Asciminib Continuation for Chronic Myelogenous Leukemia
Recruiting in Palo Alto (17 mi)
+80 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 4
Recruiting
Sponsor: Novartis Pharmaceuticals
Must be taking: Asciminib, Imatinib, Nilotinib, Bosutinib
Disqualifiers: Pregnancy, Unresolved toxicities, QTcF>480msec, others
No Placebo Group
Prior Safety Data
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?This is a long term safety study for patients who have completed a Novartis sponsored asciminib study and are judged by the investigator to benefit from continued treatment
Will I have to stop taking my current medications?
The trial does not specify if you need to stop your current medications. However, it seems you can continue taking asciminib or other related medications if you are already on them as part of a previous study.
What data supports the effectiveness of the drug Asciminib for treating chronic myelogenous leukemia?
Asciminib has shown superior effectiveness compared to bosutinib in patients with chronic myeloid leukemia who have been treated with at least two prior tyrosine kinase inhibitors, with a higher major molecular response rate and better safety profile. It specifically targets a unique site on the BCR::ABL1 protein, which is involved in the disease, and has been approved for use in patients resistant or intolerant to previous therapies.
12345Is asciminib safe for humans?
Asciminib has been shown to have a favorable safety profile in clinical trials for chronic myeloid leukemia, with fewer severe side effects and treatment discontinuations compared to bosutinib, another treatment option. Common side effects include low platelet counts and low white blood cell counts, but overall, it is considered safe for use in patients who have tried other treatments.
14567What 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 to other treatments. It has shown superior efficacy and safety compared to other drugs like bosutinib, making it a promising option for patients with limited treatment choices.
14578Eligibility Criteria
This trial is for patients with certain types of leukemia (CML or ALL) who are already participating in a Novartis-sponsored study and taking asciminib alone or with other drugs like imatinib, nilotinib, dasatinib, or bosutinib. They should have followed the previous study's rules well and must be seen by their doctor as likely to benefit from continuing treatment.Inclusion Criteria
I have followed all requirements in a previous study and can do so for this one too.
I am currently being treated with specific drugs for my leukemia and my doctor thinks I should continue.
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive continued treatment with asciminib or other therapies as per their previous study regimen
8 years
Follow-up
Participants are monitored for safety and effectiveness after treatment
30 days
Participant Groups
The trial is focused on long-term safety for those continuing treatment with asciminib, either as a single agent or combined with other leukemia medications such as imatinib, nilotinib, dasatinib, or bosutinib after completing an earlier Novartis-sponsored study.
10Treatment groups
Experimental Treatment
Group I: Nilotinib single agent groupExperimental Treatment1 Intervention
Participants with CML-CP, from Novartis sponsored asciminib study CABL001E2201 and CABL001J12302 that were receiving nilotinib
Group II: Imatinib single agent groupExperimental Treatment1 Intervention
Participants with CML-CP, from Novartis sponsored asciminib study CABL001E2201 that were receiving imatinib
Group III: Dasatinib-Asciminib switch groupExperimental Treatment1 Intervention
Participants with CML-CP, from Novartis sponsored asciminib study CABL001A2202 that were receiving best available therapy (dasatinib) and switched to asciminib when entering this study or during the course of this study
Group IV: Dasatinib single agent groupExperimental Treatment1 Intervention
Participant with CML-CP , from Novartis sponsored asciminib study CABL001A2202, CABL001J12301, that were receiving Dasatinib.
