Asciminib for Chronic Myeloid Leukemia

(ASC2ESCALATE Trial)

Not currently recruiting at 113 trial locations

Overseen By Novartis Pharmaceuticals

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Novartis Pharmaceuticals

Must be taking: TKIs

Must not be taking: CYP3A inducers, inhibitors

Disqualifiers: Cardiac issues, Pancreatitis, Pregnancy, 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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 156 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 myeloid leukemia in its chronic phase (CML-CP). The goal is to evaluate asciminib's effectiveness for those who have encountered issues with previous treatments or are newly diagnosed with minimal exposure to other treatments. Participants should have CML-CP that hasn't progressed to more severe stages and may have experienced treatment failure or intolerance with their first medication. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important advancements in CML-CP treatment.

Will I have to stop taking my current medications?

The trial requires that certain medications be stopped or switched at least one week before starting the study treatment. Specifically, medications that strongly affect the enzyme CYP3A must be replaced with alternatives. If you are taking any medications with a known risk of causing heart rhythm issues, they must also be discontinued or replaced 7 days before starting the study drug.

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 myeloid leukemia (CML). Studies have found that most patients tolerate it well. Longer-term evidence supports that asciminib not only works effectively but also has fewer side effects compared to other treatments for this condition.

In past research, patients using asciminib did not experience any new or worsening safety issues over time, indicating that the treatment remains consistently safe and reliable. Overall, asciminib is a promising option with a history of being well-tolerated by those who have used it. ^{1 2 3 4 5}

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

Researchers are excited about asciminib for treating chronic myeloid leukemia (CML) because it offers a new mechanism of action compared to standard treatments. Most current options, like tyrosine kinase inhibitors (TKIs), work by targeting the BCR-ABL1 protein to inhibit cancer cell growth. However, asciminib is unique as it specifically targets the myristoyl pocket of the BCR-ABL1 protein, which may offer a more precise way to inhibit the cancer cells with potentially fewer side effects. This distinct approach provides hope for more effective and tolerable treatment options for patients with CML.

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

Studies have shown that asciminib effectively treats chronic myeloid leukemia (CML) in its early stage. In a real-world study with 77 patients, asciminib produced promising results for those who had previously tried other treatments. It outperformed other standard treatments for CML, helping patients respond more positively. Another analysis highlighted that asciminib not only works better but also causes fewer side effects compared to other common treatments. Overall, these findings suggest that asciminib could be a strong option for managing CML. Participants in this trial will receive an initial oral dose of 80 mg of asciminib, with possible dose escalation. ^{2 6 7 8 9}

Who Is on the Research Team?

Novartis

Principal Investigator

Novartis

Are You a Good Fit for This Trial?

This trial is for adults with chronic myeloid leukemia who have either failed or couldn't tolerate their first treatment, or are newly diagnosed and treated briefly. They should be in good physical condition, not in the advanced stages of leukemia, and without serious heart issues or a history of certain other cancers.

Inclusion Criteria

I experienced severe side effects from my cancer treatment that didn't improve with changes.

I've had severe blood-related side effects from treatment, even after the dose was lowered.

My BCR-ABL1 levels are above 10% after 6-12 months of first-line treatment.

Exclusion Criteria

I have received previous treatment.

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

I am not taking any strong drugs that affect liver enzymes with my 200 mg twice daily medication.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

Treatment

Participants receive asciminib with possible dose escalation based on response

156 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 Asciminib (Scemblix) is being tested as a solo treatment for chronic myeloid leukemia. The study will include patients previously treated with one TKI drug that didn't work well or caused side effects, as well as new patients who've had minimal prior treatment.

How Is the Trial Designed?

Group I: Asciminib Experimental Treatment 1 Intervention

80 mg initial oral dose taken once a day with possible dose 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 (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 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 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, 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]

Citations

1. 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.

2. 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 ...

3. 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) ...

4. 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 ...

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

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38820078/

Asciminib in Newly Diagnosed Chronic Myeloid Leukemia Asciminib showed superior efficacy and a favorable safety profile in patients with newly diagnosed chronic-phase CML.

8. clinicaltrials.gov clinicaltrials.gov/study/NCT02081378

A Phase I Study of Oral Asciminib (ABL001) in Patients ... The design of a phase I, open label, dose finding study was chosen in order to establish a safe and tolerated dose of single agent ABL001 in Chronic myeloid ...

9. 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 ... The safety profile of asciminib is consistent with the current established safety profile, with no new or worsening safety concerns. The ...