Low Dose Dexamethasone for the Prevention of Cytokine Release Syndrome Associated With Tebentafusp

This is a single-arm multi-site phase II study of prophylactic low-dose dexamethasone premedication in patients receiving tebentafusp per standard of care for HLA-A\*02:01-positive advanced uveal melanoma. Dexamethasone doses (2 and 4 mg) will be tested sequentially per a Simon's optimal two-stage design. Tebentafusp is a first-in-class, bispecific gp100 peptide and CD3 T-cell engager shown to improve overall survival of HLA-A\*02:01-positive patients with untreated, advanced uveal melanoma. The most common treatment-related adverse event associated with tebentafusp is cytokine release syndrome. Given the significant patient and health system burden of cytokine release syndrome in tebentafusp-treated patients, the investigators plan to use prophylactic low-dose dexamethasone premedication. The investigators hypothesize that this strategy will decrease the incidence and severity of cytokine release syndrome. Improvements in the safety and tolerability of tebentafusp could enable broader use of tebentafusp in outpatient and community settings and reduce hospitalization-related costs and barriers to care.