{"entity":{"id":"paper-imcgp100-202-n-engl-j-med-2021","kind":"paper","name":"Overall Survival Benefit with Tebentafusp in Metastatic Uveal Melanoma","aka":[],"tldr":"Published report from the IMCgp100-202 trial registered as NCT03070392, in New England Journal of Medicine (2021), chosen as the most cited paper whose own text cites the registry id.","summary":"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.\n\nMethods: 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.\n\nResults: 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.\n\nConclusions: 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.).\n\nIndexed on Europe PMC as PubMed record 34551229 (DOI 10.1056/nejmoa2103485). Its abstract cites the registry id NCT03070392, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"N Engl J Med 2021","url":"https://doi.org/10.1056/nejmoa2103485"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/34551229/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/34551229"},{"label":"ClinicalTrials.gov NCT03070392","url":"https://clinicaltrials.gov/study/NCT03070392"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["imcgp100-202"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2021,"doi":"10.1056/nejmoa2103485","pmid":"34551229","authors":"Nathan P, Hassel JC, Rutkowski P, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT03070392 with the most citations, so it is the natural first reading for anyone following the IMCgp100-202 trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},"route":"/key-papers/paper-imcgp100-202-n-engl-j-med-2021/","neighbours":{"trial":[{"id":"imcgp100-202","kind":"trial","name":"IMCgp100-202","route":"/trials/imcgp100-202/"}],"journal":[{"id":"nejm","kind":"journal","name":"New England Journal of Medicine","route":"/journals/nejm/"}],"idea":[{"id":"idea-prame-tcr-beyond-a02","kind":"idea","name":"TCR therapeutics for non-HLA-A*02 patients","route":"/ideas/idea-prame-tcr-beyond-a02/"}]}}