Biodistribution and dosimetry results from a phase 1 trial of therapy with the antibody-Radionuclide conjugate 177Lu-Lilotomab satetraxetan

Abstract

177Lu-lilotomab satetraxetan is a novel antibody radionuclide conjugate (ARC) currently in a phase 1/2a first-in-human dosage escalation trial for patients with relapsed CD37+ indolent non Hodgkin lymphoma (NHL). The aim of this study was to investigate biodistribution and absorbed doses to organs at risk. Methods: A total of seven patients treated with 177Lu-lilotomab satetraxetan were included for dosimetry. Patients were grouped based on two different pre-dosing regimens (with and without pre-dosing with 40 mg lilotomab) and were treated with different levels of activity per body weight (10, 15 and 20 MBq/kg). All patients were pre-treated with rituximab. Serial planar and SPECT/CT-images were used to determine time activity curves and patient specific masses for organs with 177Lu-lilotomab satetraxetan uptake. Doses were calculated with OLINDA/EXM. Results: Organs with distinct uptake of 177Lu-lilotomab satetraxetan, in addition to red bone marrow and tumors, were liver, spleen and kidneys. Largest uptake was found in the spleen, where doses ranged from 1.54 to 3.60 mGy/MBq. The liver received 0.70 to 1.15 mGy/MBq. The kidneys received the lowest dose of the source organs investigated; 0.16 to 0.79 mGy/MBq. No statistical significant differences in soft tissue absorbed doses for the two pre-dosing regimens were found. Whole body (WB) dose ranged from 0.08 to 0.17 mGy/MBq. Conclusion: The biodistribution study for patients treated with 177Lu-lilotomab satetraxetan revealed highest physiological uptake in liver and spleen, besides red marrow. For all dosage levels investigated, doses were found modest when compared to commonly assumed tolerance limits.