This protocol addresses first-line systemic treatment in patients with metastatic uveal melanoma who carry the HLA-A*02:01 allele, confirmed in peripheral blood — a genotypic characteristic that defines a distinct and actionable treatment population.
The patient presents with metastatic uveal melanoma and has confirmed HLA-A*02:01 allele positivity on peripheral blood testing. This HLA genotype is the central eligibility criterion that determines first-line systemic therapy selection in this setting.
A specific first-line systemic standard of care is established for HLA-A*02:01-positive patients with metastatic uveal melanoma. The protocol specifies how clinical factors — including the potential need for tumour debulking — may affect sequencing. The complete regimen, eligibility criteria, and decision algorithm are available in the full protocol.
The primary measurable objective is reduction of circulating tumour DNA (ctDNA) from baseline, including total clearance — a biomarker outcome associated with the overall survival benefit observed in long-term follow-up data.
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].
In a recent update with a minimum follow-up of 36 months, the OS benefit of tebentafusp was confirmed (27% versus 18% with investigator's choice) and was associated with the reduction of circulating tumour DNA (ctDNA) from baseline, including total clearance.
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