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).