Document Type
Article
Presentation Date
12-1-2025
Abstract
PURPOSE: We conducted an integrated safety analysis from three clinical studies of tebentafusp, a first-in-class ImmTAC bispecific T-cell engager, which can redirect T cells to target glycoprotein 100-positive cells, in metastatic uveal melanoma.
EXPERIMENTAL DESIGN: HLA-A*02:01-positive patients with unresectable or metastatic uveal melanoma enrolled in three clinical trials (IMCgp100-01, IMCgp100-102, and IMCgp100-202) who received ≥1 dose of tebentafusp were included. Safety data were pooled to evaluate the profile, onset, and management of treatment-related adverse events (TRAE). Adverse events of special interest included cytokine release syndrome (CRS), acute skin reactions (ASR), and liver function test elevations. Primary prophylaxis with medications was not permitted.
RESULTS: Among 410 tebentafusp-treated patients, the most common TRAE were pyrexia (77%), pruritus (71%), and chills (53%). Most patients experienced CRS (88%), almost always mild (grade 1, 19%) to moderate (grade 2, 67%) in severity, with only 2% experiencing grade 3 (n = 6) or 4 (n = 1) CRS. Additionally, 92% had at least one ASR, primarily pruritus and rash, with 21% having a grade 3 event. Onset of CRS and ASR was within 1 to 2 days of infusion and generally reversible with standard interventions. Elevated liver function tests were generally mild and resolved without intervention. Most TRAE occurred following the first few infusions and diminished in frequency and severity with repeated dosing; no cumulative TRAE were detected. Discontinuations due to TRAE were rare (2%); there were no treatment-related deaths.
CONCLUSIONS: TRAE were consistent with tebentafusp's mechanism of action, mostly occurred during dose escalation, and were predictable, reversible, and manageable with appropriate surveillance and intervention.
Recommended Citation
Sato, Takami; Butler, Marcus O.; Piperno-Neumann, Sophie; Hassel, Jessica C.; Nathan, Paul; Shoushtari, Alexander N.; Rutkowski, Piotr; Carvajal, Richard D.; Baurain, Jean-Francois; Schlaak, Max; Piulats, Josep M.; Sullivan, Ryan J.; Ochsenreither, Sebastian; Dummer, Reinhard; Kirkwood, John M.; Ikeguchi, Alexandra; Joshua, Anthony M.; Middleton, Mark R.; Edukulla, Ramakrishna; Pfeiffer, Constance; and Sacco, Joseph J., "Incidence and Management of Adverse Events Associated With Tebentafusp Treatment in Metastatic Uveal Melanoma: Pooled Safety Analysis of 410 Patients" (2025). Kimmel Cancer Center Papers, Presentations, and Grand Rounds. Paper 85.
https://jdc.jefferson.edu/kimmelgrandrounds/85
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
Language
English
Comments
This article is the author's final published version in Clinical Cancer Research, Volume 31, Issue 23, 1 December 2025, Pages 5027–5036.
The published version is available at https://doi.org/10.1158/1078-0432.ccr-25-1513. Copyright © 2025 The Authors; Published by the American Association for Cancer Research.