Phase 1 Evaluation of [64Cu]DOTA-Patritumab to Assess Dosimetry, Apparent Receptor Occupancy, and Safety in Subjects with Advanced Solid Tumors

The purpose of this study was to evaluate the safety, dosimetry, and apparent receptor occupancy (RO) of [(64)Cu]DOTA-patritumab, a radiolabeled monoclonal antibody directed against HER3/ERBB3 in subjects with advanced solid tumors.Dosimetry subjects (n = 5) received [(64)Cu]DOTA-patritumab and underwent positron emission tomography (PET)/X-ray computed tomography (CT) at 3, 24, and 48 h. Evaluable RO subjects (n = 3 out of 6) received [(64)Cu]DOTA-patritumab at day 1 and day 8 (after 9.0 mg/kg patritumab) followed by PET/CT at 24 h post-injection. Endpoints included safety, tumor uptake, and efficacy.The tumor SUVmax (± SD) was 5.6 ± 4.5, 3.3 ± 1.7, and 3.0 ± 1.1 at 3, 24, and 48 h in dosimetry subjects. The effective dose and critical organ dose (liver) averaged 0.044 ± 0.008 mSv/MBq and 0.46 ± 0.086 mGy/MBq, respectively. In RO subjects, tumor-to-blood ratio decreased from 1.00 ± 0.32 at baseline to 0.57 ± 0.17 after stable patritumab, corresponding to a RO of 42.1 ± 3.[(64)Cu]DOTA-patritumab was safe. These limited results suggest that this PET-based method can be used to determine tumor-apparent RO.