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Human Igg4 Kappa Monoclonal Antibody Against Cd3 And Cd19

This article discusses ongoing clinical trials investigating the use of AZD0486, a human IgG4 kappa monoclonal antibody targeting CD3 and CD19, in patients with relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL). The trials aim to evaluate the safety, tolerability, and effectiveness of this novel treatment approach in adolescents and adults with this challenging form of leukemia.

Table of Contents

What is AZD0486?

AZD0486 is a new medication being studied for the treatment of a specific type of blood cancer. Its scientific name is human IgG4 kappa monoclonal antibody against CD3 and CD19. This means it’s a specially designed protein that can target two specific molecules (CD3 and CD19) found on certain blood cells[1].

The medication is given as a solution for infusion, which means it’s administered directly into the bloodstream through an intravenous (IV) line[1].

Target Condition: B-Cell Acute Lymphoblastic Leukemia

AZD0486 is being studied to treat B-Cell Acute Lymphoblastic Leukemia (B-ALL). This is a type of blood cancer that affects a specific kind of white blood cell called B-lymphocytes. In B-ALL, these cells grow out of control and don’t mature properly, which can crowd out healthy blood cells[1].

The study is specifically looking at patients with relapsed or refractory B-ALL. This means:

  • Relapsed: The cancer has come back after initial treatment
  • Refractory: The cancer hasn’t responded well to previous treatments

How AZD0486 Works

AZD0486 is designed to work in a unique way:

  1. It targets CD19, a molecule found on B-cells (including cancerous B-ALL cells)
  2. It also targets CD3, a molecule found on T-cells (another type of immune cell)
  3. By binding to both, it may help direct the patient’s own T-cells to attack and kill the cancerous B-cells

This approach is known as a bispecific antibody because it targets two different molecules at once[1].

Clinical Trial Overview

AZD0486 is currently being studied in a clinical trial called SYRUS (also known by the number D7405C00001). This is a Phase 1/2 study, which means it’s still in the early stages of testing in humans[1].

The trial is divided into three parts:

  1. Part A (Phase 1a): Dose escalation – finding the right dose
  2. Part B (Phase 1b): Dose optimization – fine-tuning the dose
  3. Part C (Phase 2): Expansion – testing the chosen dose in more patients

Who Can Participate in the Trial?

The trial is looking for patients with specific characteristics, including:

  • Age: 16-80 years old for Part A, 12-80 years old for Parts B and C
  • Diagnosed with CD19+ B-cell Acute Lymphoblastic Leukemia
  • Cancer that has relapsed or is refractory after at least 2 prior therapies (or 1 prior therapy if no standard treatment is available)
  • Relatively good overall health (measured by specific scoring systems)

There are also certain conditions that would prevent someone from participating, such as active cancer in the central nervous system or certain other medical conditions[1].

Trial Objectives

The main goals of this clinical trial are:

  1. To assess if AZD0486 is safe and well-tolerated by patients
  2. To evaluate how effective AZD0486 is in treating relapsed or refractory B-ALL
  3. To understand how the drug moves through and is processed by the body (pharmacokinetics)
  4. To check if patients develop an immune response to the drug (immunogenicity)

Safety and Efficacy Measures

The researchers will be looking at several factors to determine if AZD0486 is safe and effective:

  • Safety: They’ll monitor for any side effects or adverse events
  • Overall Response Rate (ORR): How many patients see their cancer improve or disappear
  • Duration of Response (DoR): How long the improvement lasts
  • Event-free Survival (EFS): How long patients live without their disease getting worse
  • Overall Survival (OS): How long patients live overall
  • Minimal Residual Disease (MRD): Looking for very small amounts of cancer cells that might remain after treatment

Potential Benefits of AZD0486

While it’s important to remember that AZD0486 is still in the testing phase, there are several potential benefits that researchers hope to see:

  • A new treatment option for patients who haven’t responded well to other therapies
  • Possibly more targeted treatment with fewer side effects than traditional chemotherapy
  • Potential to achieve deeper remissions (measured by MRD negativity)
  • May help some patients become eligible for stem cell transplant, which could offer a chance for long-term remission

It’s crucial to note that more research is needed to confirm these potential benefits, and patients should discuss all treatment options with their healthcare team[1].

