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Review
. 2023 Mar 21:15:17588359231160140.
doi: 10.1177/17588359231160140. eCollection 2023.

Tebentafusp: a first-in-class treatment for metastatic uveal melanoma

Sarah Howlett  1 , Thomas J Carter  1 , Heather M Shaw  1   2 , Paul D Nathan  3
Affiliations
Review

Tebentafusp: a first-in-class treatment for metastatic uveal melanoma

Sarah Howlett et al. Ther Adv Med Oncol. .

Abstract

Tebentafusp is a first-in-class immunotherapy agent that comprises an engineered T-cell receptor targeting a gp100 epitope presented by human leukocyte antigen-A*02:01 cells, fused to an anti-CD3 single-chain variable fragment. Tebentafusp is both the first bispecific T-cell engager to show efficacy in the treatment of advanced solid cancer and the first anti-cancer treatment to demonstrate an overall survival benefit in patients with uveal melanoma (UM). This review article will focus on the clinical development of tebentafusp, the mechanism of action and resultant evolution of the management of advanced UM.

Keywords: ImmTAC; gp100; metastatic; tebentafusp; uveal melanoma.

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Conflict of interest statement

The authors declare that there is no conflict of interest.

Figures

Figure 1.
Figure 1.
Theories behind poor ICPI response in UM.–, ICPI, immune checkpoint inhibitor; UM, uveal melanoma.
Figure 2.
Figure 2.
(a) Structure of ImmTAC – a soluble TCR domain and an anti-CD3 scFv domain joined by a disulphide linker. (b) Schematic demonstrating the mechanism of action of tebentafusp: The TCR domain binds HLA-A*02:01-positive melanoma cells presenting a melanoma-associated antigen gp100-derived peptide, and the anti-CD3 scFv recruits T cells. HLA, human leukocyte antigen; ImmTAC, immune mobilising monoclonal T-cell receptors against cancer; scFv, single-chain variable fragment; TCR, T-cell receptor.
Figure 3.
Figure 3.
(a) Management algorithm for cytokine-mediated hypotension following tebentafusp administration. Patients on antihypertensives should omit these for 48 h before, and 24 h after treatment with tebentafusp for the first few doses. (b) Stepwise management of pyrexia. SBP = systolic blood pressure, IV = intravenous, PO = oral, TDS = three times daily, QDS = four times daily, CI = contraindication.
Figure 4.
Figure 4.
Management of skin toxicity (pruritus). IV = intravenous, PO = oral, QDS = four times daily, PRN = as needed.
See this image and copyright information in PMC

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