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Autologous T Cells Expressing Cd8A And A T-Cell Receptor Targeting Mage-A4

This article discusses the ongoing clinical trials investigating the use of ADP-A2M4CD8, a genetically modified autologous T-cell therapy, in treating recurrent ovarian cancer. The SURPASS-3 study aims to evaluate the effectiveness and safety of ADP-A2M4CD8 both as a monotherapy and in combination with nivolumab, an immunotherapy drug. This innovative approach targets MAGE-A4 positive tumors in HLA-A*02 positive patients, offering a potential new treatment option for those with limited alternatives.

Table of Contents

What is ADP-A2M4CD8?

ADP-A2M4CD8 is an innovative treatment being studied for recurrent ovarian cancer. It is classified as a type of cell therapy, specifically an autologous T cell therapy. “Autologous” means that the treatment uses the patient’s own cells, which are modified to fight cancer[1].

The full name of this treatment is “Autologous T Cells Expressing CD8A and a T-Cell Receptor Targeting MAGE-A4.” This long name describes how the therapy works:

  • Autologous T Cells: These are immune cells taken from the patient’s own body.
  • CD8A: This is a protein that helps T cells recognize and attack cancer cells.
  • T-Cell Receptor Targeting MAGE-A4: The T cells are genetically modified to recognize a specific protein called MAGE-A4, which is found on some cancer cells.

How Does ADP-A2M4CD8 Work?

ADP-A2M4CD8 works by enhancing the body’s natural immune response against cancer. Here’s a simplified explanation of the process:

  1. T cells are collected from the patient’s blood.
  2. These cells are genetically modified in a laboratory to express CD8A and a receptor that targets MAGE-A4.
  3. The modified cells are then multiplied to create a large number of cancer-fighting cells.
  4. These cells are infused back into the patient’s body.
  5. The modified T cells can now recognize and attack cancer cells that express the MAGE-A4 protein.

This approach is a form of immunotherapy, which harnesses the power of the patient’s own immune system to fight cancer[1].

Target Patient Group

ADP-A2M4CD8 is being studied specifically for patients with:

  • Recurrent ovarian cancer: This means ovarian cancer that has come back after initial treatment.
  • MAGE-A4 positive tumors: The cancer cells must express the MAGE-A4 protein for this treatment to be effective.
  • HLA-A2 positive: Patients must have a specific genetic marker called HLA-A2 for this treatment to work[1].

Clinical Trial Details

A clinical trial called SURPASS-3 (also known as GOG-3084) is currently studying ADP-A2M4CD8. This is a Phase 2 trial, which means it’s testing how well the treatment works and continues to monitor its safety. The trial has two main parts:

  1. ADP-A2M4CD8 Monotherapy: Some patients will receive ADP-A2M4CD8 on its own.
  2. ADP-A2M4CD8 in combination with Nivolumab: Other patients will receive ADP-A2M4CD8 along with another immunotherapy drug called Nivolumab[1].

Eligibility Criteria

To participate in this clinical trial, patients must meet certain criteria. Some key requirements include:

  • Age between 18 and 75 years
  • Confirmed diagnosis of recurrent high-grade serous or high-grade endometrioid ovarian carcinoma
  • Previous treatment with platinum-based chemotherapy
  • Positive for HLA-A2 and MAGE-A4 expression in tumor cells
  • Adequate overall health status

There are also several exclusion criteria, such as certain autoimmune conditions or other cancers[1].

Potential Benefits and Risks

As with any experimental treatment, there are potential benefits and risks:

Potential Benefits:

  • Improved anti-tumor activity against recurrent ovarian cancer
  • A new treatment option for patients who have not responded to other therapies

Potential Risks:

  • Side effects from the treatment itself
  • Risks associated with the lymphodepletion process (a preparatory treatment)
  • Potential for severe immune reactions

The clinical trial is carefully monitoring for any adverse events or side effects[1].

