Early ctDNA Testing Provides Another Tool for Predicting Survival Outcomes With Tebentafusp in Metastatic Uveal Melanoma

Source: OncLive, May 2023

The incorporation of circulating tumor DNA (ctDNA) testing into standard practice for patients with metastatic uveal melanoma receiving tebentafusp-tebn (Kimmtrak) may provide a more accurate assessment of the agent’s efficacy compared with radiographic response, and better inform the decision to continue or discontinue treatment, according to Ryan J. Sullivan, MD.

According to prior results from the phase 2 trial IMCgp100-102 trial (NCT02570308), the bispecific T-cell engager tebentafusp improved overall survival (OS) in patients with previously treated metastatic uveal melanoma regardless of their RECIST v1.1 best response. Subsequent exploratory analysis suggested that early reduction in ctDNA levels was a better indicator of patients’ long-term OS benefit than radiographic-based response criteria.

Analysis of ctDNA in the phase 3 IMCgp100-202 trial (NCT03070392) of patients with previously untreated metastatic uveal melanoma receiving first-line tebentafusp confirmed that a deeper reduction in ctDNA levels was associated with longer OS.Of the 123 evaluable patients with detectable ctDNA (n = 123/202) at baseline, 88% experienced ctDNA reduction by week 9 of treatment. Notably, these patients achieved an overall response rate equating to only 10%. One-year OS rates for patients with undetectable and detectable ctDNA were 90% and 62%, respectively (HR, 0.43; 95% CI, 0.28-0.67). These findings were presented at the 2023 AACR Annual Meeting.1