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Abstract CT029: Five-year survival with tebentafusp in previously untreated metastatic uveal melanoma in a phase 3 trial
Abstract   Peer reviewed

Abstract CT029: Five-year survival with tebentafusp in previously untreated metastatic uveal melanoma in a phase 3 trial

Paul Nathan, Sophie Piperno-Neumann, Jessica C. Hassel, Marcus O. Butler, Max Schlaak, Ryan J. Sullivan, Reinhard Dummer, John M. Kirkwood, Joseph J. Sacco, Alexander N. Shoushtari, …
Cancer research (Chicago, Ill.), Vol.86(8_Supplement), pp.CT029-CT029
04/17/2026
DOI: 10.1158/1538-7445.AM2026-CT029

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Abstract

Background: Metastatic uveal melanoma (mUM) has a very poor prognosis with a historical survival rate of <10% at 5 yrs. Tebentafusp, a first in class ImmTAC bispecific (gp100 x CD3), is approved for adult HLA-A*02:01+ patients with unresectable or mUM based on a phase 3 study demonstrating improved overall survival (OS) compared to investigator’s choice (IC) (HR 0.51; IMCgp100-202; NCT03070392). This benefit was maintained at the 3-yr follow-up (HR 0.68), with a 3-yr OS rate of 27% for tebentafusp and 18% for IC. Molecular response assessed by ctDNA reduction was a better indicator of OS benefit than traditional RECISTv1.1 measurements. Here we report updated analyses of OS after a minimum follow-up of 5 yrs. Methods: In this randomized, open-label, Phase 3 trial, first line HLA-A*02:01+ mUM patients were randomized 2:1 to receive tebentafusp or IC of single-agent pembrolizumab, ipilimumab or dacarbazine, stratified by lactate dehydrogenase. Primary endpoint was OS. ctDNA reduction was an exploratory endpoint. OS was estimated using Kaplan-Meier methods and treatment effects compared using Cox proportional hazards model. A Cox model, adjusted for baseline and time-varying covariates at progression, compared post-progression survival in tebentafusp patients with versus without treatment beyond radiographic progression (TBP). Results: 378 patients were randomized to tebentafusp (252) or IC (126; 82% pembrolizumab). With extended follow-up, the OS continued to favor tebentafusp, with a stratified hazard ratio of 0.67 (95% CI, 0.54-0.85). The 5-year OS rate for tebentafusp was 16% (95% CI, 11-21) vs 8% (95% CI, 4-14) for IC. The OS benefit was evident even in patients with known poor prognostic factors, including those with large tumors ≥ 10 cm. OS benefit was also seen in patients who did not have radiographic response including those with best response of progressive disease (PD) or those with a best change of tumor growth (>20%). Notably, in the tebentafusp arm, TBP was associated with better OS compared to no TBP, even after adjusting for covariates (HR 0.61; 95% CI, 0.44-0.83). In tebentafusp-treated patients, longer OS was associated with undetectable ctDNA at baseline or ctDNA reductions ≥50% by week 9. Among 21 ctDNA-evaluable patients who survived ≥ 5 years, 15 had undetectable baseline ctDNA and the remaining 6 had ctDNA clearance. Deep reductions in ctDNA were seen in patients regardless of baseline tumor burden and across all RECIST categories. Conclusions: Tebentafusp demonstrates durable, long-term OS benefit in first line HLA-A*02:01+ patients, which at 5 years is the longest OS follow-up in a randomized trial in mUM. OS benefit is evident in those with poor prognostic factors and remains independent of radiographic response, with ctDNA levels proving to be a better indicator of activity. This is the first report of long-term OS benefit in a solid tumor treated with an ImmTAC therapy.

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