Real world experience of bispecific fusion protein in patients with metastatic uveal melanoma: Can we deliver?

Abstract

e21504 Background: Effective treatments for patients with metastatic uveal melanoma has remained a longstanding unmet need. Poor response rates to checkpoint inhibitors has increased the need for patients to access new ways of targeting this disease. Tebentafusp is a first in class T Cell receptor bispecific fusion protein that has demonstrated an overall survival benefit. However although licensed it has yet to be approved in the UK for wider use. Methods: Prospective data collection on five patients receiving tebentafusp through the Managed Access Programme at a cancer centre that had not taken part in any trials of this therapy before. Patients were permitted with metastatic uveal melanoma; ECOG performance status 0-1 and were HLA-A*02:01 positive. Protocols were disseminated across the wider cancer teams for the management of side effects including cytokine release syndrome. Patients received extended monitoring for at least 16 hours, and vital signs (blood pressure, heart rate, temperature and pulse oximetry) taken every 2-4 hours. Drop in systolic BP < 20mmHg treated with IV fluids. Results: Five patients with advanced uveal melanoma participated in the Access Programme at one cancer site to assess efficacy, tolerability and workforce upskilling and capability with a first in class bispecific fusion protein therapy. All patients were HLA-A*02:01 positive. The patients commenced therapy between November 2021 and July 2023. All were male; median age 66. Four patients developed cytokine release syndrome commencing at cycle one. These patients required intravenous fluids for CRS grade 2, no patients required vasopressors. One patient required IV hydrocortisone. Four patients developed skin toxicity. These were managed with antihistamines and steroids. Three patients stopped due to confirmed disease progression, receiving 2-7 cycles; one made an informed decision to stop due to grade 3 skin toxicity. One patient continues on tebentafusp and has received 32 cycles to date. They recently had treatment paused for ablation and resection of oligometastatic disease that found residual uveal melanoma and have restarted. Conclusions: Real-world data suggests that using a gp100-targeting TCR/anti-CD3 bispecific fusion protein is tolerated and deliverable in new settings. Tebentafusp was delivered without any medical emergencies and CRS was successfully managed with proactive fluid management and steroids. The rate and grading of side effects reflects that described in the large randomised controlled trial. Patients with uveal melanoma can derive ongoing clinical benefit - including one patient who has received 32 cycles and proceeded to surgical resection of oligometastatic disease. Through workplace education and upskilling, the proactive management of the side effects including cytokine release syndrome can be managed in the oncology inpatients and seamlessly moved to outpatient settings.