Multinational phase 3 trial of tebentafusp for metastatic uveal melanoma

Tebentafusp is a T-cell receptor-bispecific molecule that targets glycoprotein 100 and CD3. It is approved for adult patients who are positive fir HLA-A*02:01 and have unresectable or metastatic uveal melanoma. A multinational phase 3 trial randomized HLA-A*02:01-positive patients with previously untreated metastatic uveal melanoma to receive tebentafusp (tebentafusp group) or investigator’s choice of pembrolizumab, ipilimumab, or dacarbazine (control group). The primary end point was overall survival. At minimum follow-up of 36 months, median overall survival was 21.6 months in the tebentafusp group and 16.9 months in the control group (HR 0.68; 95% CI 0.54-0.87) with three-year OS rate 27% and 18%, respectively. The most common treatment-related adverse events of any grade in the tebentafusp group were rash, pyrexia, pruritus, and hypotension. Most tebentafusp-related adverse events occurred early during treatment, and no new events were observed with long-term administration. Discontinuation because of adverse events was low in the tebentafusp group (2% of patients) and in the control group (5%). No treatment-related deaths occurred. The auhors conclude that these results support the use of tebetafusp in this patient population.