HonorHealth Launches First Global Trial of Novel T Cell Therapy Targeting Aggressive Melanoma

• HonorHealth Research Institute has treated the first patient in a 50-site international Phase III clinical trial testing IMA203 TCR-T, the world's first T cell receptor therapy targeting PRAME in melanoma.
• The innovative ACTengine® therapy, developed by Immatics, engineers a patient's own T cells to target PRAME peptides commonly found in melanoma tumors, requiring only a single dose with a two-week manufacturing turnaround.
• Previous Phase I results published in Nature Medicine showed a 54% response rate with median response duration exceeding one year, offering new hope for patients with advanced melanoma who have exhausted other treatment options.

HonorHealth Research Institute has initiated a groundbreaking international clinical trial by treating the first patient in a study that will evaluate a novel cellular therapy targeting aggressive melanoma. The trial spans 50 sites globally and focuses on a new therapeutic approach for patients with difficult-to-treat melanoma, particularly those whose cancer has metastasized.

The innovative therapy targets PRAME (PReferentially expressed Antigen in MElanoma), a peptide commonly found in melanoma tumors. This approach harnesses the patient's own immune system by extracting T cells, enhancing them in the laboratory, and multiplying them into billions of cancer-fighting cells before reinfusing them back into the patient.

"We are excited about the potential of this new type of cellular therapy," said Justin Moser, M.D., an associate clinical investigator in the Research Institute's Cancer Research Division and associate research professor at Arizona State University's School of Medicine and Advanced Medical Engineering.

The SUPRAME Clinical Trial

The Phase III trial, named SUPRAME, will enroll approximately 360 patients to test an engineered T cell receptor (TCR) therapy called ACTengine® IMA203 TCR-T, developed by Immatics, a clinical-stage biotechnology company based in Houston, Texas. This represents the world's first TCR therapeutic specifically targeting PRAME.

The treatment process involves several key steps:

1. T cells are extracted from the patient's blood
2. These cells are genetically re-engineered to recognize and target cancer cells expressing PRAME
3. The modified cells are multiplied by billions in the laboratory
4. The enhanced T cells are then infused back into the patient as a single dose

A notable advantage of this therapy is its relatively quick manufacturing turnaround time of approximately two weeks, which is faster than some other cellular therapies currently available.

Promising Early Results

The decision to advance to a Phase III trial follows encouraging results from a Phase I study that demonstrated both safety and efficacy with minimal side effects. These initial findings were published in Nature Medicine on April 9.

According to the published research, "Autologous T cell therapy for PRAME+ advanced solid tumors in HLA-A*02+ patients: a phase 1 trial," the early phase clinical trial showed:

• A response rate of 54%
• Median duration of response exceeding one year
• A subgroup of 12 out of 26 patients experienced more than 50% reduction in tumor lesions
• Median progression-free survival of 13.4 months in this subgroup

These results are particularly significant for patients with advanced melanoma who have exhausted other treatment options.

Hope for Advanced Melanoma Patients

Melanoma is an aggressive form of skin cancer that becomes particularly challenging to treat once it has metastasized to other parts of the body. Traditional treatments include surgery, radiation, immunotherapy, and targeted therapies, but options become limited when the disease progresses or recurs.

"Patients with advanced stage melanoma that has spread to other parts of the body, and who have exhausted other possibilities, might now have new options, giving them and their loved ones renewed hope," Dr. Moser explained.

The Science Behind TCR-T Cell Therapy

Unlike some other immunotherapies, TCR-T cell therapy is designed to recognize cancer-specific proteins inside tumor cells. The engineered T cells can identify and attack cancer cells that present specific peptides (in this case, derived from PRAME) on their surface in association with HLA molecules.

This approach differs from CAR-T cell therapies, which recognize proteins on the cell surface and have been primarily successful in blood cancers. TCR-T therapies like IMA203 have the potential to target a wider range of solid tumors, including melanoma.

Cedrik Britten, Immatics' Chief Medical Officer, expressed gratitude for the collaboration: "We are tremendously grateful for all the dedicated professionals at clinical institutions in the United States and Europe who support us in our mission of delivering the power of T cells to patients with cancer."

As the SUPRAME trial progresses, researchers will continue to evaluate the therapy's efficacy, durability of response, and safety profile in a larger patient population. If successful, this approach could represent a significant advancement in the treatment landscape for advanced melanoma and potentially other PRAME-expressing cancers.