In an analysis presented at the European Society for Medical Oncology (ESMO) Congress 2023 (Abstract LBA50) and reported in The New England Journal of Medicine by Jessica C. Hassel, MD, and colleagues, overall survival at 3 years in the phase III IMCgp100-202 trial continued to favor tebentafusp-tebn over investigator’s choice of treatment in previously untreated patients with HLA-A*02:01–positive unresectable or metastatic uveal melanoma.
The primary analysis of overall survival supported the January 2022 approval of tebentafusp in this setting (hazard ratio [HR] vs investigator choice of treatment = 0.51, 95% confidence interval [CI] = 0.37–0.71, P < .0001).
Jessica C. Hassel, MD
Study Details
In the open-label international trial, 378 patients enrolled between March 2017 and June 2020 were randomly assigned 2:1 to receive tebentafusp at 68 μg weekly after step-up doses of 20 μg on day 1 and 30 μg on day 8 (n = 252) or investigator’s choice (n = 126) of 21-day cycles of pembrolizumab (2 mg/kg on day 1; n = 103), ipilimumab (3 mg/kg on day 1 for a maximum of four doses; n = 16), or dacarbazine (1,000 mg/m2 on day 1; n = 7). Except for ipilimumab, treatment was continued until disease progression or unacceptable toxicity.
Key Findings
At a minimum follow-up of 36 months, median overall survival was 21.6 months (95% CI = 19.0–24.3 months) in the tebentafusp group vs 16.9 months (95% CI = 12.9–19.5 months) in the control group (HR = 0.68, 95% CI = 0.54–0.87). Rates at 1, 2, and 3 years were 72% vs 60%, 45% vs 30%, and 27% vs 18%, respectively.
Objective response rates were 11% in the tebentafusp group vs 5% in the control group (odds ratio = 2.46, 95% CI = 1.00-6.06). Median progression-free survival was 3.4 months (95% CI = 3.0-5.4 months) in the tebentafusp group vs 2.9 months (95% CI = 2.8- 3.0 months) in the control group (HR = 0.76, 95% CI = 0.60–0.97).
The safety profile of tebentafusp remained consistent with that seen in the primary analysis, with no new types of adverse events being observed with longer-term treatment. No treatment-related deaths were reported in the trial.
The investigators concluded: “This 3-year analysis supported a continued long-term benefit of tebentafusp for overall survival among adult HLA-A*02:01–positive patients with previously untreated metastatic uveal melanoma.”
Paul Nathan, MD, PhD, of Mount Vernon Cancer Centre, Northwood, UK, is the corresponding author for The New England Journal of Medicine article.
Disclosure: The study was funded by Immunocore. For full disclosures of the study authors, visit nejm.org.
