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

Abstract 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 (N = 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, n = 3), medium dose (90 nmol, n = 3), or high dose (171 nmol, n = 6) 1 to 3 hours prior to surgery. Following tumor resection, ex vivo 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, mean BVR (SD) 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 (r≥ 0.86; P < 0.029) in cross-sectional tissue slices and between mean fluorescence intensity and EGFR percent area (r = 0.63; P < 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.