SAT471 Hearing-Related Adverse Events in Teprotumumab Oncology Clinical Trials

Disclosure: T.J. Smith: Consulting Fee; Self; Horizon Therapeutics plc, Viridian, Lundbeck. Other; Self; US patents covering the use of IGF-1 receptor inhibitors in TED which are held by UCLA and the Lundquist Institute. Q. Fu: Employee; Self; Horizon Therapeutics plc. Stock Owner; Self; Horizon Therapeutics plc. R.J. Holt: Employee; Self; Horizon Therapeutics plc. Stock Owner; Self; Horizon Therapeutics plc. Background: Teprotumumab was originally developed for the treatment of a variety of cancers; however, the development program was terminated due to lack of efficacy although no major safety concerns were observed. Teprotumumab was eventually approved by the FDA for the treatment of thyroid eye disease (TED). Hearing-related adverse events (AEs) with insulin-like growth factor-I receptor inhibitors have been reported in clinical trials. Methods: The incidence and severity of hearing-related AEs, as classified by the Medical Dictionary for Regulatory Activities, in teprotumumab-treated patients (N=633) receiving monotherapy (N=362) or in combination with anti-neoplastic therapy (N=271) from oncology clinical trials was evaluated. The relation of events to teprotumumab, severity, and drug exposure up to time of each event was calculated. Results: A total of 8 oncology clinical trials were included with 8.1% (N=51) of patients reporting any Ear and Labyrinth Disorder AEs, and 2.1 % (N=13) reporting events considered teprotumumab-related by the investigators. 3.8% of patients (N=24) reported hearing impairment or tinnitus-related events with 1.3% (N=8) ascribed to teprotumumab. Approximately 80% of reported AEs were considered mild, with Ear Discomfort being the most common. More than half of AEs were reported within 60 days of therapy initiation. The majority of patients (74%) had teprotumumab exposures consistent with the current FDA-recommended dosing regimen of teprotumumab for TED (150 mg/kg). Findings were consistent regardless of relatedness to teprotumumab or whether given as monotherapy or in combination with anti-neoplastic agents (some of which have been reported to cause hearing-related events). Of the teprotumumab-ascribed hearing AEs, two were considered moderate (deafness and hypoacusis) and one as severe (bilateral deafness). The moderate hypoacusis event occurred in a patient exposed to nearly twice the total dose of the recommended regimen of teprotumumab for TED. The severe event occurred in a patient exposed to almost 7 times the expected exposure with the recommended TED dosing. Conclusions: Hearing-related AE type and incidence were similar in patients who received teprotumumab as monotherapy or in combination with other agents in this sizeable oncology trial program. The most severe events reported were at higher drug exposures than used in the TED clinical trials. The types of AEs and incidence were also comparable to those reported in the TED clinical trial program and as reported in the current FDA-approved prescribed labeling for teprotumumab in the United States. Presentation Date: Saturday, June 17, 2023