RT Journal Article
SR Electronic
T1 A Phase 1 and Biodistribution Study of ABT-806i, An Indium-111 Radiolabeled Conjugate of the Tumor-Specific Anti-EGFR Antibody ABT-806
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP jnumed.120.253146
DO 10.2967/jnumed.120.253146
A1 Hui K Gan
A1 Matthew Burge
A1 Benjamin Solomon
A1 SzeTing Lee
A1 Kyle D Holen
A1 Yumin Zhang
A1 Marika Ciprotti
A1 FT Lee
A1 Wijth Manusinghe
A1 Judee Fischer
A1 Peter Ansell
A1 Gerard Fox
A1 Hao Xiong
A1 Edward B Reilly
A1 Rod Humerickhouse
A1 Andrew M Scott
YR 2021
UL http://jnm.snmjournals.org/content/early/2021/01/22/jnumed.120.253146.abstract
AB ABT-806 is a tumor-specific antibody targeting the epidermal growth factor receptor (EGFR). This study assessed safety, biodistribution and pharmacokinetics of indium-111 (111In) radiolabeled ABT-806 (ABT-806i) and effects of repeated doses of ABT-806 on receptor occupancy. Methods: Eligible patients had advanced tumors likely to express EGFR/EGFRvIII; adequate performance status and organ function; and measurable disease by RECIST 1.1. In Cohort 1, 6 patients received a bolus administration of ABT-806i and underwent single-photon emission computed tomography (SPECT) followed by whole body planar scans. In Cohort 2, 12 patients were imaged similarly as in 1 initially; thereafter they received three doses of unlabelled ABT-806, before another dose of ABT-806i with associated SPECT and whole body planar scans. At the end of both cohorts, patients who had stable or responding disease were able to enroll into an extension study (M12-326) where they received unlabelled ABT-806 every 2 weeks until disease progression, withdrawal of consent or intolerable toxicity Results: No toxicity related to ABT-806i infusion were observed. ABT-806i showed minimal uptake in normal tissues and cleared gradually from blood with t½ of 6.0 + 1.5 days. The mean effective dose of ABT-806i was determined as 0.137 mSv/MBq for males and 0.183 mSv/MBq for females. ABT-806i tumor uptake varied and did not correlate with archived tumor EGFR expression. No change in ABT-806i uptake was observed after interval ABT-806 treatment, indicating stable EGFR expression in tumor. The patient with highest tumor uptake of ABT-806i had advanced head and neck cancer and experienced a partial response. Conclusion: ABT-806i allows for real-time imaging of EGFR conformational expression in tumors, has an acceptable radiation dosimetry and provides important additional information about antigen expression compared to standard approaches using archival tissue. Its role to assist in patient selection for EGFR-based therapeutics and investigate treatment resistance should be further investigated.