Real-world efficacy and toxicity of tebentafusp in metastatic uveal melanoma patients treated on the United Kingdom expanded access programme.

Metastatic uveal melanoma (mUM) carries a poor prognosis, with low response rates to checkpoint inhibitors. The phase III first-line IMCgp100-202 trial established tebentafusp, a bi-specific T cell engager, as the first treatment to demonstrate a survival benefit in mUM. Here, we report retrospective real-world efficacy and toxicity outcomes from the tebentafusp United Kingdom Expanded Access Programme (UK EAP). 115 HLA-A*02:01 positive patients with mUM were treated between July 2021 and June 2023. 10 of 18 UK EAP centres submitted data, and outcomes for 88 patients are reported here. Data was collected on demographics, disease characteristics, survival and treatment toxicities; and analysed to identify factors impacting on median overall survival (mOS), median progression-free survival (mPFS), occurrence of cytokine release syndrome (CRS) and grade 3/4 rash. 71% of patients were treated in the first-line setting with 94% having liver metastases. At a median follow-up of 12 months (range 0 to 34), mOS was 21 months (95% CI 17 to NR), and mPFS was 2.76 months (95% CI 2.53 to 3.22). The 12-month overall survival rate was 75% (95% CI 66.11-85.6%). Lower LDH and lower liver metastatic burden showed a trend towards improved overall survival, with baseline LDH ≥2x ULN conferring a very poor prognosis. Lower liver metastatic burden also associated with reduced frequency of CRS. No ≥ grade 3 toxicity was observed beyond dose 5. Tebentafusp on the UK EAP showed comparable real-world efficacy to the phase III first-line trial data, with manageable toxicities having implications for resource planning.