Second-Line Treatment of Amelanocytic Melanoma in Unresectable Stage III or Stage IV Disease with Absent BRAF V600 Mutation

This protocol applies to patients with unresectable stage III or stage IV (metastatic) cutaneous melanoma whose tumour does not carry a BRAF V600 mutation — classified as BRAF wild-type disease.

The absence of a BRAF V600 mutation directly shapes the available treatment landscape, as BRAF-targeted therapy is not an applicable option for this population.

PD-1 blockade is a standard-of-care option for all patients with advanced melanoma in the first-line setting, regardless of BRAF status. However, for patients with BRAF wild-type tumours specifically, the range of approved options in the second-line setting is considerably more limited — making careful protocol selection especially important.

Management in the second-line setting centres on immunotherapy, with multiple regimen options — including combination and monotherapy approaches — considered based on what was used in the first line. In a carefully defined subset of patients, a specialised cell-based therapy may also be an option.