FDA Approves Tebentafusp to Treat HLA-A*02:01 Positive Uveal Melanoma


Tebentafusp is now the first FDA-approved therapy to treat unresectable or metastatic uveal melanoma.

The FDA has approved tebentafusp-tebn (Kimmtrak) for the indication of unresectable or metastatic uveal melanoma in adult patients whose disease harbors HLA-A*02:01.1 The regulatory decision represents both the first FDA-approved therapy to treat unresectable or metastatic uveal melanoma, as well as the first FDA-approved T-cell receptor therapeutic.

The approval is supported by findings from the phase 3 IMCgp100-202 trial (NCT03070392) which demonstrated that patients who received this drug achieved significantly improved overall survival at 1 year of follow-up compared with investigators choice of therapy (HR, 0.51; 95% CI, 0.37-0.71; P <.0001).

Overall, 378 patients with previously untreated metastatic uveal melanoma were randomized 2:1 to receive either tebentafusp or investigators choice of pembrolizumab (Keytruda), ipilimumab (Yervoy), or dacarbazine. At a 6-month follow-up, progression free survival (PFS) was also significantly higher among patients in the tebentafusp group than in the control group (31% vs 19%; HR, 0.73; 95% CI, 0.58-0.94; P = .01).2

“Uveal melanoma is a devastating disease that has historically resulted in death within a year of metastasis for our patients,” John Kirkwood, MD, director of the Melanoma Center at the UPMC Hillman Cancer Center, said in a press release. “The approval of Kimmtrak [tebentafusp-tebn] 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.”

The most common grade 3 or worse adverse events (AEs) included rash (18%), pyrexia (4%), and pruritus (5%). Approximately less than 1% of patients experienced grade 3 cytokine release syndrome (CRS); however, this was reported to be well managed. A consequent warning for CRS will be included in the label due to its ability to become serious or life-threatening.

Manifestations for CRS may include fever, hypotension, hypoxia, chills, nausea, vomiting, rash, elevated transaminases, fatigue, and headache. Immediate access to mediations and resuscitative equipment is crucial for managing CRS. Patients should be euvolemic prior to beginning any infusions. Furthermore, patients should be monitored for fluid status, vital signs, and oxygen levels. In the event of persistent and severe CRS, tebentafusp should be withheld or discontinued.

Skin reactions and elevated liver enzymes were also frequently observed. If skin reactions occur, patients should be administered antihistamine and topical or systemic steroids based on persistence and severity of symptoms. Providers should also monitor alanine aminotransferase (ALT), aminotransferase (AST), and total blood bilirubin prior to the start of and throughout treatment to watch for elevated liver enzymes.

No grade 4 or fatal events were observed throughout the phase 3 trial.

“Until now, effective treatment options for metastatic uveal melanoma patients were virtually non-existent,” concluded Kyleigh LiPira, MBA, CEO of the Melanoma Research Foundation. “The approval of Kimmtrak represents not only a new therapy but a new hope for the individuals and the families of those diagnosed with the deadliest form of eye cancer.”


  1. Immunocore announces FDA approval of Kimmtrak (tebentafusp-tebn) for the treatment of unresectable or metastatic uveal melanoma. News release. Immunocore Holdings Limited; January 26, 2022. Accessed January 26, 2022. https://yhoo.it/3r1C3fk
  2. Nathan P, Hassel JC, Rutkowski P, et al. Overall survival benefit with tebentafusp in metastatic uveal melanoma. N Engl J Med. 2021;385(13):1196-1206. doi:10.1056/NEJMoa2103485

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