Data from First-in-Human Study of ABY-029, a Novel Fluorescent Peptide that Targets EGFR, Applied to Soft-Tissue Sarcomas

<div>Abstract<p>ABY-029, an anti-EGFR Affibody molecule conjugated to IRDye 800CW, recently underwent first-in-human testing in soft-tissue sarcoma. The FDA Exploratory Investigational New Drug status was obtained for the phase 0 clinical trial in which study objectives were to determine whether a biological variance ratio (BVR) of 10 was achievable, whether fluorescence intensity correlated with EGFR expression, and whether doses were well tolerated. Patients (<i>N</i> = 12) with soft-tissue sarcoma were recruited based on positive EGFR IHC staining of diagnostic biopsies. ABY-029 was administered at a microdose (30 nmol, <i>n</i> = 3), medium dose (90 nmol, <i>n</i> = 3), or high dose (171 nmol, <i>n</i> = 6) 1 to 3 hours prior to surgery. Following tumor resection, <i>ex vivo</i> tissue was imaged to determine the mean fluorescence intensity, BVR, and other contrast measures. EGFR expression was correlated with IHC. For micro, medium, and high doses, <i>mean</i> BVR (<i>SD</i>) values in cross-sectional slices were 4 (4), 10 (6), and 7 (8) for the whole tumor region and 6 (5), 13 (11), and 8 (6) for pathology-confirmed regions of interest, respectively. Strong linear correlations were found between all ABY-029 contrast metrics and total EGFR (<i>r</i><math><mrow><mo>≥</mo></mrow></math> 0.86; <i>P</i> < 0.029) in cross-sectional tissue slices and between mean fluorescence intensity and EGFR percent area (<i>r</i> = 0.63; <i>P</i> < 0.0001) in excised region-of-interest tissue sections. No ABY-029–related adverse events were observed. When administered above the microdose, ABY-029 demonstrated a high correlation with EGFR expression and contrast values that were encouraging for translation to clinical practice. Contrast values were similar to those observed with antibody agents but with a substantially reduced imaging-to-resection time and no drug-related adverse events.</p></div>