Incidence and Management of Adverse Events Associated with Tebentafusp Treatment in Metastatic Uveal Melanoma: Pooled Safety Analysis of 410 patients.

PURPOSE: We conducted an integrated safety analysis from three clinical studies of tebentafusp, a first-in-class ImmTAC bispecific T cell engager, that can redirect T cells to target glycoprotein 100-positive cells, in metastatic uveal melanoma (mUM). EXPERIMENTAL DESIGN: HLA-A*02:01-positive patients with unresectable or mUM enrolled in three clinical trials (IMCgp100-01; IMCgp100-102; 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 (TRAEs). AEs of special interest (AESIs) included cytokine release syndrome (CRS), acute skin reactions (ASR), and liver function test (LFT) elevations. Primary prophylaxis with medications was not permitted. RESULTS: Among 410 tebentafusp-treated patients, the most common TRAEs 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 were within 1-2 days of infusion and generally reversible with standard interventions. Elevated LFTs were generally mild and resolved without intervention. Most TRAEs occurred following the first few infusions and diminished in frequency and severity with repeated dosing; no cumulative TRAEs were detected. Discontinuations due to TRAEs were rare (2%); there were no treatment-related deaths. CONCLUSIONS: TRAEs were consistent with tebentafusp's mechanism of action, mostly occurred during dose escalation, and were predictable, reversible, and manageable with appropriate surveillance and intervention.