Administration and Dosage

ADP-A2M4CD8 is administered as an intravenous infusion, which means it’s given directly into the bloodstream. The maximum dose being studied is 10 billion cells, given as a single infusion[1].

Before receiving the treatment, patients undergo a process called lymphodepletion, which helps prepare the body to receive the modified T cells.

It’s important to note that this treatment is still experimental and is only available through clinical trials. Patients interested in this therapy should discuss it with their oncologist to determine if they might be eligible for the trial.

Aspect Details
Study Type Phase 2, open-label, randomized, non-comparative clinical trial
Treatment Arms 1. ADP-A2M4CD8 Monotherapy
2. ADP-A2M4CD8 in combination with Nivolumab
Primary Endpoint Objective Response (OR) defined as complete response (CR) or partial response (PR)
Key Eligibility Criteria – Recurrent ovarian cancer positive for MAGE-A4
– HLA-A*02 positive
– Age 18-75 years
– Specific prior therapy requirements
Safety Monitoring – Adverse events (AEs) and serious adverse events (SAEs)
– Replication competent lentivirus (RCL)
– T-cell clonality and insertional oncogenesis
Treatment Administration Intravenous infusion, maximum daily dose of 10 billion organisms

FAQ

  • What is ADP-A2M4CD8? ADP-A2M4CD8 is a type of genetically modified autologous T-cell therapy. It uses a patient's own T-cells that have been engineered to express CD8A and a T-cell receptor targeting MAGE-A4, a protein found in some cancer cells.
  • Who is eligible for this clinical trial? Eligible participants are adults aged 18-75 with recurrent ovarian cancer that is positive for MAGE-A4 and have the HLA-A*02 allele. They must have received prior platinum-based chemotherapy and meet specific disease progression criteria.
  • What is the primary goal of the SURPASS-3 study? The primary goal is to evaluate the anti-tumor activity of ADP-A2M4CD8, both alone and in combination with nivolumab, in patients with MAGE-A4 positive recurrent ovarian cancer.
  • How is the treatment administered? ADP-A2M4CD8 is administered as a solution for infusion intravenously. The maximum daily dose is 10 billion organisms, typically given as a single treatment.
  • What are the main safety considerations for this trial? The trial monitors for adverse events, including serious adverse events and events of special interest. Participants are also checked for replication-competent lentivirus, T-cell clonality, and insertional oncogenesis to ensure safety.

Ongoing Clinical Trials on Autologous T Cells Expressing Cd8A And A T-Cell Receptor Targeting Mage-A4

  • Study on ADP-A2M4CD8 and Nivolumab for Patients with Recurrent Ovarian Cancer

    Not recruiting

    1 1 1
    Investigated diseases:
    Investigated drugs:
    France Spain

Glossary

  • ADP-A2M4CD8: A genetically modified autologous T-cell therapy targeting MAGE-A4 positive tumors in patients with specific HLA types.
  • Autologous: Using cells or tissues obtained from the same individual.
  • MAGE-A4: A protein found in some cancer cells that is targeted by the ADP-A2M4CD8 therapy.
  • HLA-A*02: A specific type of human leukocyte antigen (HLA) that patients must have to be eligible for this trial.
  • Nivolumab: An immunotherapy drug used in combination with ADP-A2M4CD8 in one arm of the trial.
  • Leukapheresis: A procedure to collect white blood cells from a patient's blood.
  • Lymphodepletion: A process to reduce the number of lymphocytes in the body before administering the T-cell therapy.
  • RECIST v1.1: Response Evaluation Criteria in Solid Tumors, a standard way to measure cancer treatment response.
  • Objective Response (OR): The primary endpoint of the trial, defined as either a complete or partial response to treatment.
  • Adverse Events of Special Interest (AESIs): Specific side effects that are closely monitored during the trial due to their potential significance.

References

  1. http://clinicaltrials.eu/trial/study-on-adp-a2m4cd8-and-nivolumab-for-patients-with-recurrent-ovarian-cancer/