Blinatumomab + Asciminib for Philadelphia Chromosome Positive Leukemia
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: M.D. Anderson Cancer Center
No Placebo Group
Prior Safety Data
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?To learn if the combination of blinatumomab and asciminib can help to control Ph+ ALL.
What data supports the effectiveness of the drug Asciminib for Philadelphia Chromosome Positive Leukemia?
Asciminib has shown effectiveness in treating chronic myeloid leukemia (CML) in patients who have not responded to at least two other treatments, with better results and fewer side effects compared to another drug, bosutinib. It is particularly effective for patients with specific mutations that make other treatments less effective.
12345Will I have to stop taking my current medications?
The trial protocol does not specify whether you need to stop taking your current medications. However, if you have taken investigational antileukemic or chemotherapy agents in the last 7 days, you may need to wait until you recover from any side effects before joining the study.
How is the drug combination of Blinatumomab and Asciminib unique for treating Philadelphia Chromosome Positive Leukemia?
This drug combination is unique because Asciminib is a novel type of drug that specifically targets a unique part of the BCR-ABL1 protein, which is often resistant to other treatments, while Blinatumomab helps the immune system attack cancer cells. Asciminib's ability to target the myristoyl pocket of the BCR-ABL1 protein makes it effective against mutations that other drugs can't treat.
13458Is the combination of Blinatumomab and Asciminib safe for humans?
Asciminib has been studied in patients with chronic myeloid leukemia and has shown a generally favorable safety profile. Common side effects include increased pancreatic enzymes, low platelet counts, high blood pressure, and low white blood cell counts. Most side effects occurred in the first year of treatment, and the likelihood of new side effects decreased over time.
45678Eligibility Criteria
This trial is for patients with a type of leukemia known as Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia (Ph+ ALL). Specific eligibility criteria are not provided, but typically participants would need to meet certain health standards and may be required to have tried other treatments first.Participant Groups
The study is testing the effectiveness of combining two drugs, Blinatumomab and Asciminib, in treating Ph+ ALL. It's a Phase II trial, which means it focuses on the treatment's efficacy and side effects in a larger group than initial trials.
1Treatment groups
Experimental Treatment
Group I: Blinatumomab + AsciminibExperimental Treatment2 Interventions
Participants found to be eligible to take part in this study will receive 5 cycles of blinatumomab and asciminib, followed by asciminib alone for as long as it benefits the participant.
Participants will receive blinatumomab as a continuous (non-stop) infusion on Days 4-31 of Cycle 1 and on Days 1-28 of Cycles 2-5.
Participants will take asciminib by mouth 2 times every day during this study.
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:
MD Anderson Cancer CenterHouston, TX
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Who is running the clinical trial?
M.D. Anderson Cancer CenterLead Sponsor
Novartis PharmaceuticalsIndustry Sponsor
References
Asciminib: First Approval. [2022]Asciminib (Scemblix®) is an orally administered, small molecule, selective allosteric inhibitor that targets the myristoyl pocket of the BCR-ABL1 tyrosine kinase and is being developed by Novartis for the treatment of haematological malignancies, including Philadelphia chromosome-positive (Ph+) chronic myeloid leukaemia (CML). The drug is active against a number of the single catalytic-site mutations, such as T315I, that confer resistance to conventional tyrosine kinase inhibitors (TKIs) that bind to the ATP-binding site of BCR-ABL1. In October 2021, asciminib monotherapy was granted accelerated approval for the treatment of adults with Ph+ CML in chronic phase (CML-CP), previously treated with ≥ 2 TKIs, and full approval for the treatment of adults with Ph+ CML-CP with the T315I mutation. The drug is under regulatory review for use as monotherapy in CML in the EU, and is in phase 1-3 development exploring its potential in first-line, later-line and paediatric patients with CML. This article summarizes the milestones in the development of asciminib leading to this first approval for the treatment of adults with Ph+ CML-CP, previously treated with ≥ 2 TKIs, and Ph+ CML-CP with the T315I mutation.
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.
