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Program Number: B264
Session Name: Poster Session

Are we overtreating our patients? A novel method to determine biologic dosing for anti-EGFR antibodies

Aviva S Mattingly, MD, MS; Hidenori Tanaka, MD; Brandee Brown, BS; Syeda Maria Zaidi, MD; Michael C Topf, MD, MSCI; Eben Rosenthal, MD; Vanderbilt University Medical Center

Background: Anti-EGFR therapeutic antibodies are currently given to patients at the maximum tolerated dose (MTD), which may oversaturate the tumor and therefore contribute to toxicity, unnecessary morbidity, financial burden, and discontinuation of therapy. In fact, in January 2023 the FDA released new guidance that calls for determining the optimal biologic dose (OBD) rather than MTD. The purpose of this study is to identify a method for determining the OBD in a preclinical model prior to human trials.

Methods: Escalating doses of panitumumab (0 ug to 250 ug) were injected to mice bearing FaDu xenografts. Tumor drug concentration and saturation was measured through labeling of panitumumab with IRDye800CW (Pan800). We evaluated the macroscopic drug saturation in the tumor by using near-infrared (NIR) fluorescence and the drug concentration in the tumor using fluorescence intensity of homogenized samples with a standard curve.

Results: Escalating Pan800 dose resulted in increasing mean fluorescence intensity (MFI) macroscopically (0.002 to 3.08 MFI). There was a similar increase in tumor drug concentration when quantified (0 to 9.1 ng drug/mg tumor tissue, Figure 1). On pairwise comparison, there was a saturation level at the 75 ug treatment dose, above which tumor concentration did not significantly increase when compared to the highest group of 250 ug (9.1 ng/mg vs 8.0 ng/mg p=0.16). On microscopic immunofluorescence, panitumumab was limited to the periphery of the tumor at sub-saturating doses, but showed homogenous distribution at doses above 75 ug (Figure 2).

Conclusions: Escalating doses of optically labeled panitumumab did not show a significant increase in drug concentration beyond a threshold dose (75 ug Pan800), which correlated with homogenous drug distribution on a microscopic scale.

Figure 1. Tumor drug concentration (ng drug/mg tumor) in mice tumor samples by treatment dose (0 ug to 250 ug pan800).

Figure 2. Microscopic tumor fluorescence with pan800 (green) and DAPI (blue).

 

 

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