This protocol addresses patients with metastatic uveal melanoma who carry the HLA-A*02:01 allele in peripheral blood and have progressed following first-line systemic treatment.
Tebentafusp is the established first-line systemic standard of care for HLA-A*02:01-positive patients with metastatic uveal melanoma (unless liver-directed treatment was required first for tumour debulking). This protocol is triggered when tebentafusp fails to achieve the intended reduction of circulating tumour DNA (ctDNA) from baseline, including total clearance.
Following tebentafusp progression, the preferred therapeutic options involve liver-directed modalities and systemic immunotherapy approaches, among other possibilities. The complete regimen, sequencing, and full evidence base are available via the link below.
DOI: 10.1016/j.esmoop.2026.106888
For HLA-A*02:01-positive patients, tebentafusp should be standard of care in the first-line metastatic setting unless liver-directed treatment modalities are required first for tumour debulking [I, A; ESMO-Magnitude of Clinical Benefit (ESMO-MCBS) v2.0 score: 3].
If these patients progress, liver-directed treatment modalities, anti-PD-1-based immunotherapies and clinical trial enrolment are the preferred therapeutic options [V, B].
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