciminib provides better results than other standard treatments, with fewer side effects. Nilotinib, another treatment option in this trial, is also effective for CML-CP and has been used widely. Both treatments have shown strong results, but recent data suggests Asciminib might be more effective and easier to tolerate. ^{1 5 6 7 8}

Who Is on the Research Team?

Novartis Pharmaceuticals

Principal Investigator

Novartis Pharmaceuticals

Are You a Good Fit for This Trial?

Adults (≥18 years) newly diagnosed with Philadelphia Chromosome Positive Chronic Myelogenous Leukemia in chronic phase can join. They must be within 3 months of diagnosis, have an ECOG performance status of 0 or 1, and proper organ function. Excluded are those previously treated for CML (except hydroxyurea/anagrelide), with certain heart conditions, severe concurrent diseases, recent major surgery, other active malignancies within the past 3 years (some exceptions apply), a history of pancreatitis or liver disease, and known HIV/HBV/HCV infections.

Inclusion Criteria

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

My chronic myeloid leukemia matches specific criteria set in 2013.

I am fully active or can carry out light work.

Exclusion Criteria

I have only been treated with hydroxyurea or anagrelide for my CML.

I have a severe illness that is not under control.

I have had pancreatitis before.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either asciminib 80 mg QD or nilotinib 300 mg BID until unacceptable toxicity, disease progression, or at the discretion of the investigator or participants

Up to approximately 4.5 years

Visits every 4 weeks initially, then every 12 weeks

Follow-up

A safety follow-up visit/call is performed approximately 30 days after the end of treatment. Participants who discontinue treatment prematurely are followed up for survival and progression

4 weeks

Long-term follow-up

Participants are monitored for survival and progression to Accelerated Phase/Blast Crisis up until the end of the study

Up to approximately 4.5 years

What Are the Treatments Tested in This Trial?

Interventions

• Asciminib
• Nilotinib

Trial Overview The trial is testing the tolerability and effectiveness of two oral drugs: Asciminib versus Nilotinib in adults with newly diagnosed Ph+ CML-CP. Participants will receive one drug or the other to compare how well they tolerate them and how effective they are at treating their leukemia.

How Is the Trial Designed?

Group I: Asciminib Experimental Treatment 1 Intervention

Participants will receive asciminib 80 mg QD

Group II: Nilotinib Active Control 1 Intervention

Participants will receive nilotinib 300 mg BID

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 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 (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, 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]

Citations

1. 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) ...

2. 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 ...

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. 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.

6. 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 ( ...

7. 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 ... Asciminib Continues to Provide Superior Efficacy and Favorable Safety and Tolerability vs Tyrosine Kinase Inhibitors In Newly Diagnosed Chronic ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12159473/

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.