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

Abstract

Purpose: 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.

Procedures: 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.

Results: 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.

Conclusions: [(64)Cu]DOTA-patritumab was safe. These limited results suggest that this PET-based method can be used to determine tumor-apparent RO.

Trial registration: ClinicalTrials.gov NCT01479023.

Keywords: Dosimetry; Human epidermal growth factor receptor 3; PET/CT; Patritumab; Phase 1; Receptor occupancy; [64Cu]DOTA-patritumab.

Conflict of interest statement

CONFLICT OF INTEREST

Drs. Lockhart, Liu, Dehdashti, Laforest, Welch and Siegel received research support from Daiichi-Sankyo to conduct the preclinical and clinical components of this study. Drs. Desai, Mahmood and Mendell were Daiichi-Sankyo employees at the time that this study was conducted.

Figures

Figure 1

Transaxial lung window (top) CT of the PET/CT demonstrates masses in both lung bases. Transaxial fused PET/CT (second row) and PET (third row) images, and reprojection (bottom) PET images of patient 8 (Receptor Occupancy Cohort) at baseline (Day 2) and after predosing (Day 9) with unlabeled patritumab show greater tracer uptake in the right lung base metastatic colon cancer after unlabeled patritumab, as well as higher blood pool activity and substantially decreased hepatic uptake. The measured apparent receptor occupancy was 41.3%.