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BLEXIMENIB

BLEXIMENIB (also known as JNJ-75276617) is a promising new drug currently being investigated in clinical trials for the treatment of acute leukemia, including Acute Myeloid Leukemia (AML) and Acute Lymphoblastic Leukemia (ALL). This oral medication works as a Menin-KMT2A (MLL1) inhibitor, targeting specific genetic alterations found in certain leukemia patients. Multiple clinical trials are currently exploring BLEXIMENIB’s effectiveness both as a standalone treatment and in combination with other established leukemia therapies such as Venetoclax, Azacitidine, and standard chemotherapy regimens. These trials aim to determine the appropriate dosing, safety profile, and effectiveness of BLEXIMENIB in various patient populations, from newly diagnosed to those with relapsed or refractory disease.

Table of Contents

What is BLEXIMENIB?

BLEXIMENIB (also known as JNJ-75276617) is an investigational medication being studied for the treatment of different types of acute leukemia[1]. It belongs to a new class of drugs called Menin-KMT2A (MLL1) inhibitors. This means it works by blocking the interaction between two proteins (Menin and KMT2A) that can contribute to the development of certain types of leukemia[1].

The drug is currently being evaluated in clinical trials to determine its safety, proper dosing, and effectiveness in treating acute leukemia. These studies are helping researchers understand how well BLEXIMENIB works alone and in combination with other cancer medications[2][3].

How BLEXIMENIB Works

BLEXIMENIB is designed to target specific genetic changes that occur in some types of leukemia. Specifically, it targets cancers with alterations in genes called KMT2A (also known as MLL1), NPM1, NUP98, or NUP214[3].

When these genes are altered, they can cause abnormal blood cell production, leading to leukemia. BLEXIMENIB works by inhibiting (blocking) the interaction between a protein called Menin and the KMT2A (MLL1) protein. This interaction is important for the growth of leukemia cells with these specific genetic alterations[1].

By disrupting this interaction, BLEXIMENIB may help stop the growth of leukemia cells and potentially allow normal blood cells to develop again[3].

Conditions Treated with BLEXIMENIB

BLEXIMENIB is being studied for the treatment of two main types of acute leukemia:

  • Acute Myeloid Leukemia (AML): A type of cancer that affects the blood and bone marrow, characterized by the rapid growth of abnormal white blood cells that build up in the bone marrow and interfere with the production of normal blood cells[1][2][3].
  • Acute Lymphoblastic Leukemia (ALL): A type of cancer in which the bone marrow makes too many immature lymphocytes (a type of white blood cell)[1].

BLEXIMENIB is specifically being studied in patients whose leukemia has specific genetic alterations, particularly in the KMT2A (MLL1) or NPM1 genes, as well as NUP98 or NUP214 alterations[3]. These genetic changes are important because they may predict which patients are more likely to respond to treatment with BLEXIMENIB.

Current Clinical Trials

BLEXIMENIB is currently being evaluated in several clinical trials:

  • Phase 1/2 First-in-Human Study: This study is evaluating BLEXIMENIB in patients with acute leukemia to determine the appropriate dose and assess safety and effectiveness. The study includes a dose escalation part to find the right dose and a dose expansion part to further evaluate the selected dose[1].
  • Phase 1b Combination Study: This study is testing BLEXIMENIB in combination with other AML-directed therapies in patients with specific genetic alterations (KMT2A, NPM1, NUP98, or NUP214). The study includes different patient groups:
    • Patients with relapsed/refractory AML (cancer that has returned or not responded to treatment)
    • Newly diagnosed AML patients who cannot receive intensive chemotherapy
    • Newly diagnosed AML patients who are eligible for intensive chemotherapy[3]
  • Phase 3 Randomized Study: This large-scale study is comparing BLEXIMENIB combined with Venetoclax and Azacitidine versus placebo with Venetoclax and Azacitidine in newly diagnosed AML patients with KMT2A rearrangements or NPM1 mutations who cannot receive intensive chemotherapy[2].

