Overall Survival Benefit with Tebentafusp in Metastatic Uveal Melanoma.

Journal Article (Clinical Trial, Phase III;Journal Article;Multicenter Study)

BACKGROUND: Uveal melanoma is a disease that is distinct from cutaneous melanoma, with a low tumor mutational burden and a 1-year overall survival of approximately 50% in patients with metastatic uveal melanoma. Data showing a proven overall survival benefit with a systemic treatment are lacking. Tebentafusp is a bispecific protein consisting of an affinity-enhanced T-cell receptor fused to an anti-CD3 effector that can redirect T cells to target glycoprotein 100-positive cells. METHODS: In this open-label, phase 3 trial, we randomly assigned previously untreated HLA-A*02:01-positive patients with metastatic uveal melanoma in a 2:1 ratio to receive tebentafusp (tebentafusp group) or the investigator's choice of therapy with single-agent pembrolizumab, ipilimumab, or dacarbazine (control group), stratified according to the lactate dehydrogenase level. The primary end point was overall survival. RESULTS: A total of 378 patients were randomly assigned to either the tebentafusp group (252 patients) or the control group (126 patients). Overall survival at 1 year was 73% in the tebentafusp group and 59% in the control group (hazard ratio for death, 0.51; 95% confidence interval [CI], 0.37 to 0.71; P<0.001) in the intention-to-treat population. Progression-free survival was also significantly higher in the tebentafusp group than in the control group (31% vs. 19% at 6 months; hazard ratio for disease progression or death, 0.73; 95% CI, 0.58 to 0.94; P = 0.01). The most common treatment-related adverse events in the tebentafusp group were cytokine-mediated events (due to T-cell activation) and skin-related events (due to glycoprotein 100-positive melanocytes), including rash (83%), pyrexia (76%), and pruritus (69%). These adverse events decreased in incidence and severity after the first three or four doses and infrequently led to discontinuation of the trial treatment (2%). No treatment-related deaths were reported. CONCLUSIONS: Treatment with tebentafusp resulted in longer overall survival than the control therapy among previously untreated patients with metastatic uveal melanoma. (Funded by Immunocore; ClinicalTrials.gov number, NCT03070392; EudraCT number, 2015-003153-18.).

Full Text

Duke Authors

Cited Authors

  • Nathan, P; Hassel, JC; Rutkowski, P; Baurain, J-F; Butler, MO; Schlaak, M; Sullivan, RJ; Ochsenreither, S; Dummer, R; Kirkwood, JM; Joshua, AM; Sacco, JJ; Shoushtari, AN; Orloff, M; Piulats, JM; Milhem, M; Salama, AKS; Curti, B; Demidov, L; Gastaud, L; Mauch, C; Yushak, M; Carvajal, RD; Hamid, O; Abdullah, SE; Holland, C; Goodall, H; Piperno-Neumann, S; IMCgp100-202 Investigators,

Published Date

  • September 23, 2021

Published In

Volume / Issue

  • 385 / 13

Start / End Page

  • 1196 - 1206

PubMed ID

  • 34551229

Electronic International Standard Serial Number (EISSN)

  • 1533-4406

Digital Object Identifier (DOI)

  • 10.1056/NEJMoa2103485


  • eng

Conference Location

  • United States