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The FDA approved the first treatment for unresectable or metastatic uveal melanoma.

Tebentafusp-tebn (Kimmtrak), a bispecific T-cell engager, is the first approved T-cell receptor therapy. The drug consists of a soluble T-cell receptor fused to an anti-CD3 immune effector. The drug came from a development platform designed to treat a variety of diseases, including autoimmune and infectious diseases, in addition to cancer.

"Uveal melanoma is a devastating disease that has historically resulted in death within a year of metastasis for our patients," said John Kirkwood, MD, of the UPMC Hillman Cancer Center in Pittsburgh, in a . "The approval of Kimmtrak represents a major paradigm shift in the treatment of metastatic uveal melanoma and for the first time offers hope to those with this aggressive form of cancer."

Primary support for the approval came from the phase III randomized IMCgp100-202 trial involving 348 patients with untreated unresectable/metastatic uveal melanoma. Investigators randomized the patients 2:1 to tebentafusp or to a physician's choice of pembrolizumab (Keytruda), ipilimumab (Yervoy), or dacarbazine.

The primary endpoint was overall survival (OS), and the results showed that patients treated with tebentafusp had a median OS of 21.7 months versus 16.0 months for the control group, 82% of whom received the immune checkpoint inhibitor pembrolizumab. The difference represented a 49% reduction in the survival hazard (95% CI 0.37-0.71, P<0.0001).

Treatment-related adverse events with tebentafusp were manageable and consistent with the drug's proposed mechanism of action. The most common grade ≥3 adverse events in the tebentafusp arm were rash (18%), pruritus (5%), and pyrexia (4%). Grade 3 cytokine release syndrome (CRS) occurred in fewer than 1% of patients treated with tebentafusp. Labeling for the drug will include a boxed warning about the potential risks of CRS if not managed appropriately.

Tebentafusp is the first therapeutic agent targeting melanocytes to produce a survival benefit in a randomized trial, said Antoni Ribas, MD, of the University of California Los Angeles, following the initial report of the trial data during the American Association for Cancer Research meeting. "It's a practice-changing study, and we ought to be able to use this in practice."

According to the company's statement, tebentafusp should be available in the U.S. within weeks.

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