Overall Survival Benefit with Tebentafusp in Metastatic Uveal Melanoma
Paul Nathan, Jessica C Hassel, Piotr Rutkowski, Jean-Francois Baurain, Marcus O Butler, Max Schlaak, Ryan J Sullivan, Sebastian Ochsenreither, Reinhard Dummer, John M Kirkwood, Anthony M Joshua, Joseph J Sacco, Alexander N Shoushtari, Marlana Orloff, Josep M Piulats, Mohammed Milhem, April K S Salama, Brendan Curti, Lev Demidov, Lauris Gastaud, Cornelia Mauch, Melinda Yushak, Richard D Carvajal, Omid Hamid, Shaad E Abdullah, Chris Holland, Howard Goodall, Sophie Piperno-Neumann, IMCgp100-202 Investigators, Anthony Joshua, Michael Brown, Damien Kee, Jean-Francois Baurain, Marcus Butler, John Walker, Lauris Gastaud, Sophie Piperno-Neumann, Christoffer Gebhardt, Jessica Hassel, Cornelia Mauch, Friedegund Meier, Sebastian Ochsenreither, Max Schlaak, Jens Siveke, Jeffery Evans, Paul Nathan, Joseph Sacco, Paolo Antonio Ascierto, Michele Del Vecchio, Ellen Kapiteijn, Piotr Rutkowski, Lev Demidov, Svetlana Protsenko, Alfonso Berrocal, Luis De la Cruz Merino, Enrique Espinosa, Josep Maria Piulats, Carmela Rodriguez-Lopez, Reinhard Dummer, Igor Bondarenko, Valeriy Evgenovych Cheshuk, Yevhen Hotko, Eric Bernicker, Richard Carvajal, Sunandana Chandra, Bartosz Chmielowski, Brendan Curti, Jason Luke, Omid Hamid, Leonel Hernandez-Aya, Alexandra Ikeguchi, Kari Kendra, Kevin Kim, John Kirkwood, Jose Lutzky, Mohammed Milhem, Marlana Orloff, Igor Puzanov, Sunil Reddy, Matthew Rioth, April Salama, Alexander Shoushtari, Ryan Sullivan, Melinda Yushak, Paul Nathan, Jessica C Hassel, Piotr Rutkowski, Jean-Francois Baurain, Marcus O Butler, Max Schlaak, Ryan J Sullivan, Sebastian Ochsenreither, Reinhard Dummer, John M Kirkwood, Anthony M Joshua, Joseph J Sacco, Alexander N Shoushtari, Marlana Orloff, Josep M Piulats, Mohammed Milhem, April K S Salama, Brendan Curti, Lev Demidov, Lauris Gastaud, Cornelia Mauch, Melinda Yushak, Richard D Carvajal, Omid Hamid, Shaad E Abdullah, Chris Holland, Howard Goodall, Sophie Piperno-Neumann, IMCgp100-202 Investigators, Anthony Joshua, Michael Brown, Damien Kee, Jean-Francois Baurain, Marcus Butler, John Walker, Lauris Gastaud, Sophie Piperno-Neumann, Christoffer Gebhardt, Jessica Hassel, Cornelia Mauch, Friedegund Meier, Sebastian Ochsenreither, Max Schlaak, Jens Siveke, Jeffery Evans, Paul Nathan, Joseph Sacco, Paolo Antonio Ascierto, Michele Del Vecchio, Ellen Kapiteijn, Piotr Rutkowski, Lev Demidov, Svetlana Protsenko, Alfonso Berrocal, Luis De la Cruz Merino, Enrique Espinosa, Josep Maria Piulats, Carmela Rodriguez-Lopez, Reinhard Dummer, Igor Bondarenko, Valeriy Evgenovych Cheshuk, Yevhen Hotko, Eric Bernicker, Richard Carvajal, Sunandana Chandra, Bartosz Chmielowski, Brendan Curti, Jason Luke, Omid Hamid, Leonel Hernandez-Aya, Alexandra Ikeguchi, Kari Kendra, Kevin Kim, John Kirkwood, Jose Lutzky, Mohammed Milhem, Marlana Orloff, Igor Puzanov, Sunil Reddy, Matthew Rioth, April Salama, Alexander Shoushtari, Ryan Sullivan, Melinda Yushak
Abstract
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.).
Copyright © 2021 Massachusetts Medical Society.
Source: PubMed