Online first
Review paper
Published online: 2025-03-12
Tebentafusp (IMCgp100) in the treatment of uveal melanoma — from preclinical evidence to clinical practice
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Abstract
Tebentafusp (IMCgp100) is a novel bispecific immunotherapy that contains a specifically engineered soluble T-cell receptor (TCR) capable of recognising the gp100 epitope on the surface of tumour cells presented by human leukocyte antigen-A*02:01 (HLA- A*02:01 (HLA-A2) is a specific allele within the HLA-A2 group). The HLA-A2 is then fused to the single-chain variable fragment of anti-CD3, which binds to T-cells and destroys them. Tebentafusp has been shown to cause a significant increase in pro-inflammatory cytokine levels that are detrimental to the tumour. The preliminary results of tebentafusp in solid tumours are encouraging, particularly in advanced/metastatic uveal melanoma (UM). In a randomised phase III study (IMCgp100-202; N = 378), patients with untreated HLA*02:01 positive metastatic UM (mUM), tebentafusp significantly improved overall survival (OS) with a hazard ratio (HR) of 0.51 compared to the investigator's choice, mainly pembrolizumab (82%). The one-year OS rate for tebentafusp was 73% compared to 59% for pembrolizumab. For comparison, the single-arm GEM1402 study (N = 52) reported a one-year OS rate of 52% for the combination of nivolumab and Ipilimumab in metastatic UM. The most common adverse reactions related to tebentafusp include cytokine release syndrome (CRS) and dermatological reactions such as rash. It is the first drug with OS benefit in advanced/metastatic UM patients. However, further research is needed to optimise its use, improve patient selection, develop combination therapies and identify predictive and prognostic biomarkers.
Keywords: tebentafuspmetastatic uveal melanomaIMCgp100immunotherapygp100bispecific T-cell receptor therapy
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