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Overall Survival Benefit with Tebentafusp in Metastatic Uveal Melanoma.

Publication ,  Journal Article
Nathan, P; Hassel, JC; Rutkowski, P; Baurain, J-F; Butler, MO; Schlaak, M; Sullivan, RJ; Ochsenreither, S; Dummer, R; Kirkwood, JM; Joshua, AM ...
Published in: N Engl J Med
September 23, 2021

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.).

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Published In

N Engl J Med

DOI

EISSN

1533-4406

Publication Date

September 23, 2021

Volume

385

Issue

13

Start / End Page

1196 / 1206

Location

United States

Related Subject Headings

  • Uveal Neoplasms
  • Survival Analysis
  • Recombinant Fusion Proteins
  • Middle Aged
  • Melanoma
  • Male
  • Ipilimumab
  • Humans
  • General & Internal Medicine
  • Female
 

Citation

APA
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Nathan, P., Hassel, J. C., Rutkowski, P., Baurain, J.-F., Butler, M. O., Schlaak, M., … IMCgp100-202 Investigators, . (2021). Overall Survival Benefit with Tebentafusp in Metastatic Uveal Melanoma. N Engl J Med, 385(13), 1196–1206. https://doi.org/10.1056/NEJMoa2103485
Nathan, Paul, Jessica C. Hassel, Piotr Rutkowski, Jean-Francois Baurain, Marcus O. Butler, Max Schlaak, Ryan J. Sullivan, et al. “Overall Survival Benefit with Tebentafusp in Metastatic Uveal Melanoma.N Engl J Med 385, no. 13 (September 23, 2021): 1196–1206. https://doi.org/10.1056/NEJMoa2103485.
Nathan P, Hassel JC, Rutkowski P, Baurain J-F, Butler MO, Schlaak M, et al. Overall Survival Benefit with Tebentafusp in Metastatic Uveal Melanoma. N Engl J Med. 2021 Sep 23;385(13):1196–206.
Nathan, Paul, et al. “Overall Survival Benefit with Tebentafusp in Metastatic Uveal Melanoma.N Engl J Med, vol. 385, no. 13, Sept. 2021, pp. 1196–206. Pubmed, doi:10.1056/NEJMoa2103485.
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. Overall Survival Benefit with Tebentafusp in Metastatic Uveal Melanoma. N Engl J Med. 2021 Sep 23;385(13):1196–1206.

Published In

N Engl J Med

DOI

EISSN

1533-4406

Publication Date

September 23, 2021

Volume

385

Issue

13

Start / End Page

1196 / 1206

Location

United States

Related Subject Headings

  • Uveal Neoplasms
  • Survival Analysis
  • Recombinant Fusion Proteins
  • Middle Aged
  • Melanoma
  • Male
  • Ipilimumab
  • Humans
  • General & Internal Medicine
  • Female