TY - JOUR
T1 - Image-guided surgery for tumor agnostic detection of solid tumors using the pH-activated micellar imaging agent ONM-100.
AU - Voskuil, Floris Jan
AU - Steinkamp, Pieter Jan
AU - Koller, Marjory
AU - van der Vegt, Bert
AU - Doff, Jan Johannes
AU - Zhao, Tian
AU - Hartung, Jeffrey P.
AU - Jayalakshmi, Yalia
AU - Sumer, Baran D.
AU - Gao, Jinming
AU - Witjes, Max J.H.
AU - Van Dam, Gooitzen Michell
PY - 2019/5/20
Y1 - 2019/5/20
N2 - 3068Background: ONM-100, a micelle-based polymer imaging agent conjugated to indocyanine green (ICG) and with an exquisitely pH-sensitive binary activation mechanism, may be used for tumor detection. ONM-100 micelles dissociate in acidic environments resulting in activation of the fluorescent ICG tag. As nearly all solid cancer types are acidotic, ONM-100 has the potential to act as a broadly indicated tumor agnostic imaging agent. 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). 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 fluorescence images were collected before and after tumor excision. Post-excision fluorescence images were obtained from serially sliced specimens and correlated with standard histopathological assessment. Results: 30 patients (11 BC, 13 HNSCC, 3 EC, 3 CRC) were enrolled. No ONM-100 related serious adverse events were observed and the agent was well-tolerated. A strong and sharply demarcated fluorescent signal was observed in all patients with vital tumor tissue (median CNR ranging 1.85-14.05) which correlated with tumor on final histopathology. HNSCC and superficially located BC as well as peritoneal metastasis could be clearly visualized in vivo during surgery. In four patients (BC and HNSCC), perioperatively, tumors otherwise unnoticed by the surgeons were detected on the margin or wound bed using fluorescence imaging. Additionally, two BC tumor lesions were detected that were missed by conventional pre-operative imaging and pathological assessment. Conclusions: ONM-100 appears to be safe and enables fluorescent visualization of tumors both in vivo and ex vivo. The first-in-human data demonstrate the feasibility for potential use of ONM-100 for image guided surgery, margin assessment and detection of occult disease. Clinical trial information: NTR 7085.
AB - 3068Background: ONM-100, a micelle-based polymer imaging agent conjugated to indocyanine green (ICG) and with an exquisitely pH-sensitive binary activation mechanism, may be used for tumor detection. ONM-100 micelles dissociate in acidic environments resulting in activation of the fluorescent ICG tag. As nearly all solid cancer types are acidotic, ONM-100 has the potential to act as a broadly indicated tumor agnostic imaging agent. 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). 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 fluorescence images were collected before and after tumor excision. Post-excision fluorescence images were obtained from serially sliced specimens and correlated with standard histopathological assessment. Results: 30 patients (11 BC, 13 HNSCC, 3 EC, 3 CRC) were enrolled. No ONM-100 related serious adverse events were observed and the agent was well-tolerated. A strong and sharply demarcated fluorescent signal was observed in all patients with vital tumor tissue (median CNR ranging 1.85-14.05) which correlated with tumor on final histopathology. HNSCC and superficially located BC as well as peritoneal metastasis could be clearly visualized in vivo during surgery. In four patients (BC and HNSCC), perioperatively, tumors otherwise unnoticed by the surgeons were detected on the margin or wound bed using fluorescence imaging. Additionally, two BC tumor lesions were detected that were missed by conventional pre-operative imaging and pathological assessment. Conclusions: ONM-100 appears to be safe and enables fluorescent visualization of tumors both in vivo and ex vivo. The first-in-human data demonstrate the feasibility for potential use of ONM-100 for image guided surgery, margin assessment and detection of occult disease. Clinical trial information: NTR 7085.
U2 - 10.1200/jco.2019.37.15_suppl.3068
DO - 10.1200/jco.2019.37.15_suppl.3068
M3 - Meeting Abstract
VL - 37
SP - 3068
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
SN - 0732-183X
IS - 15_suppl
ER -