BLEXIMENIB Combination Therapies

BLEXIMENIB is being studied both as a standalone treatment and in combination with other cancer medications. Some of the combinations being investigated include:

  • BLEXIMENIB + Venetoclax (VEN): Venetoclax is a medication that helps promote cancer cell death by blocking a protein called BCL-2[3].
  • BLEXIMENIB + Azacitidine (AZA): Azacitidine is a chemotherapy drug that affects cell growth and is commonly used to treat certain types of leukemia[3].
  • BLEXIMENIB + VEN + AZA: This three-drug combination is being tested in both newly diagnosed patients who cannot receive intensive chemotherapy and in patients with relapsed/refractory disease[2][3].
  • BLEXIMENIB + Intensive Chemotherapy: For patients eligible for intensive treatment, BLEXIMENIB is being combined with standard intensive chemotherapy drugs like cytarabine plus daunorubicin or idarubicin[3].

How BLEXIMENIB is Administered

BLEXIMENIB is taken orally (by mouth)[1][2][3]. This makes it more convenient for patients compared to some cancer treatments that require intravenous administration.

In clinical trials, BLEXIMENIB is typically given in 28-day treatment cycles. The exact dosing schedule depends on the specific trial and whether BLEXIMENIB is being given alone or in combination with other medications[2].

When given in combination with other drugs like Venetoclax and Azacitidine, the administration schedule is coordinated to optimize effectiveness while minimizing side effects[2][3].

Safety Profile and Side Effects

As BLEXIMENIB is still in clinical trials, complete information about all possible side effects is not yet available. However, the clinical trials are carefully monitoring patients for any adverse events (side effects)[1][2][3].

The trials are tracking several safety measures, including:

  • Adverse Events (AEs): Any undesirable medical occurrence in a patient receiving BLEXIMENIB, whether or not it’s related to the drug[1].
  • Severity of Side Effects: Side effects are graded from mild (Grade 1) to severe (Grade 5, which means death related to the side effect). This standardized grading system helps researchers understand how serious the side effects are[1][2].
  • Dose-Limiting Toxicities (DLTs): These are side effects severe enough that they prevent further dose increases. Identifying DLTs helps determine the maximum safe dose[1][3].
  • Laboratory Abnormalities: Changes in blood tests and other laboratory values that might indicate effects on organ function[2].

Effectiveness Measures

The clinical trials are evaluating how well BLEXIMENIB works using several important measures:

  • Complete Remission (CR): This means that leukemia cells are no longer detectable in blood and bone marrow samples (less than 5% of cells are blasts), there are no circulating blasts or extramedullary disease, and blood cell counts have returned to normal levels[2][3].
  • Complete Remission with Partial Hematologic Recovery (CRh): This is similar to CR but with partial recovery of blood cell counts[1][3].
  • Complete Remission with Incomplete Hematologic Recovery (CRi): This is when all CR criteria are met except for complete recovery of neutrophil or platelet counts[3].
  • Overall Response Rate (ORR): The percentage of patients who achieve any kind of response to treatment[1][3].
  • Duration of Response (DOR): How long the response to treatment lasts[1].
  • Measurable Residual Disease (MRD) Negativity: This is a more sensitive measure that looks for any remaining leukemia cells even when standard tests show remission[1][2].
  • Event-Free Survival (EFS): The time from starting treatment until treatment failure, relapse, or death[1][2].
  • Overall Survival (OS): How long patients live after starting treatment[1][2].
  • Transfusion Independence: Whether patients no longer need blood or platelet transfusions during treatment[1][2].

Patient Populations That May Benefit

Based on the clinical trials, BLEXIMENIB may potentially benefit several groups of patients with acute leukemia:

  • Patients with Specific Genetic Alterations: Those whose leukemia has alterations in KMT2A (MLL1), NPM1, NUP98, or NUP214 genes may be most likely to benefit from BLEXIMENIB[2][3].
  • Newly Diagnosed Patients Who Cannot Receive Intensive Chemotherapy: Often older patients (≥75 years) or those with other health conditions that make intensive chemotherapy too risky[2][3].
  • Newly Diagnosed Patients Eligible for Intensive Chemotherapy: Typically younger patients (18 to <75 years) without significant health issues that would prevent intensive treatment[3].
  • Patients with Relapsed or Refractory Leukemia: Those whose disease has returned after treatment or has not responded to previous treatments[3].
  • Adolescent Patients: Some trials are including patients as young as 12 years old with relapsed/refractory AML[3].

