A diagnosis of a rare and aggressive cancer like uveal melanoma, especially once it has spread, can be a deeply frightening and uncertain time. For years, patients with this specific type of eye cancer had very few effective treatment options. However, a breakthrough in cancer research has brought a new wave of hope. This advancement comes in the form of Kimmtrak (tebentafusp-tebn).

Kimmtrak is a first-in-class prescription medication that represents a completely new way of fighting this disease. It is a type of cutting-edge immunotherapy known as a bispecific T-cell engager. It is not chemotherapy or traditional radiation; instead, it is a highly specialized, targeted therapy designed to harness the power of your own immune system to find and destroy cancer cells. For a specific group of patients with metastatic uveal melanoma, Kimmtrak is the first and only therapy that has been shown to help them live longer.

What does Kimmtrak do?

Kimmtrak is approved by the U.S. Food and Drug Administration (FDA) for the treatment of adults with unresectable or metastatic uveal melanoma. This means it is used when the eye cancer cannot be removed with surgery or has spread to other parts of the body.

Importantly, Kimmtrak is not for every patient with this disease. It is a form of precision medicine for individuals who test positive for a specific genetic marker called HLA-A*02:01. This marker is a normal part of the immune system and is present in about half of the general population.

The primary goal of treatment with Kimmtrak is to improve overall survival. In the pivotal clinical trial that led to its approval, patients treated with Kimmtrak had a significantly better chance of living longer compared to patients who received other standard cancer therapies. It was the first therapy ever to show a survival benefit for patients with previously untreated metastatic uveal melanoma (Immunocore, 2022).

How does Kimmtrak work?

The way Kimmtrak works is a brilliant example of modern cancer immunotherapy. To understand it, think of your immune system’s T-cells as highly trained soldiers whose job is to find and eliminate threats like cancer cells. However, cancer cells are masters of disguise and can often hide from these soldiers.

Kimmtrak acts as a special “bridge” or a “matchmaker” that unmasks the cancer cells and forces the T-cells to attack. The Kimmtrak molecule is engineered to be bispecific, meaning it has two different “arms”:

1. One arm is designed to grab onto a specific protein called gp100, which is found on the surface of the uveal melanoma cells.
2. The other arm is designed to grab onto a protein called CD3, which is found on the surface of your T-cells.

By simultaneously binding to both the cancer cell and the T-cell, Kimmtrak physically brings the immune soldier directly to its target. This forced connection activates the T-cell, which then releases powerful toxins that destroy the melanoma cell. This unique mechanism redirects your body’s own immune system to specifically recognize and fight the cancer that it previously could not see.

Kimmtrak side effects

Because Kimmtrak powerfully activates the immune system, its side effects are primarily related to this widespread immune response.

Kimmtrak has a boxed warning, the FDA’s most serious type, for the risk of Cytokine Release Syndrome (CRS). CRS is a potentially serious and life-threatening condition that can occur when the immune system becomes over-activated. Symptoms can include fever, low blood pressure (hypotension), a low level of oxygen in the blood (hypoxia), chills, nausea, vomiting, fatigue, headache, and confusion.

The most common side effects of Kimmtrak include:

• Cytokine Release Syndrome
• Skin rash, itching, and redness
• Fever
• Nausea and vomiting
• Abdominal pain
• Fatigue
• Swelling (edema)
• Headache
• A drop in blood pressure

Initial treatment requires hospitalization for close monitoring due to CRS risk. Contact your doctor immediately for severe blistering or peeling skin rash. Your doctor will closely monitor all side effects, especially early in treatment.

Kimmtrak dosage

Kimmtrak is not a pill. It is administered as an intravenous (IV) infusion into a vein. The infusion itself usually takes about 15 to 20 minutes and is given once a week.

Due to high CRS risk, initial doses require strict safety monitoring. The first three infusions are hospital-administered, each followed by a mandatory 16-hour hospital stay for observation of vital signs, oxygen, and CRS. If severe side effects are absent after the third dose, weekly outpatient infusions may be possible. Regular blood tests, including liver function, will be ordered throughout treatment.

Does Kimmtrak have a generic version?

No, Kimmtrak (tebentafusp-tebn) is a highly complex, brand-name biologic medication. There is no generic or biosimilar version available. However, international versions may exist in other markets. As a first-in-class therapy, it is protected by patents that prevent other manufacturers from creating an equivalent for many years.

Conclusion

For patients with HLA-A*02:01-positive metastatic uveal melanoma, Kimmtrak represents a landmark achievement and a new standard of care. Its innovative approach of using the body’s own immune system to fight cancer has, for the first time, provided a proven survival benefit for this challenging disease.

While the treatment comes with the serious risk of Cytokine Release Syndrome and requires intensive monitoring in a hospital setting at the start, its potential benefits are profound. A thorough discussion with your oncology team will help you understand the risks and benefits. When administered under the care of an experienced medical team, Kimmtrak offers a powerful and hopeful path forward.

References

1. Immunocore. (2022). KIMMTRAK® (tebentafusp-tebn) Prescribing Information. U.S. Food and Drug Administration. Retrieved from https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/761226s000lbl.pdf
2. National Cancer Institute. (2022). FDA Approves Tebentafusp for Unresectable or Metastatic Uveal Melanoma. Retrieved from https://www.cancer.gov/news-events/cancer-currents-blog/2022/fda-tebentafusp-uveal-melanoma
3. Mayo Clinic. (2024). Tebentafusp-tebn (Intravenous Route). Retrieved from https://www.mayoclinic.org/drugs-supplements/tebentafusp-tebn-intravenous-route/side-effects/drg-20524419