Aspect Details
Drug Name AZD0486 (Human IgG4 Kappa Monoclonal Antibody Against CD3 and CD19)
Trial Phase Phase 1/2
Condition Relapsed or Refractory B-Cell Acute Lymphoblastic Leukemia (B-ALL)
Age Range 12-80 years (varies by trial part)
Administration Intravenous infusion
Primary Objectives Safety, tolerability, and efficacy assessment
Key Endpoints Dose-limiting toxicities, overall response rate, duration of response, survival measures
Exclusion Criteria Active CNS involvement, isolated extramedullary disease, testicular leukemia, certain prior therapies

FAQ

  • What is AZD0486? AZD0486 is a human IgG4 kappa monoclonal antibody that targets both CD3 and CD19 proteins. It is being studied as a potential treatment for relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL).
  • Who is eligible to participate in these clinical trials? The trials include patients aged 12 to 80 years old with CD19+ B-cell Acute Lymphoblastic Leukemia who have relapsed or become refractory after previous treatments. Specific age ranges and other criteria may vary depending on the trial phase.
  • What are the main objectives of these clinical trials? The main objectives are to assess the safety and tolerability of AZD0486 in participants with relapsed or refractory B-ALL, and to evaluate its efficacy in treating the disease.
  • How is AZD0486 administered to patients? AZD0486 is administered as a solution for infusion, which means it is given intravenously (directly into the bloodstream).
  • What are some of the key outcomes being measured in these trials? Key outcomes include the frequency of dose-limiting toxicities, overall response rate, duration of response, complete remission rate, event-free survival, overall survival, and the ability to proceed to subsequent allogeneic stem cell transplantation.

Ongoing Clinical Trials on Human Igg4 Kappa Monoclonal Antibody Against Cd3 And Cd19

  • A study comparing AZD0486 after reduced chemotherapy versus standard chemotherapy in older or unfit patients with newly diagnosed large B-cell lymphoma

    Recruiting

    3 1 1 1
    Investigated diseases:
    Investigated drugs:
    Belgium Poland

  • Study on the Safety and Effectiveness of AZD0486 Alone or with Other Drugs for Adults with Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, Mantle Cell Lymphoma, or Large B-Cell Lymphoma

    Recruiting

    1 1 1 1
    Investigated diseases:
    Investigated drugs:
    Czechia Denmark France Germany Spain

  • Study on the Effectiveness and Safety of AZD0486 for Adults with Relapsed or Refractory Non-Hodgkin Lymphoma

    Recruiting

    2 1 1
    Investigated diseases:
    Investigated drugs:
    Denmark France Germany Italy Spain Sweden

  • Study on the Safety and Effectiveness of AZD0486 and Tocilizumab for Adolescents and Adults with Relapsed or Refractory B-Cell Acute Lymphoblastic Leukemia

    Not yet recruiting

    1 1 1 1
    Investigated diseases:
    Investigated drugs:
    France Germany Italy Spain

Glossary

  • B-cell Acute Lymphoblastic Leukemia (B-ALL): A type of cancer that affects B-lymphocytes, a kind of white blood cell. It is characterized by the rapid growth of abnormal lymphoblasts in the bone marrow.
  • Monoclonal Antibody: A type of protein made in the laboratory that can bind to substances in the body, including cancer cells. They are used to treat some types of cancer.
  • CD3 and CD19: Proteins found on the surface of certain immune cells. CD3 is present on T-cells, while CD19 is found on B-cells. These are targets for the AZD0486 antibody.
  • Relapsed: The return of a disease or the signs and symptoms of a disease after a period of improvement.
  • Refractory: A condition that does not respond to treatment or stops responding after initial improvement.
  • Dose-Limiting Toxicity (DLT): Side effects of a drug that are severe enough to prevent an increase in dose or require a decrease in dose.
  • Overall Response Rate (ORR): The proportion of patients whose cancer shrinks or disappears after treatment.
  • Complete Remission (CR): The disappearance of all signs of cancer in response to treatment.
  • Minimal Residual Disease (MRD): Small numbers of cancer cells that remain in the body during or after treatment.
  • Allogeneic Stem Cell Transplantation (alloSCT): A procedure in which a person receives blood-forming stem cells from a genetically similar, but not identical, donor.

References

  1. http://clinicaltrials.eu/trial/study-on-the-safety-and-effectiveness-of-azd0486-and-tocilizumab-for-adolescents-and-adults-with-relapsed-or-refractory-b-cell-acute-lymphoblastic-leukemia/