BLEXIMENIB represents a promising new approach for treating acute leukemia, especially for patients with specific genetic alterations who may not have responded well to existing treatments. As clinical trials progress, more information will become available about its effectiveness and safety profile[1][2][3].

Study Type Patient Population Treatment Primary Outcomes
Phase 1/2 First-in-Human Study (NCT04811560) Patients with Acute Myeloid Leukemia and Acute Lymphoblastic Leukemia BLEXIMENIB as single agent – Safety and tolerability
– Rate of Complete Remission or Complete Remission with Partial Hematologic Recovery (CR/CRh)
Phase 3 Randomized, Double-Blind, Placebo-Controlled Study (NCT06852222) Newly diagnosed AML patients with KMT2A rearrangements or NPM1 mutations who are ineligible for intensive chemotherapy BLEXIMENIB + Venetoclax + Azacitidine vs. Placebo + Venetoclax + Azacitidine – Percentage of patients achieving Complete Remission (CR)
– Overall Survival (OS)
Phase 1b Combination Study (NCT05453903) Three arms:
A) Relapsed/refractory AML
B) Newly diagnosed chemotherapy-ineligible AML
C) Newly diagnosed chemotherapy-eligible AML
(All with specific genetic alterations)		 – Arm A: BLEXIMENIB + Venetoclax or Azacitidine or both
– Arm B: BLEXIMENIB + Venetoclax + Azacitidine
– Arm C: BLEXIMENIB + cytarabine + daunorubicin/idarubicin		 – Safety and tolerability
– Dose-limiting toxicities
– Adverse events

FAQ

  • What type of cancer is BLEXIMENIB being tested to treat? BLEXIMENIB is being tested to treat acute leukemias, specifically Acute Myeloid Leukemia (AML) and Acute Lymphoblastic Leukemia (ALL). It's being studied in patients with particular genetic alterations, including those with KMT2A rearrangements, NPM1 mutations, and NUP98 or NUP214 alterations.
  • How is BLEXIMENIB administered to patients? BLEXIMENIB is administered orally, meaning patients take it by mouth. This makes it more convenient than treatments requiring intravenous administration or hospital visits for infusions.
  • What other medications is BLEXIMENIB being combined with in clinical trials? In clinical trials, BLEXIMENIB is being tested in combination with several established leukemia treatments, including Venetoclax (VEN), Azacitidine (AZA), and traditional chemotherapy agents like cytarabine and daunorubicin or idarubicin. These combinations are being studied to see if they can improve treatment outcomes compared to current standard therapies.
  • What does 'Complete Remission' mean in the context of these clinical trials? Complete Remission (CR) in these trials is defined as having less than 5% bone marrow blasts (immature blood cells), absence of circulating blasts, no extramedullary disease (leukemia outside the bone marrow), an absolute neutrophil count of at least 1,000 per microliter, and a platelet count of at least 100,000 per microliter. Essentially, it means the cancer has responded to treatment and normal blood cell production has recovered to acceptable levels.
  • Who is eligible to participate in BLEXIMENIB clinical trials? Eligibility varies by specific trial, but generally includes patients with acute leukemia (AML or ALL) who have specific genetic alterations like KMT2A rearrangements or NPM1 mutations. Some trials focus on newly diagnosed patients who either are or aren't eligible for intensive chemotherapy, while others target patients with relapsed or refractory disease (cancer that has returned or didn't respond to previous treatments). Age requirements also vary, with some trials including patients as young as 12 years old, while others are limited to adults 18 and older.

Ongoing Clinical Trials on BLEXIMENIB

  • A study of bleximenib combined with intensive chemotherapy for adults with newly diagnosed acute myeloid leukemia with specific genetic changes.

