What side effects are associated with this type of intervention?

Common treatments for head and neck cancers, particularly those involving immunotherapy and targeted therapies like ADP-A2M4CD8 T-cell therapy, often result in immune-related adverse events (irAEs). These can include pneumonitis, colitis, hepatitis, endocrinopathies, and skin toxicities such as rash and pruritus. Targeted therapies may also cause specific side effects related to the targeted molecules, including hair and skin changes.

What prior FDA approvals exist?

The FDA has approved several immunotherapies for the treatment of Head and Neck Cancers, including pembrolizumab and nivolumab, which are immune checkpoint inhibitors targeting the PD-1 pathway. These drugs have shown efficacy in treating recurrent or metastatic head and neck squamous cell carcinoma (HNSCC). While specific FDA approvals for genetically modified T-cell therapies targeting MAGE-A4 antigen in head and neck cancers are not mentioned, the ongoing research and clinical trials, such as the ADP-A2M4CD8 T-cell therapy, indicate a growing interest in this area.

What other types of research exist?

Promising alternatives to ADP-A2M4CD8 T-cell therapy for head and neck cancer patients include: 1) Pembrolizumab, an immune checkpoint inhibitor targeting PD-1, which has shown efficacy in various cancers including head and neck cancer. 2) Nivolumab, another PD-1 inhibitor, which has demonstrated improved recurrence-free survival in melanoma and is used in head and neck cancers. 3) Combination therapies such as nivolumab with ipilimumab, which have shown potential in treating advanced melanoma and may be applicable to head and neck cancers. 4) Emerging treatments like fecal microbiota transplantation (FMT) to enhance immunotherapy response, and intralesional T-VEC combined with immunotherapy, which have shown promise in early-phase trials for melanoma and could be explored for head and neck cancers.

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CAR T-cell Therapy

ADP-A2M4CD8 + Immunotherapy for Advanced Cancers

Phase 1

Recruiting

Led By David Hong, MD

Research Sponsored by Adaptimmune

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Subject is positive for at least 1 HLA-A*02 inclusion allele

ECOG Performance Status of 0 or 1

Must not have

Clinically significant cardiovascular disease

Active infection with human immunodeficiency virus, hepatitis B virus, hepatitis C virus, or human T cell leukemia virus

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 2.5 years

Awards & highlights

No Placebo-Only Group

Summary

This trial tests a new therapy that uses modified immune cells to fight various cancers in patients with specific markers. The treatment aims to boost the immune system by using trained cells to target and destroy cancer cells.

Who is the study for?

This trial is for adults aged 18-75 with certain cancers (like esophageal, stomach, lung, bladder, melanoma) that are HLA-A2+ and MAGE-A4+. They should have a good performance status and normal heart function. Excluded are those with uncontrolled illnesses, pregnant or breastfeeding women, history of severe allergies to study drugs, active autoimmune diseases, brain metastases or another cancer not in remission.

What is being tested?

The trial tests ADP-A2M4CD8 T-cell therapy alone or combined with nivolumab every four weeks or pembrolizumab every six weeks. It aims to assess the safety and effectiveness of these treatments in patients whose tumors express a specific protein (MAGE-A4) and have a particular human leukocyte antigen (HLA).

What are the potential side effects?

Possible side effects include reactions related to immune system activation such as inflammation in different body parts. There may also be risks associated with infusion reactions from the T-cell therapy or the checkpoint inhibitors nivolumab/pembrolizumab.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I have at least one HLA-A*02 gene variant.

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I am fully active or can carry out light work.

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My tumor tests positive for MAGE-A4.

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My cancer can be measured by scans before specific treatments.

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I am between 18 and 75 years old.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have a serious heart condition.

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I do not have an active infection with HIV, hepatitis B, hepatitis C, or HTLV.

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I do not have cancer spread to the brain or spinal cord that is causing symptoms.

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I do not have any unmanaged ongoing illnesses.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 2.5 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~2.5 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and 2.5 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

To evaluate safety and tolerability of ADP-A2M4CD8 as monotherapy or in combination with either nivolumab or pembrolizumab

To evaluate safety of ADP-A2M4CD8 as monotherapy or in combination with either nivolumab or pembrolizumab

Secondary study objectives

Anti-tumor activity: Best overall response (BOR)

Anti-tumour activity: Overall Response Rate (ORR)

Duration of Response (DOR)

+4 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: Autologous genetically modified ADP-A2M4CD8 cellsExperimental Treatment1 Intervention

0 / 9Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for Head and Neck Cancers (HNC) include immunotherapy approaches such as genetically modified T-cell therapies, immune checkpoint inhibitors, and therapeutic vaccines. ADP-A2M4CD8 T-cell therapy, for instance, involves engineering T-cells to target the MAGE-A4 antigen present on tumor cells, enhancing the immune system's ability to recognize and destroy cancer cells. Immune checkpoint inhibitors, like nivolumab and pembrolizumab, block proteins that prevent T-cells from attacking cancer cells, thereby boosting the immune response. Therapeutic vaccines, such as sipuleucel-T, stimulate the patient's immune system to attack cancer cells. These treatments are crucial for HNC patients as they offer targeted, personalized options that can improve outcomes and reduce the side effects associated with traditional therapies like chemotherapy and radiation.

An update: emerging drugs to treat squamous cell carcinomas of the head and neck.The promise of immunotherapy in head and neck squamous cell carcinoma.Monoclonal antibody MA454 reveals a heterogeneous expression pattern of MAGE-1 antigen in formalin-fixed paraffin embedded lung tumours.