Group V: Bosutinib-Asciminib switch groupExperimental Treatment1 Intervention
Participants with CML-CP, from Novartis sponsored asciminib study CABL001A2301 that were receiving bosutinib treatment and switched to asciminib when entering this study or during the course of this study
Group VI: Bosutinib single agent groupExperimental Treatment1 Intervention
Participants with CML-CP, from Novartis sponsored asciminib study CABL001A2301, that were receiving bosutinib
Group VII: Asciminib single agent groupExperimental Treatment1 Intervention
Participants with CML or ALL, from Novartis sponsored asciminib studies, including but not limited to CABL001A2301, CABL001A2302, CABL001X2101, CABL001A2202, CABL001AUS04 and CABL001AUS08 studies, that were receiving asciminib
Group VIII: Asciminib in combination with nilotinib groupExperimental Treatment2 Interventions
Participants with CML or ALL from Novartis sponsored asciminib studies CABL001E2201or CABL001X2101 that were receiving asciminib combined with nilotinib
Group IX: Asciminib in combination with imatinib groupExperimental Treatment1 Intervention
Participants with CML from Novartis sponsored asciminib studies CABL001E2201 or CABL001X2101 that were receiving asciminib combined with imatinib
Group X: Asciminib in combination with dasatinib groupExperimental Treatment1 Intervention
Participants with CML from Novartis sponsored study CABL001X2101 that were receiving asciminib with dasatinib
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
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Michigan Medicine University of MichiganAnn Arbor, MI
Oregon Health and Science UniversityPortland, OR
University of Texas MD Anderson Cancer CenterHouston, TX
Novartis Investigative SiteMontreal, Canada
More Trial Locations
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Who Is Running the Clinical Trial?
Novartis PharmaceuticalsLead Sponsor
References
Asciminib monotherapy for newly diagnosed chronic myeloid leukemia in chronic phase: the ASC4FIRST phase III trial. [2023]Asciminib is the first BCR::ABL1 inhibitor that works by Specifically Targeting the ABL Myristoyl Pocket (STAMP). Asciminib has shown favorable efficacy and safety in patients with chronic myeloid leukemia in chronic phase without the T315I mutation who have received ≥2 prior tyrosine kinase inhibitors (TKIs) in phase I and III clinical trials and in patients with the T315I mutation who have received ≥1 prior TKI in phase I. ASC4FIRST (NCT04971226) is a phase III, multicenter, open-label, randomized study of asciminib versus investigator-selected TKI in patients with newly diagnosed chronic myeloid leukemia in chronic phase. The primary end point is major molecular response at week 48. Secondary end points include responses at and by scheduled time points, safety, pharmacokinetics and patient-reported outcomes. Clinical Trial Registration: NCT04971226 (ClinicalTrials.gov).
An evaluation of asciminib for patients with chronic myeloid leukemia previously treated with ≥2 tyrosine kinase inhibitors. [2022]To date, five tyrosine kinase inhibitors (TKIs) are available for treating chronic myeloid leukemia (CML) patients in clinical practice. Despite this, a significant proportion of patients will ultimately develop failure to approved TKIs due to intolerance or resistance. Consequently, new treatment approaches are still required in this unmet clinical need. Asciminib, a first-in-class BCR::ABL1 inhibitor Specifically Targeting the ABL Myristoyl Pocket (STAMP), has the potential to overcome resistance/intolerance to prior TKI treatment.
Targeting BCR-Abl in the treatment of Philadelphia-chromosome positive chronic myelogenous leukemia. [2022]Chronic myelogenous leukemia (CML) is an indolent malignant hematological disease that accounts for about 15% of all cases of leukemia. This disorder results from the formation of the Philadelphia chromosome that involves a reciprocal translocation that produces a lengthened chromosome 9 and shortened chromosome 22 - the Philadelphia chromosome. As a consequence of the translocation, the dysregulated BCR-Abl fusion oncoprotein is formed and it produces the abnormal proliferation of white blood cells. The treatment of CML with imatinib revolutionized the treatment of this disorder and led to the discovery and development of dozens of effective targeted protein kinase inhibitors. Imatinib (first generation), dasatinib, nilotinib, and bosutinib (second generation) have been FDA-approved for frontline therapy, and ponatinib (third generation) is approved for resistant disease with a T315I mutation. Each of these drugs is orally bioavailable. The BCR-Abl fusion protein lacks the physiological N-terminal myristoyl group that binds to a hydrophobic pocket in the large protein kinase lobe and inhibits enzyme activity. The absence of the myristoyl group leads to enhanced protein kinase catalytic activity. Asciminib was designed to bind to this binding pocket to reduce Abl kinase activity. Asciminib is orally effective and was FDA-approved as a third-line treatment for CML and a first-line treatment in patients with the T315I mutation. It blocks the activity of BCR-Abl by interacting with the myristate-binding site located 23 Å from the ATP-binding site and is the prototype of a type IV inhibitor. Asciminib is a so-called STAMP inhibitor that Specifically Targets the Abl Myristoyl Pocket.
