Abstract P2-14-07: Use of an activatable cell penetrating peptide-fluorescent imaging agent (AVB-620) to identify positive and close margins intraoperatively

Background: Intra-operative identification of positive margins and lymph nodes continues to be a challenge for breast cancer surgeons. Current techniques such as frozen section or touch prep cytology are time consuming and vary in accuracy across institutions. Our study is the first part of a phase 2 trial of a systemically administered, ratiometric, activatable, cell-penetrating fluorescent peptide dye conjugate that visualizes breast cancer tumor tissue in vivo and ex vivo. We hypothesized that this method would be able to identify breast cancer close to the margin of lumpectomy specimens. Methods: AVB-620 is a cell penetrating peptide-fluorescent imaging agent which undergoes proteolytic cleavage by proteases in the matrix metalloproteinase family that have higher activity in cancerous tissue. After cleavage, the predominant fluorescent emission wavelength changes and fluorescent intensity increases, generating a ratiometric readout. AVB-620 was administered 3- 24 hours prior to operation via intravenous infusion to stage 0-III breast cancer patients. Patients were monitored for safety followed by primary breast surgery and either sentinel lymph node biopsy (SLNB) with radiotracer only or axillary lymph node dissection (ALND). Using a near-infrared camera system, fluorescent intensity of two wavelengths was measured intraoperatively both in vivo and ex vivo, including primary tumors, shave margins, and lymph nodes. The ratio of the intensity of these two wavelengths was utilized to distinguish between malignant and non-malignant tissues and visualized on a video monitor. Pathology reports were correlated to a computer-assisted human review of the fluorescent images. Results: Thirty-two patients were dosed without adverse events attributable to the agent; 31 were evaluable for fluorescent imaging. The average age of patients was 60 years (range 32-79). All patients underwent lumpectomy and axillary surgery. Two patients received neoadjuvant chemotherapy; 10% of patients had pure DCIS tumors. Among invasive tumors: 94% were ER+; 13% were high grade. All primary tumor images demonstrated fluorescent intensity and ratiometric changes that differentiated malignant and non-malignant tissue. 35% of patients had at least one positive margin (invasive tumor on ink or DCIS ≤2mm from ink). 61% of cases had at least one margin that was considered either close (≤2mm from ink for invasive tumor) or positive on HE 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-14-07.