Overall Survival Benefit with Tebentafusp in Metastatic Uveal Melanoma.
The New England journal of medicine
oregon; portland; providence cancer institute; chiles; eacri; Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Cytokine Release Syndrome; Dacarbazine; Exanthema; Female; Humans; Ipilimumab; Male; Melanoma; Middle Aged; Survival Analysis; Uveal Neoplasms
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
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.).
Nathan, Paul; Hassel, Jessica C; Rutkowski, Piotr; Baurain, Jean-Francois; Butler, Marcus O; Schlaak, Max; Sullivan, Ryan J; Ochsenreither, Sebastian; Dummer, Reinhard; Kirkwood, John M; Joshua, Anthony M; Sacco, Joseph J; Shoushtari, Alexander N; Orloff, Marlana; Piulats, Josep M; Milhem, Mohammed; Salama, April K S; Curti, Brendan; Demidov, Lev; Gastaud, Lauris; Mauch, Cornelia; Yushak, Melinda; Carvajal, Richard D; Hamid, Omid; Abdullah, Shaad E; Holland, Chris; Goodall, Howard; Piperno-Neumann, Sophie; and IMCgp100-202 Investigators, "Overall Survival Benefit with Tebentafusp in Metastatic Uveal Melanoma." (2021). Articles, Abstracts, and Reports. 5290.