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]Asciminib, the first BCR::ABL1 inhibitor that Specifically Targets the ABL Myristoyl Pocket (STAMP), is approved worldwide for the treatment of adults with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase (CML-CP) treated with ≥2 prior tyrosine kinase inhibitors (TKIs). In ASCEMBL, patients with CML-CP treated with ≥2 prior TKIs were randomized (stratified by baseline major cytogenetic response [MCyR]) 2:1 to asciminib 40 mg twice daily or bosutinib 500 mg once daily. Consistent with previously published primary analysis results, after a median follow-up of 2.3 years, asciminib continued to demonstrate superior efficacy and better safety and tolerability than bosutinib. The major molecular response (MMR) rate at week 96 (key secondary endpoint) was 37.6% with asciminib vs 15.8% with bosutinib; the MMR rate difference between the arms, after adjusting for baseline MCyR, was 21.7% (95% CI, 10.53-32.95; two-sided p = 0.001). Fewer grade ≥3 adverse events (AEs) (56.4% vs 68.4%) and AEs leading to treatment discontinuation (7.7% vs 26.3%) occurred with asciminib than with bosutinib. A higher proportion of patients on asciminib than bosutinib remained on treatment and continued to derive benefit over time, supporting asciminib as a standard of care for patients with CML-CP previously treated with ≥2 TKIs.
[Pharmacological and clinical profile of asciminib hydrochloride, a novel first-in-class tyrosine kinase inhibitor specifically targeting ABL myristoyl pocket]. [2023]On March 28th, 2022, asciminib hydrochloride (Scemblix® Tablets 20 ‍mg/40 ‍mg), the world's first tyrosine kinase inhibitor (TKI) specifically targeting the ABL myristoyl pocket (STAMP inhibitor), was approved for chronic myeloid leukemia (CML) resistant or intolerant to prior therapy. Asciminib specifically binds to the myristoyl pocket, an allosteric site of BCR::ABL1, and inhibits the ABL1 family molecules. In vitro and in vivo pharmacology studies demonstrated cell growth inhibition and antitumor effects of asciminib. The international phase I study for patients with chronic or accelerated phase CML investigated the maximum tolerated dose (MTD) and recommended dose for expansion (RDE) of asciminib monotherapy. However, the MTD was not reached, so and RDE was determined based on tolerability, safety, pharmacokinetics (PK) and preliminary efficacy data obtained by the time of the study. RDE was determined to be 40 ‍mg twice daily in chronic or accelerated phase CML without T315I mutation, and 200 ‍mg twice daily in chronic or accelerated phase CML with T315I mutation. The international phase III study for patients with chronic phase CML who were previously treated with ≥2 TKIs and resistant or intolerant to the recent treatment demonstrated the superiority of asciminib over bosutinib in achieving the primary endpoint of a major molecular response (MMR) at week 24. Regarding safety, the most common treatment-related adverse event in asciminib arm was thrombocytopenia, and others included neutropenia. Asciminib is expected to be a new treatment option for CML patients who have limited choices due to resistance or intolerance to previous therapies.
A phase 3, open-label, randomized study of asciminib, a STAMP inhibitor, vs bosutinib in CML after 2 or more prior TKIs. [2023]Patients with chronic myeloid leukemia in chronic phase (CML-CP) resistant/intolerant to ≥2 tyrosine kinase inhibitors (TKIs) are at high risk of experiencing poor outcomes because of disease biology and inadequate efficacy and/or safety of current therapies. Asciminib, a first-in-class BCR-ABL1 inhibitor Specifically Targeting the ABL Myristoyl Pocket (STAMP), has the potential to overcome resistance/intolerance to approved TKIs. In this phase 3, open-label study, patients with CML-CP previously treated with ≥2 TKIs were randomized (2:1) to receive asciminib 40 mg twice daily vs bosutinib 500 mg once daily. Randomization was stratified by major cytogenetic response (MCyR) status at baseline. The primary objective was to compare the major molecular response (MMR) rate at week 24 for asciminib vs bosutinib. A total of 233 patients were randomized to asciminib (n = 157) or bosutinib (n = 76). Median follow-up was 14.9 months. The MMR rate at week 24 was 25.5% with asciminib and 13.2% with bosutinib. The difference in MMR rate between treatment arms, after adjusting for MCyR at baseline, was 12.2% (95% confidence interval, 2.19-22.30; 2-sided P = .029). Fewer grade ≥3 adverse events (50.6% vs 60.5%) and adverse events leading to treatment discontinuation (5.8% vs 21.1%) occurred with asciminib than with bosutinib. The study showed a superior efficacy of asciminib compared with that of bosutinib, together with a favorable safety profile. These results support the use of asciminib as a new therapy in patients with CML-CP who are resistant/intolerant to ≥2 prior TKIs. This trial was registered at www.clinicaltrials.gov as #NCT03106779.
