Tebentafusp in advanced uveal melanoma: proof of principle for the efficacy of T-cell receptor therapeutics and bispecifics in solid tumors

Introduction Tebentafusp is a novel bispecific immune mobilizing T cell receptor (TCR)-based agent developed for the treatment of metastatic uveal melanoma, a highly fatal disease with no currently approved treatment options. Recent evidence suggests this drug may become the standard of care for first-line treatment of metastatic uveal melanoma. Areas Covered This review focuses on the development and investigation of tebentafusp for metastatic uveal melanoma. First, we discuss preclinical studies followed by clinical evaluation, culminating in a phase III trial showing improved overall survival with tebentafusp compared to standard of care. Finally, we expand upon key toxicities of tebentafusp and highlight biomarkers that may correlate with drug efficacy. Expert Opinion Tebentafusp provides a promising advancement to date for the management of metastatic uveal melanoma. Future studies should aim at identifying biomarkers that can predict treatment response or toxicity, combination therapy, application of tebentafusp in the adjuvant setting to reduce the risk of recurrence, and development of bispecifics with activity in other HLA subtypes. With its novel mechanism of action, degree of efficacy and safety profile, tebentafusp is expected to change the standard of care for treating metastatic and, potentially localized, uveal melanoma.