Originally published by 2 Minute Medicine^® (view original article). Reused on AccessMedicine with permission.

1. Across a median follow-up of 48.5 months, usage of tebentafusp for patients with metastatic uveal melanoma was associated with a median OS that was double those observed historically in similar patient populations.

2. Low circulating-tumour DNA (ctDNA) levels at baseline and greater reductions in ctDNA levels at week 9 of treatment were associated with improved OS.

Evidence Rating Level: 1 (Excellent)

Metastatic uveal melanoma (mUM) has historically been associated with a poor prognosis owing to a lack of treatment options and an agreed-upon standard of care. Tebentafusp, a novel ImmTAC (Immune mobilizing monoclonal T-cell receptor Against Cancer) drug, has shown favourable survival outcomes in previously untreated mUM and treatment-refractory mUM. This single-arm, international, phase 1/2 study therefore sought to investigate the efficacy and safety of tebentafusp at 4 years of follow-up which represents the longest follow-up data to date. Patients over 18 years of age with a confirmed diagnosis of mUM and a life expectancy greater than 3 months were placed into either dose escalation (n = 19) or expansion cohorts (n = 127). The main efficacy outcome of interest was overall survival (OS). Baseline, 5-week and 9-week serum circulating-tumour DNA (ctDNA) levels were assessed to examine potential predictors of tebentafusp efficacy. The median OS was 17.4 months (95% CI = 13.1 to 22.8 months). Median OS rates in the expansion phase cohort at 1, 2, 3 and 4 years were nearly double those reported in a recent meta-analysis of other treatment modalities in mUM, with a hazard ratio of 0.54 (95% CI = 0.42 to 0.69) favouring tebentafusp. Further, low or undetectable levels of ctDNA at baseline, as well as greater reductions in ctDNA levels by week 9 were associated with improved OS. Overall, this study found that patients with mUM treated with tebentafusp showed median OS rates that were approximately double those observed historically in similar patient populations, and that ctDNA levels may be a reliable biomarker of response for tebentafusp.

Click to read the study in BMJ

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