A Phase 1 and Biodistribution Study of ABT-806i, An Indium-111 Radiolabeled Conjugate of the Tumor-Specific Anti-EGFR Antibody ABT-806.

2021-06-01

Gan, Hui K

Burge, Matthew

Solomon, Benjamin

Lee, Sze Ting

Holen, Kyle D

Zhang, Yumin

Ciprotti, Marika

Lee, F T

Manusinghe, Wijth

Fischer, Judee

Ansell, Peter

Fox, Gerard

Xiong, Hao

Reilly, Edward B

Humerickhouse, Rod

Scott, Andrew M

Biodistribution

EGFR

EGFRvIII

Monoclonal Antibodies

Oncology: General

SPECT

SPECT Imaging

Solid Tumors

Journal Article

0000-0001-7319-8546

10.2967/jnumed.120.253146

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.

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Journal of Nuclear Medicine 2021; 62(6): 787-794

Journal of Nuclear Medicine