Intraoperative nerve-specific fluorescence visualization in head and neck surgery: a Phase 1 trial

Iatrogenic nerve injury is a surgical complication with significant morbidity. This clinical trial, now complete, investigates the systemic administration of bevonescein, which selectively binds to nerves, in a single-arm, prospective multi-center, dose-escalation Phase 1 trial in adult patients with head and neck neoplasms undergoing parotidectomy or thyroidectomy in the United States. Twenty-seven participants are enrolled in the trial and receive the systemic agent. The primary outcome is safety with no dose-limiting toxicity among the 27 patients, but a single adverse event was identified that was possibly related to the study drug (vomiting). Secondary outcomes include the pharmacokinetics, optimal dose, and timing of bevonescein. The half-life of bevonescein is 29–72 min, and the optimal dose is 500 mg by objective measures, with the fluorescence signal-to-background ratio (SBR; 2.1 ± 0.8) significantly higher compared to white light (1.3 ± 0.2; p = 0.003). The fluorescent SBR of nerves between the early (1–3 h) versus late (3–5 h) timing cohorts is not statistically different. Here, we present data of a nerve imaging agent showing that preoperative intravenous infusion of bevonescein is well tolerated. This trial is registered at ClinicalTrials.gov (NCT04420689) and is sponsored by Alume Biosciences (San Diego, CA). Surgical nerve injuries can cause significant morbidity, yet no approved fluorescent agents exist for visualization. Here, the authors show in a Phase I multi-site trial that bevonescein was safe, established optimal dosing and timing, and provided a fluorescence signal for intraoperative nerve identification.