Abstract CT018: Image guided surgery for tumor agnostic detection of solid tumors using the pH activated micellar imaging agent ONM-100: The Shine study
Authors: Steinkamp Pieter J. , Voskuil Floris J. , Koller Marjory , Vegt Bert van der , Doff Jan J. , Zhao Tian , Hartung Jeffrey P. , Jayalakshmi Yalia , Sumer Baran D. , Gao Jinming , Witjes Max J. , Dam Gooitzen M. van 
Published: August 2019

Abstract
Introduction: ONM-100, an indocyanine green (ICG) conjugated, micelle-based polymer imaging agent with an exquisitely pH-sensitive binary activation mechanism, may be used for intra-operative tumor detection. Micelles dissociate in acidic environments resulting in fluorescent activation of ICG. As most solid cancer types are acidotic due to anaerobic glycolysis, the so-called Warburg effect, ONM-100 has the potential to act as a tumor agnostic imaging agent targeting a broad range of tumors. This first in-human study investigates the safety and feasibility of ONM-100 as a tumor agnostic imaging agent for intra-operative fluorescent imaging of various solid tumors.
Methods: ONM-100 was IV administered 24±8h prior to surgery in a dose escalation scheme (0.1-1.2mg/kg), and the optimal dose was further evaluated in a subsequent cohort. Patients with histopathologically confirmed breast cancer (BC), head and neck squamous cell carcinoma (HNSCC), colorectal cancer (CRC) and esophageal cancer (EC) were included. Blood was drawn to assess safety and pharmacokinetic data. Intra-operative images were collected before and after tumor excision. After excision, fluorescence images were obtained from serially sliced specimens and formalin fixated paraffin embedded tissue blocks and correlated with standard histopathological assessment.
Results: 30 patients (11 BC, 13 HNSCC, 3 EC, 3 CRC) were enrolled between March and December 2018. No ONM-100 related serious adverse events were observed and the agent was well tolerated at all the dose levels. A strong and sharply demarcated fluorescent signal was observed in all patients with vital tumor tissue (median Contrast to Noise Ratio 3.5; IQR 3.4) which correlated with tumor on final histopathology.
Pharmacokinetics showed increased tumor fluorescence in a dose and plasma concentration-dependent manner. HNSCC, superficially located BC, extraluminal CRC as well as peritoneal metastasis could be clearly visualized in vivo during surgery. In 4 patients (BC and HNSCC), perioperatively, an otherwise unnoticed tumor by the surgeon was detected on the margin or wound bed using fluorescence imaging. Additionally, 2 BC tumor lesions were detected which were missed by conventional pre-operative imaging and pathological assessment.
Conclusion: ONM-100 appears to be safe and allows fluorescent visualization of tumors both in- and ex vivo. The first in-human data demonstrates feasibility for potential use of ONM-100 for image guided surgery, detection of occult disease and margin assessment. Analysis of the microscopic biodistribution of ONM-100 is currently being performed and applications for metastatic lymph node detection will be explored.
Note: This abstract was not presented at the meeting.
Citation Format: Pieter J. Steinkamp, Floris J. Voskuil, Marjory Koller, Bert van der Vegt, Jan J. Doff, Tian Zhao, Jeffrey P. Hartung, Yalia Jayalakshmi, Baran D. Sumer, Jinming Gao, Max J. Witjes, Gooitzen M. van Dam. Image guided surgery for tumor agnostic detection of solid tumors using the pH activated micellar imaging agent ONM-100: The Shine study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr CT018.