FDA Approves Tebentafusp-tebn in Adult HLA-A*02:01-Positive Unresectable/Metastatic Uveal Melanoma


Tebentafusp-tebn has been granted FDA approval to treat HLA-A*02:01-positive adult patients with unresectable or metastatic uveal melanoma based on positive results from a phase 3 study.

The FDA has granted approval to tebentafusp-tebn (Kimmtrak) for the treatment of patients with HLA-A*02:01-positive adult patients with unresectable or metastatic uveal melanoma, according to a press release issued by Immunocore Holdings plc.1

The approval is supported by data from the phase 3 IMCgp100-202 clinical trial, in which tebentafusp lead to prolonger overall survival (OS) in patients with previously untreated patients with metastatic uveal melanoma compared with the investigator’s choice of either Dacarbazine, ipilimumab (Yervoy), or pembrolizumab (Keytruda).

“Uveal melanoma is a devastating disease that has historically resulted in death within a year of metastasis for our patients,” said John Kirkwood, MD, director of the Melanoma Center at the UPMC Hillman Cancer Center, 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.”

In the phase 2 randomized, open-label, multi-center IMCgp100-202 study, 378 patients with metastatic uveal melanoma who were at least 18 years of age with histologically or cytologically confirmed disease, HLA A*0201 positive by central assay, had a life expectancy of at least 3 months, an ECOG performance status of 0 or 1, and measurable disease per RECIST v1.1 were included. The study population was evaluated for the primary end point of OS and multiple secondary end points including the number of patients with adverse events, progression-free survival (PFS), quality of life, pharmacokinetics, objective response rate, duration of response, and disease control rate.2

The hazard ratio for OS with tebentafusp compared with the investigator’s choice of therapy was in favor of tebentafusp (HR, 0.51; 95% CI, 0.37-0.71); P <.0001). At 1 year the OS rate with tebentafusp was 73% compared with 59% in the control group. The 6-month PFS was also longer inpatient treated with tebentafusp at 31% compared with 19% in the investigator’s choice arm (HR, 0.73; 95% CI, 0.58-0.94; P =.01).

In terms of safety, the most common treatment-related AEs observed with tebentafusp were cytokine-mediated events caused by T-cell activation and skin-related events caused by glycoprotein 100–positive melanocytes. The AEs specifically included rash (83%), pyrexia (76%), and pruritus (69%). Notably, the incidence of AEs decreased over time. Regarding grade 3 and 4 AEs, severity did lead to treatment discontinuation in2% of patients. There were no treatment-related deaths reported in the study.

The FDA approval for tebentafusp follows a breakthrough therapy designation unresectable or metastatic uveal melanoma and aligns with a Prescription User Fee Act target action date assigned to biologics license application which was granted priority review by the FDA in August 2021. Applications for the approval of tebentafusp as treatment of adult patients with HLA-A*02:01-positive metastatic uveal melanoma has also been submitted to the European Medicines Agency, the United Kingdom’s Medicines and Healthcare Regulatory Agency, Health Canada, and the Australian Government Department of Health Therapeutic Goods Administration

“Today’s approval of Kimmtrak is a historic milestone and the culmination of years of dedication by the Immunocore team, patients, and our healthcare partners. Every year in the United States, hundreds of people are diagnosed with metastatic uveal melanoma who, until now, had no approved treatment options. Kimmtrak is the first therapy to demonstrate a survival benefit to patients with this disease and we are focused on making KIMMTRAK available as quickly as possible, said Bahija Jallal, chief executive officer, Immunocore, in the press release. We’re also proud to have developed the world’s first approved TCR therapeutic, which we believe validates the strength of our platform and opens doors for us to explore further breakthrough discoveries in TCR therapeutics for the treatment of other cancers and diseases with high unmet need.”


1. Immunocore announces FDA approval of KIMMTRAK® (tebentafusp-tebn) for the treatment of unresectable or metastatic uveal melanoma. News release. January 26, 2022. Accessed January 26, 2022. https://bit.ly/33R85lC

2. Nathan P, Hassel JC, Rutkowski P, et al. Overall survival benefit with tebentafusp in metastatic uveal melanoma. N Engl J Med. 2021; 385:1196-1206. doi:10.1056/NEJMoa2103485

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