Asciminib vs bosutinib in CML patients pretreated with ≥2 tyrosine kinase inhibitors: Results from the Japanese subgroup analysis of ASCEMBL study. [2023]Asciminib, a first-in-class, allosteric inhibitor of BCR-ABL1 that acts by STAMP (Specifically Targeting the ABL Myristoyl Pocket), is a novel therapeutic option for patients with chronic myeloid leukemia (CML). In the global, phase 3, open-label ASCEMBL study in patients with CML in chronic phase (CML-CP) pretreated with ≥2 tyrosine kinase inhibitors (TKIs) (NCT03106779), asciminib (40 mg twice-daily) demonstrated significant superiority over the ATP-competitive TKI bosutinib (500 mg once daily) for the primary endpoint of major molecular response (MMR; BCR::ABL1 transcript levels on the international scale [BCR::ABL1IS ] ≤0.1%) at week 24. Here, we report results from a descriptive subgroup analysis of Japanese patients enrolled in ASCEMBL study (data cut-off: May 25, 2020). Overall, 16 Japanese patients were randomized (asciminib, n = 13; bosutinib, n = 3). At week 24, the MMR rate with asciminib was 30.8% (4/13; 95% confidence interval [CI], 9.09-61.43). BCR::ABL1IS ≤1% and complete cytogenic response (CCyR) at week 24 were 61.5% (8/13 patients) and 50.0% (4/8 patients), respectively. In the bosutinib group, no patient achieved MMR, CCyR, or BCR::ABL1IS ≤1%, but results were limited by the low number of patients. The safety profile of asciminib was comparable to that previously observed in the overall study population. Findings from this Japanese subgroup analysis of the ASCEMBL study support the use of asciminib for the treatment of Japanese patients with CML-CP previously treated with ≥2 TKIs. ClinicalTrials.gov Identifier: NCT03106779.
Asciminib: the first-in-class allosteric inhibitor of BCR::ABL1 kinase. [2023]The prognosis of patients with chronic phase (CP) chronic myeloid leukemia (CML) has significantly improved due to the development of potent BCR::ABL1 tyrosine kinase inhibitors (TKIs). However, approximately 15‒20% of patients ultimately experience treatment failure due to resistance or intolerance to TKI therapy. As the prognosis of patients in whom multiple TKIs fail remains poor, an optimal therapeutic approach is required to treat the condition. Asciminib, an allosteric inhibitor that targets ABL1 myristoyl pocket, has been approved by the Food and Drug Administration for use in patients with CP-CML resistant or intolerant to ≥2 prior TKIs or those with T315I mutation. In a phase 1 trial, asciminib monotherapy showed a relatively favorable safety profile and potent efficacy in patients with and without the T315I mutation. In a subsequent phase 3 trial, asciminib treatment was associated with a significantly higher major molecular response rate and lower discontinuation rate than bosutinib in patients with CP-CML for whom two previous TKIs failed. Several clinical trials are being performed in various clinical settings to evaluate the role of asciminib as a frontline treatment for newly diagnosed CP-CML, either as a single agent or in combination with other TKIs as a second-line or additive treatment to improve treatment-free or deep remission. This review summarizes the incidence, available therapies, and outcomes of patients with CP-CML who experienced treatment failure, the mechanism of action, preclinical and clinical data, and ongoing trials for asciminib.