Long-term Benefit of Tebentafusp in Untreated Uveal Melanoma

Tebentafusp, a T-cell receptor–bispecific molecule targeting glycoprotein 100 and CD3, has gained approval for adult patients (pts) positive for HLA-A*02:01 with unresectable or metastatic uveal melanoma. The primary analysis in the ongoing phase 3 trial established a significant long-term survival benefit associated with the use of tebentafusp.

Jessica C. Hassel and her team aimed to assess the therapeutic impact of tebentafusp in the context of unresectable or metastatic uveal melanoma.

Researchers performed an inclusive analysis of the 3-year efficacy and safety outcomes derived from an open-label, phase 3 trial. The study enrolled HLA-A*02:01–positive pts with previously untreated metastatic uveal melanoma, randomly assigning them in a 2:1 ratio to either the (tebentafusp group) or the (control group), wherein pts received the investigator’s choice of therapy involving pembrolizumab, ipilimumab, or dacarbazine. Randomization was stratified based on the lactate dehydrogenase level. The primary endpoint under scrutiny was overall survival (OS).

At a minimum follow-up of 36 months, the tebentafusp group exhibited a median OS of 21.6 months, surpassing the control group, which recorded 16.9 months (HR for death, 0.68; 95% confidence interval, 0.54 to 0.87). The estimated percentage of pts surviving at the 3-year mark was notably higher in the tebentafusp group at 27%, in contrast to the control group with 18%.

Within the tebentafusp group, common treatment-related adverse events (AEs) of any grade included rash (83%), pyrexia (76%), pruritus (70%), and hypotension (38%). Importantly, the majority of tebentafusp-related AEs occurred early during the treatment course, and no new adverse events emerged with long-term administration.

The percentage of pts who discontinued treatment due to AEs remained low in both groups, at 2% in the tebentafusp group and 5% in the control group). Additionally, it is noteworthy that no treatment-related deaths were reported, underscoring the overall safety profile of tebentafusp in this study.

The study concluded that the 3-year analysis substantiates a sustained, long-term benefit of tebentafusp for OS among adult HLA-A*02:01–positive pts diagnosed with previously untreated metastatic uveal melanoma.

The study is sponsored by Immunocore Ltd

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2304753

Clinical Trial: https://clinicaltrials.gov/study/NCT03070392

https://www.clinicaltrialsregister.eu/ctr-search/search?query=2015-003153-18

Hassel J C, Neumann S P, Rutkowski P, et al. (2023). “Three-Year Overall Survival with Tebentafusp in Metastatic Uveal Melanoma.”