Systemic Treatments There is currently one FDA-approved systemic treatment for metastatic uveal melanoma (UM): tebentafusp (Kimmtrak). Approved in January 2022, tebentafusp is indicated for adult patients with unresectable or metastatic UM who are HLA-A*02:01 positive and remains the only approved systemic therapy as of 2026. Tebentafusp is a targeted immunotherapy that engages T cells to recognize and attack melanoma cells. Some clinicians may also recommend therapies approved for cutaneous melanoma, although their effectiveness in UM is more limited. For patients who are HLA-A*02:01 negative, and whenever appropriate, participation in clinical trials is strongly encouraged, as trials may offer access to investigational systemic therapies before approval.
Targeted Therapy A form of treatment in which drugs are developed to target specific mutations in the tumor with the goal of destroying cancer cells while leaving normal cells intact. These drugs are designed to interfere with the specific molecules, genetic mutations in the tumor itself, that are driving the growth and spread of the tumor. Common genetic mutations in melanoma (such as BRAF) are not often found in UM. The most common mutations in uveal melanoma are the GNAQ, GNA11 and BAP1 genes. Clinical trials are currently underway to develop drugs to target these mutations. Chemotherapy Overall, chemotherapy has not been shown to be effective for uveal melanoma and is rarely used. 16
Immunotherapy A type of systemic treatment given to activate a person’s immune system so that it will destroy melanoma cells within the body. Tebentafusp (Kimmtrak) is a type of immunotherapy specifically approved for metastatic UM. Additionally, there are several that are approved for cutaneous melanoma that have some activity in UM. Some of these treatments may include immune checkpoint inhibitors: ipilimumab (Yervoy), nivolumab (Opdivo), pembrolizumab (Keytruda), nivolumab/ relatlimab (Opdualag). Clinical trials are currently underway to better understand immunotherapies in UM.
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