First-in-patient study of OTL78 for intraoperative fluorescence imaging of prostate-specific membrane antigen-positive prostate cancer: a single-arm, phase 2a, feasibility trial

Abstract

Background Targeted real-time imaging during robot-assisted radical prostatectomy provides information on the localisation and extent of prostate cancer. We assessed the safety and feasibility of the prostate-specific membrane antigen (PSMA)-targeted fluorescent tracer OTL78 in patients with prostate cancer.Methods In this single-arm, phase 2a, feasibility trial with an adaptive design was carried out in The Netherlands Cancer Institute, Netherlands. Male patients aged 18 years or older, with PSMA PET-avid prostate cancer with an International Society of Urological Pathology (ISUP) grade group of 2 or more, who were scheduled to undergo robot-assisted radical prostatectomy with or without extended pelvic lymph node dissection were eligible. All patients had a robot-assisted radical prostatectomy using OTL78. Based on timing and dose, patients received a single intravenous infusion of OTL78 (0 center dot 06 mg/kg 1-2 h before surgery [dose cohort 1], 0 center dot 03 mg/kg 1-2 h before surgery [dose cohort 2], or 0 center dot 03 mg/kg 24 h before surgery [dose cohort 3]). The primary outcomes, assessed in all enrolled patients, were safety and pharmacokinetics of OTL78. This study is completed and is registered in the European Trial Database, 2019-002393-31, and the International Clinical Trials Registry Platform, NL8552, and is completed.Findings Between lune 29, 2020, and April 1, 2021, 19 patients were screened for eligibility, 18 of whom were enrolled. The median age was 69 years (IQR 64-70) and median prostate-specific antigen concentration was 15 ng/mL (IQR 9 center dot 3-22 center dot 0). In 16 (89%) of 18 patients, robot-assisted radical prostatectomy was accompanied by an extended pelvic lymph node dissection. Three serious adverse events occurred in one (6%) patient: an infected lymphocele, a urosepsis, and an intraperitoneal haemorrhage. These adverse events were considered unrelated to the administration of OTL78 or intraoperative fluorescence imaging. No patient died, required a dose reduction, or required discontinuation due to drug-related toxicity. The dose-normalised maximum serum concentration (Cmax/dose) in patients was 84 center dot 1 ng/mL/mg for the 0 center dot 03 mg/kg dose and 79 center dot 6 ng/mL/mg for the 0 center dot 06 mg/kg dose, the half-life was 5 center dot 1 h for the 0 center dot 03 mg/kg dose and 4 center dot 7 h for the 0 center dot 06 mg/kg dose, the volume of distribution was 22 center dot 9 L for the 0 center dot 03 mg/kg dose and 19 center dot 5 L for the 0 center dot 06 mg/kg dose, and the clearance was 3 center dot 1 L/h for the 0 center dot 03 mg/kg dose and 3 center dot 0 L/h for the 0 center dot 06 mg/kg dose.Interpretation This first-in-patient study showed that OTL78 was well tolerated and had the potential to improve prostate cancer detection. Optimal dosing was 0 center dot 03 mg/kg, 24 h preoperatively. PSMA-directed fluorescence imaging allowed real-time identification of visually occult prostate cancer and might help to achieve complete oncological resections.Funding On Target Laboratories.