    Recruiting

    1 1
    Investigated diseases:
    Investigated drugs:
    Austria Belgium Denmark Estonia Finland Germany +8

  • A Study Testing Bleximenib in People with Acute Leukemia

    Recruiting

    1 1
    Investigated drugs:
    Belgium France The Netherlands Spain

  • Study of Bleximenib, Venetoclax, and Azacitidine Treatment for Newly Diagnosed Acute Myeloid Leukemia Patients Ineligible for Intensive Chemotherapy

    Recruiting

    1 1 1
    Investigated drugs:
    Austria Belgium Czechia Denmark France Germany +6

  • Study of Bleximenib with Drug Combination for Patients with Acute Myeloid Leukemia with KMT2A or NPM1 Alterations

    Not recruiting

    1 1 1
    Investigated drugs:
    France Germany Italy Spain

Glossary

  • Acute Myeloid Leukemia (AML): A type of cancer that affects the blood and bone marrow, characterized by the rapid growth of abnormal white blood cells that build up in the bone marrow and interfere with normal blood cell production.
  • Acute Lymphoblastic Leukemia (ALL): A type of cancer that affects the blood and bone marrow, where the body makes too many immature lymphocytes (a type of white blood cell).
  • Menin-KMT2A (MLL1) Inhibitor: A type of drug that blocks the interaction between the proteins Menin and KMT2A (previously known as MLL1), which is important for the growth of certain types of leukemia cells with specific genetic alterations.
  • Recommended Phase 2 Dose (RP2D): The optimal dose of a drug determined from Phase 1 trials that balances effectiveness with acceptable side effects, which is then used in Phase 2 trials.
  • Complete Remission (CR): A treatment response where there are less than 5% blast cells in the bone marrow, no blast cells in the blood, no signs of disease outside the bone marrow, and recovery of normal blood cell counts.
  • Complete Remission with Partial Hematologic Recovery (CRh): Similar to Complete Remission but with partial recovery of blood cell counts (neutrophils >500/microliter and platelets >50,000/microliter).
  • Complete Remission with Incomplete Hematologic Recovery (CRi): When a patient meets all criteria for complete remission except their blood cell counts haven't fully recovered (neutrophils <1,000/microliter or platelets <100,000/microliter).
  • Dose-Limiting Toxicity (DLT): Side effects severe enough to prevent increasing the dose of a drug during clinical trials.
  • Adverse Events (AEs): Any undesirable experience associated with the use of a medical product in a patient. The events are graded from mild (Grade 1) to death (Grade 5).
  • Overall Response Rate (ORR): The percentage of patients whose cancer shrinks or disappears after treatment.
  • Duration of Response (DOR): The length of time from first documented response to a treatment until disease progression or relapse.
  • Event-Free Survival (EFS): The time from start of treatment until treatment failure, disease relapse, or death from any cause.
  • Overall Survival (OS): The time from start of treatment until death from any cause.
  • Measurable Residual Disease (MRD): The small number of cancer cells that may remain after treatment, even when a patient appears to be in remission. These cells can only be detected using very sensitive tests.
  • Transfusion Independence: When a patient no longer needs blood transfusions (red blood cells or platelets) for a defined period, usually 56 days (8 weeks) in these trials.
  • Relapsed/Refractory: Describes cancer that has returned after a period of improvement (relapsed) or that has not responded to previous treatment (refractory).
  • KMT2A Rearrangements: Genetic changes involving the KMT2A gene (also known as MLL1) that are associated with certain types of leukemia.
  • NPM1 Mutations: Changes in the Nucleophosmin 1 gene that are commonly found in patients with AML and can affect how the disease responds to treatment.
  • Allogeneic Hematopoietic Stem Cell Transplant (Allo-HSCT): A procedure where a patient receives blood-forming stem cells from a genetically similar, but not identical, donor to restore the bone marrow's ability to produce healthy blood cells.
  • Venetoclax (VEN): An oral medication that works by blocking BCL-2, a protein that helps cancer cells survive. It's often used in combination with other drugs to treat leukemia.
  • Azacitidine (AZA): A chemotherapy drug that affects the way cancer cells use genetic material (DNA), which may kill cancer cells or stop them from growing. It can be given by injection under the skin or through an intravenous (IV) line.

References

  1. https://clinicaltrials.gov/study/NCT04811560
  2. https://clinicaltrials.gov/study/NCT06852222
  3. https://clinicaltrials.gov/study/NCT05453903