FDA Approves Tebentafusp for Patients With Metastatic Uveal Melanoma and HLA-A*02:01


Tebentafusp has been approved by the FDA based on results of the phase 3 IMCgp100-202 trial for patients harboring HLA-A*02:01 with metastatic uveal melanoma.

The FDA has approved tebentafusp (Kimmtrak) for the treatment of adult patients with HLA-A*02:01–positive metastatic uveal melanoma, according to a press release from developer Immunocore Holdings Plc.1

Results of a pivotal trial indicated that the median overall survival (OS) in the tebentafusp group was statistically significantly higher than that of investigator choice therapy (HR, 0.51; 95% CI, 0.37-0.71; P <.0001). Tebentafusp is the first T-cell receptor bispecific antibody to receive approval from the FDA as treatment of a solid tumor as well as the first agent specifically approved for metastatic uveal melanoma.

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

The approval was supported by findings from the phase 3 IMCgp100-202 trial (NCT03070392), which were published in the New England Journal of Medicine in September 2021.2 The trial evaluated the efficacy of tebentafusp in patients who had untreated metastatic uveal melanoma.

In the trial, 378 patients were randomized 2:1 and received either tebentafusp (n = 252) or investigator choice of therapy (n = 125), which included single-agent pembrolizumab (Keytruda), ipilimumab (Yervoy), or dacarbazine. The study’s primary end point was OS in the intent-to-treat (ITT) population.

In the experimental arm, patients received 20 μg of tebentafusp on day 1, followed by 30 μg on day 8, and 68 μg on day 15 and weekly thereafter. In the investigator choice arm, patients received either pembrolizumab at 2 mg/kg every 3 weeks, ipilimumab at 3 mg/kg every 3 weeks, or dacarbazine at 1000 mg/m2 every 3 weeks.

The 1-year estimated OS rate in the ITT group was 73% for tebentafusp (95% CI, 66%-79%) compared with 59% (95% CI, 48%-67%) in the investigator choice group, with medians of 21.7 months and 16.0 months, respectively. Across pre-specified subgroups, an OS benefit was observed among those treated with tebentafusp.

Patients commonly experienced skin-related or cytokine-mediated treatment-related adverse effects (TRAEs) such as pyrexia, pruritus, and rash. However, after the first 3 to 4 doses, investigators noted a decrease in frequency of AEs. Typically, when using standard interventions, TRAEs were manageable. Discontinuation rates from TRAEs were less than 4% and there were no treatment-related deaths reported.

Immunocore has created an early access program for patients around the world to make treatment readily available. Currently, 200 patients in 13 countries are enrolled in the program.

“Until now, effective treatment options for metastatic uveal melanoma patients were virtually non-existent. The approval of [tebentafusp] 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,” Kyleigh LiPira, MBA, CEO of the Melanoma Research Foundation, concluded.


1. Immunocore announces FDA approval of Kimmtrak (tebentafusp-tebn) for the treatment of unresectable or metastatic uveal melanoma. News Releaase. Immunocore. January 26, 2022. Accessed January 26, 20221. https://yhoo.it/3KO59GU

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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