Dr Sullivan on the Reduction of ctDNA With Tebentafusp in Metastatic Uveal Melanoma

Ryan J. Sullivan, MD, associate professor of medicine, Harvard Medical School, associate director. the Melanoma Program, Massachusetts General Cancer, discusses the early reduction of circulating tumor DNA (ctDNA) in patients with metastatic uveal melanoma treated with tebentafusp-tebn (Kimmtrak) and shares how these reductions could correlate with longer overall survival (OS) in patients with a best response of stable disease.

Tebentafusp displayed an OS benefit in patients with metastatic uveal melanoma, according to previous results from the phase 2 IMCgp100-102 trial (NCT02570308) and the phase 3 IMCgp100-202 trial (NCT03070392). In a study presented at the 2023 ASCO Annual Meeting, investigators evaluated patients treated with the bispecific T-cell engager in the phase 3 study to examine whether early on-treatment reduction in ctDNA may distinguish which patients with stable disease experienced long vs short OS.

In the tebentafusp arm, 202 patients had serum samples available from baseline and at 9 weeks from patients who were previously enrolled on the phase 3 trial, Sullivan begins. Notably, in the frontline setting, less patients with stable disease following frontline treatment had detectable ctDNA when compared with later-line settings, Sullivan explains, noting that this was not necessarily surprising, given that patients in later settings tend to have higher tumor burden.

Findings showed that 88% of all-comer patients treated with tebentafusp who had detectable ctDNA at baseline experienced a reduction in ctDNA at week 9. Additionally, 94% of patients with a best response of stable disease had a ctDNA reduction at week 9. Furthermore, 37% of all patients achieved a clearance of ctDNA. Notably, these patients responded more favorably than patients who did not achieve ctDNA clearance, Sullivan says. Moreover, 64% of responders cleared their ctDNA, Sullivan expands, adding 44% of the patients with stable disease cleared their ctDNA.