KIMMTRAK (tebentafusp-tebn) is a novel bispecific protein composed of a soluble T cell receptor fused to an anti-CD3 immune-effector function. It specifically targets gp100, a lineage antigen expressed in melanocytes and melanoma. KIMMTRAK is the first molecule developed using Immunocore’s ImmTAC technology platform, designed to redirect and activate T cells to recognize and kill tumor cells. KIMMTRAK has been approved for the treatment of HLA-A*02:01-positive adult patients with unresectable or metastatic uveal melanoma in several regions, including the United States, European Union, Canada, Australia, and the United Kingdom. It has been granted Breakthrough Therapy Designation, Fast Track designation, and orphan drug designation by the FDA, among other regulatory recognitions.
Uveal melanoma is a rare and aggressive form of melanoma that originates in the uveal tract of the eye, which includes the iris, ciliary body, and choroid. It is the most common primary intraocular malignancy in adults, but still relatively rare, with approximately 2,500 new cases diagnosed annually in the United States. Uveal melanoma can be challenging to detect early due to its location within the eye and may not present noticeable symptoms until it has progressed. When symptoms do occur, they can include visual disturbances, such as blurred vision or floaters, and changes in the appearance of the eye.
The prognosis for uveal melanoma varies based on factors such as tumor size, location, and genetic markers. Up to 50% of patients with uveal melanoma eventually develop metastatic disease, typically spreading to the liver, which significantly impacts survival rates. Treatment options include radiation therapy, laser therapy, and surgical removal of the tumor or the eye (enucleation) in severe cases. Recent advancements in targeted therapies and immunotherapies, such as KIMMTRAK (tebentafusp-tebn), offer new hope for improving outcomes in patients with advanced or metastatic uveal melanoma.
Companion diagnostic testing plays a critical role in determining the suitability of prescribing KIMMTRAK (tebentafusp-tebn) for treating uveal melanoma. Specifically, KIMMTRAK is approved for use in patients with unresectable or metastatic uveal melanoma who are positive for the HLA-A*02:01 allele. This genetic marker is necessary for the effective binding of KIMMTRAK to both the T cells and the melanoma cells, facilitating the immune system’s recognition and destruction of the cancer cells.
The presence of the HLA-A*02:01 allele is identified through genetic testing, ensuring that only patients who have this specific human leukocyte antigen (HLA) variant are treated with KIMMTRAK. This targeted approach maximizes the efficacy of the treatment and avoids unnecessary exposure to the drug for patients who are unlikely to benefit from it. By integrating companion diagnostic testing into the treatment decision process, healthcare providers can personalize therapy for uveal melanoma patients, improving outcomes and reducing the risk of adverse effects.
This companion diagnostic was developed by an IVD manufacturer as a kit. This is a valid FDA approved test if utilized by 3rd party diagnostic labs who have validated the test using the kit on the specified platform. It is not directly orderable from the manufacturer.
KIMMTRAK (tebentafusp-tebn) is a bispecific T-cell engager that targets gp100, a protein found on melanoma cells, and connects it with CD3 on T-cells. This mechanism helps direct and activate the body’s T-cells to recognize and kill the melanoma cells. It is specifically approved for treating HLA-A*02:01-positive adults with unresectable or metastatic uveal melanoma.
Patients eligible for KIMMTRAK treatment are those with unresectable or metastatic uveal melanoma who are HLA-A*02:01 positive. This HLA type is determined through a companion diagnostic test, ensuring that the therapy is administered to patients who are most likely to benefit from it.
Common side effects of KIMMTRAK include cytokine release syndrome, rash, fever, fatigue, nausea, chills, abdominal pain, edema, hypotension, dry skin, headache, and vomiting. Patients should discuss potential side effects with their healthcare provider to understand the risks and how to manage them.
KIMMTRAK is administered as an intravenous (IV) infusion. The recommended dosing schedule starts with 20 mcg on day 1, followed by 30 mcg on day 8, and 68 mcg on day 15, continuing weekly with 68 mcg as tolerated. The treatment continues until disease progression or unacceptable toxicity occurs.
Companion diagnostic tests are essential for identifying patients who can benefit from KIMMTRAK. These tests determine if a patient’s tumor cells express the HLA-A*02:01 allele. Only patients who test positive for this allele are eligible for KIMMTRAK, ensuring the therapy is appropriately targeted.
Clinical trials have shown that KIMMTRAK significantly improves overall survival in patients with metastatic uveal melanoma compared to other treatments. In a phase 3 trial, patients treated with KIMMTRAK had a median overall survival of 21.7 months, compared to 16 months for those receiving the investigator’s choice of therapy. This demonstrates a meaningful survival benefit for patients with this aggressive cancer.
Immunocore is a commercial-stage biotechnology company pioneering the development of a novel class of TCR bispecific immunotherapies called ImmTAX – Immune mobilizing monoclonal TCRs Against X disease – designed to treat a broad range of diseases, including cancer, autoimmune, and infectious disease. Leveraging its proprietary, flexible, off-the-shelf ImmTAX platform, Immunocore is developing a deep pipeline in multiple therapeutic areas, including nine active clinical and pre-clinical programs in oncology, infectious diseases, and autoimmune diseases. The Company’s most advanced oncology TCR therapeutic, KIMMTRAK has been approved for the treatment of HLA-A*02:01-positive adult patients with unresectable or metastatic uveal melanoma in the United States, European Union, Canada, Australia, and the United Kingdom.