Dr Sullivan on ctDNA Reduction After Tebentafusp Treatment in Uveal Melanoma

Ryan J. Sullivan, MD, associate professor, medicine, Harvard Medical School; associate professor, hematology/oncology, Massachusetts General Hospital, discusses findings from a study investigating the effects of early circulating tumor DNA (ctDNA) reduction on overall survival (OS) in patients with uveal melanoma treated with tebentafusp-tebn (Kimmtrak).

In this trial, patients with metastatic uveal melanoma received 68 mcg of intravenous tebentafusp weekly after dose escalation. The investigators collected sera from 202 patients at baseline and week 9 and analyzed the sera for ctDNA mutations using a 15-gene targeted assay. Of these patients, 61% had detectable ctDNA mutations at baseline.

By week 9 of tebentafusp treatment, 88% of patients with previously untreated disease had reduced ctDNA levels, 44% had at least a 50% reduction in ctDNA levels, and 37% had total ctDNA clearance. The patients with detectable ctDNA at baseline who achieved total ctDNA clearance with tebentafusp treatment were more likely to survive longer than those without total clearance, Sullivan says.

Additionally, the 16 previously treated patients with progressive disease who achieved at least a 50% reduction in their ctDNA levels with tebentafusp had an OS benefit vs those with less than a 50% reduction, with a hazard ratio of 0.48. This finding indicates that if a patient receiving tebentafusp has significantly lower ctDNA levels despite new or growing disease, they may benefit from continuing tebentafusp therapy, Sullivan explains. Although there are currently no data to directly support continued ctDNA monitoring in these patients, the findings from this study show the potential benefits of following patient ctDNA levels using commercial assays to derive additional information regarding tebentafusp efficacy, which can inform whether a patient should continue to receive tebentafusp or switch to a different approach, Sullivan emphasizes. ctDNA assays may reveal continued benefits from tebentafusp that traditional imaging does not detect, Sullivan concludes.