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The following is a summary of “Tebentafusp Induces a T-Cell–Driven Rash in Melanocyte-Bearing Skin as an Adverse Event Consistent with the Mechanism of Action,” published in the March 2025 issue of Journal of Investigative Dermatology by Hassel et al. 

Researchers conducted a retrospective study to investigate the mechanism of skin-related adverse events (SRAE), particularly rash, linked to tebentafusp, a gp100xCD3-bispecific ImmTAC.  

They examined clinical data from a randomized phase 3 trial (NCT03070392), comparing tebentafusp (252 individuals) with the investigator’s choice (126 individuals). Translational analyses were conducted using paired on-treatment skin samples from 19 individuals enrolled in the phase 1 trial (NCT01211262).  

The results showed that rash occurred as a clinical manifestation of tebentafusp-induced T cell recruitment to cutaneous melanocytes. Rash development was associated with baseline expression levels of gp100 and other melanin pathway genes in the skin. During treatment, melanocyte count declined, melanocytic gene expression decreased, and immune-related and cytokine signaling gene expression increased. After adjusting for baseline prognostic factors, individuals who developed a rash within the first week of tebentafusp treatment had comparable overall survival (OS) to those without a rash in the phase 3 randomized trial IMCgp100-202 (hazard ratio = 0.84, 95% CI = 0.53–1.32).  

Investigators concluded that skin rash resulting from tebentafusp treatment is an off-tumor, on-target effect related to its mechanism of action against gp100+ melanocytes. 

Source: jidonline.org/article/S0022-202X(24)01886-4/fulltext