Tebentafusp (gp100×CD3 ImmTAC) Doubles 5-Year OS to 16% in HLA-A*02:01+ Metastatic Uveal Melanoma

Tebentafusp is a first-in-class TCR–anti-CD3 bispecific fusion protein (ImmTAC) that redirects T cells to gp100 peptide presented by HLA-A02:01 on uveal melanoma cells. In the international, open-label Phase 3 IMCgp100-202 trial (NCT03070392), previously untreated HLA-A02:01+ metastatic/unresectable uveal melanoma patients were randomized 2:1 to tebentafusp vs investigator’s choice pembrolizumab, ipilimumab, or dacarbazine (n=378 total; tebentafusp n=252, control n=126); at ≥5 years’ follow-up, median OS was 21.6 vs 16.9 months (HR 0.67; 95% CI 0.54–0.85) and 5-year OS was 16% vs 8%—notably outperforming historical outcomes with single-agent PD-1/CTLA-4 or dacarbazine in this disease (generally low response rates and median OS often in the ~10–16 month range, depending on regimen and selection). Post hoc analyses linked longer OS with on-treatment ctDNA reductions (≥50% by week 9) and suggested a potential OS advantage for treatment beyond RECIST progression, underscoring that radiographic response may under-call benefit in this modality.