Initial clinical experience of 111In radiolabelled amatuximab in patients with mesothelin-expressing cancers

Objectives Amatuximab (MORAb-009) is a chimeric high-affinity monoclonal IgG1/k antibody targeting mesothelin that is being developed for treatment of mesothelin-expressing cancers. Imaging radiolabeled antibodies provides a non-invasive assessment of drug bio-distribution and may improve dosing strategies. Our objective was to characterize the biodistribution, and dosimetry of 111In amatuximab in mesothelin over-expressing cancer patients.

Methods Between Oct 2011 and Feb 2013, 6 patients (4 with malignant mesothelioma and 2 with pancreatic carcinoma) underwent SPECT/CT imaging following administration of 111In amatuximab. Unlabeled amatuximab, 50 mg was given i.v. to saturate any nonspecific binding and shed antigen. Within six hours, 5 mCi of 111In amatuximab was administered i.v. SPECT/CT images were obtained at 4-hours, 24-hours and 120-168 hours post radiotracer injection.

Results In all patients, tumor to background ratios (TBR) consistently met or exceeded an uptake of 1.2 (range 1.2-62) which is considered the minimum TBR that can be visualized. TBRs were higher in tumors of patients with mesothelioma than for pancreatic carcinoma. Interestingly, two patients with distant metastatic lesions demonstrated strong focal uptake with high TBR. Dosimetry estimates were calculated with the effective dose estimated at 0.15 mSv/MBq. The organ which received the highest absorbed dose was the liver (0.041 mGy/MBq).

Conclusions Radio-labeled amatuximab was generally well-tolerated. SPECT/CT imaging had higher TBR activity in mesothelioma than pancreatic cancer tumors. The dosimetry profile of 111In amatuximab was favorable.