Multinational phase 3 study of tebentafusp for metastatic uveal melanoma: five-year overall survival results

Tebentafusp is a bispecific gp100 peptide HLA-directed CD3 T cell engager that demonstrated an overall survival benefit compared to investigator’s choice in a phase 3 trial in previously untreated HLA-A*02:01-positive adult patients with unresectable or metastatic uveal melanoma (mUM). Final 5-year analysis of overall survival has now been published. Patients were randomized to receive tebentafusp or investigator’s choice of pembrolizumab, ipilimumab, or dacarbazine (control group). At a minimum of 5 years follow-up, median overall survival was 21.6 months in the tebentafusp group and 16.9 month in the control group (sHR 0.67; 95% CI 0.54-0.85) with OS at 5 years 16% versus 8%, respectively. Tebentafusp improved survival even in poor-prognosis groups, such as patients with baseline tumors ≥ 10 cm or those whose best response was progressive disease. In the tebentafusp group, longer overall survival was associated with undectable ctDNA at baseline or ctDNA reductions ≥ 50% by week 9. The authors conclude that tebentafusp continues to provide long-term survival benefit in previously untreated HLA-A*02:01-positive mUM patients.