Universität zu Köln

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 ORCID: 0000-0003-4663-6824, 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 and Piperno-Neumann, Sophie (2021). Overall Survival Benefit with Tebentafusp in Metastatic Uveal Melanoma. N. Engl. J. Med., 385 (13). S. 1196 - 1207. WALTHAM: MASSACHUSETTS MEDICAL SOC. ISSN 1533-4406

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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, ; EudraCT number, .) Tebentafusp for Uveal Melanoma Metastatic uveal melanoma is an aggressive disease without an established standard treatment. In a randomized trial that evaluated tebentafusp, a soluble T-cell receptor bispecific protein, overall survival at 1 year was 73% among patients who received tebentafusp, as compared with 59% among those who received the investigator's choice of therapy.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Nathan, Paul UNSPECIFIED UNSPECIFIED UNSPECIFIED Hassel, Jessica C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Rutkowski, Piotr UNSPECIFIED UNSPECIFIED UNSPECIFIED Baurain, Jean-Francois UNSPECIFIED UNSPECIFIED UNSPECIFIED Butler, Marcus O. UNSPECIFIED UNSPECIFIED UNSPECIFIED Schlaak, Max UNSPECIFIED UNSPECIFIED UNSPECIFIED Sullivan, Ryan J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Ochsenreither, Sebastian UNSPECIFIED UNSPECIFIED UNSPECIFIED Dummer, Reinhard UNSPECIFIED UNSPECIFIED UNSPECIFIED Kirkwood, John M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Joshua, Anthony M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Sacco, Joseph J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Shoushtari, Alexander N. UNSPECIFIED UNSPECIFIED UNSPECIFIED Orloff, Marlana UNSPECIFIED UNSPECIFIED UNSPECIFIED Piulats, Josep M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Milhem, Mohammed UNSPECIFIED orcid.org/0000-0003-4663-6824 UNSPECIFIED Salama, April K. S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Curti, Brendan UNSPECIFIED UNSPECIFIED UNSPECIFIED Demidov, Lev UNSPECIFIED UNSPECIFIED UNSPECIFIED Gastaud, Lauris UNSPECIFIED UNSPECIFIED UNSPECIFIED Mauch, Cornelia UNSPECIFIED UNSPECIFIED UNSPECIFIED Yushak, Melinda UNSPECIFIED UNSPECIFIED UNSPECIFIED Carvajal, Richard D. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hamid, Omid UNSPECIFIED UNSPECIFIED UNSPECIFIED Abdullah, Shaad E. UNSPECIFIED UNSPECIFIED UNSPECIFIED Holland, Chris UNSPECIFIED UNSPECIFIED UNSPECIFIED Goodall, Howard UNSPECIFIED UNSPECIFIED UNSPECIFIED Piperno-Neumann, Sophie UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-607296
DOI:	10.1056/NEJMoa2103485
Journal or Publication Title:	N. Engl. J. Med.
Volume:	385
Number:	13
Page Range:	S. 1196 - 1207
Date:	2021
Publisher:	MASSACHUSETTS MEDICAL SOC
Place of Publication:	WALTHAM
ISSN:	1533-4406
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language MULTICENTER; IMCGP100; CRITERIA Multiple languages Medicine, General & Internal Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/60729