89Zr-lumretuzumab PET imaging before and during HER3 antibody lumretuzumab treatment of solid tumor patients.

11555Background: Lumretuzumab is a humanized, glycoengineered, monoclonal antibody targeting human epidermal growth factor receptor 3 (HER3), in phase Ib clinical development in patients with HER3-positive solid tumors. We performed a PET imaging study with 89Zr-lumretuzumab to demonstrate tumor targeting and support dose selection by evaluating the dose required for target saturation. Methods: Thirteen patients with HER3-positive metastatic or locally advanced solid tumors were imaged at baseline with PET 4 and 7 days after receiving 37 MBq 89Zr-lumretuzumab, along with a previously determined imaging protein dose of 100 mg unlabeled lumretuzumab. After 2 weeks, imaging was repeated using the PD-active dose of 400, 800 or 1600 mg unlabeled lumretuzumab combined with 89Zr-lumretuzumab. Normal organ and tumor uptake were calculated as standardized uptake values (SUV). Results: 59 out of 109 lesions (54%) with a size of ≥ 10 mm were quantifiable on baseline PET scans. 39 (36%) showed no visible tracer uptak...