Asciminib for chronic myeloid leukaemia: Next questions. [2022]Recent approval of asciminib, a novel "specifically targeting the ABL myristoyl pocket" (STAMP) BCR-ABL1 inhibitor, for the treatment of chronic myeloid leukaemia (CML) patients who have either failed ≥2 lines of therapy or have the T315I mutation, has provided clinicians with a wider selection of potentially effective treatment options. Asciminib has the attractive twin attributes of high potency directed against BCR-ABL1 and good tolerability based on its limited off-target effects. However, it is unclear exactly where asciminib will be positioned amongst the other available tyrosine kinase inhibitors (TKIs), especially ponatinib which is also available for the same indications. There are many questions yet to be answered with regard to the optimal use of asciminib which include its role in the first- and second-line settings, combination therapy with other TKIs, and effectiveness in advanced phase CML. In this review, we discuss the available data on asciminib while exploring a number of clinical trials in progress. Finally, we provide our opinion based on the current data about where asciminib is most likely to be the optimal choice, which will hopefully assist clinicians with therapy selection.
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).
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.
Asciminib monotherapy in patients with CML-CP without BCR::ABL1 T315I mutations treated with at least two prior TKIs: 4-year phase 1 safety and efficacy results. [2023]Asciminib is approved for patients with Philadelphia chromosome-positive chronic-phase chronic myeloid leukemia (CML-CP) who received ≥2 prior tyrosine kinase inhibitors or have the T315I mutation. We report updated results of a phase 1, open-label, nonrandomized trial (NCT02081378) assessing the safety, tolerability, and antileukemic activity of asciminib monotherapy 10-200 mg once or twice daily in 115 patients with CML-CP without T315I (data cutoff: January 6, 2021). After ≈4-year median exposure, 69.6% of patients remained on asciminib. The most common grade ≥3 adverse events (AEs) included increased pancreatic enzymes (22.6%), thrombocytopenia (13.9%), hypertension (13.0%), and neutropenia (12.2%); all-grade AEs (mostly grade 1/2) included musculoskeletal pain (59.1%), upper respiratory tract infection (41.7%), and fatigue (40.9%). Clinical pancreatitis and arterial occlusive events (AOEs) occurred in 7.0% and 8.7%, respectively. Most AEs occurred during year 1; the subsequent likelihood of new events, including AOEs, was low. By data cutoff, among patients without the indicated response at baseline, 61.3% achieved BCR::ABL1 ≤ 1%, 61.6% achieved ≤0.1% (major molecular response [MMR]), and 33.7% achieved ≤0.01% on the International Scale. MMR was maintained in 48/53 patients who achieved it and 19/20 who were in MMR at screening, supporting the long-term safety and efficacy of asciminib in this population.
[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.
The EMA Assessment of Asciminib for the Treatment of Adult Patients With Philadelphia Chromosome-Positive Chronic Myeloid Leukemia in Chronic Phase Who Were Previously Treated With at Least Two Tyrosine Kinase Inhibitors. [2023]Asciminib is an allosteric high-affinity tyrosine kinase inhibitor (TKI) of the BCR-ABL1 protein kinase. This kinase is translated from the Philadelphia chromosome in chronic myeloid leukemia (CML). Marketing authorization for asciminib was granted on August 25, 2022 by the European Commission. The approved indication was for patients with Philadelphia chromosome-positive CML in the chronic phase which have previously been treated with at least 2 TKIs. Clinical efficacy and safety of asciminib were evaluated in the open-label, randomized, phase III ASCEMBL study. The primary endpoint of this trial was major molecular response (MMR) rate at 24 weeks. A significant difference in MRR rate was shown between the asciminib treated population and the bosutinib control group (25.5% vs. 13.2%, respectively, P = .029). In the asciminib cohort, adverse reactions of at least grade 3 with an incidence ≥ 5% were thrombocytopenia, neutropenia, increased pancreatic enzymes, hypertension, and anemia. The aim of this article is to summarize the scientific review of the application which led to the positive opinion by the European Medicines Agency's Committee for Medicinal Products for Human Use.