Evaluation of SGM-101 and Indocyanine Green for Fluorescence-Guided Resection of Colorectal Liver Metastases in Surgical Oncology

The primary objective of this study is to assess the feasibility of the simultaneous use of **Indocyanine Green (ICG)** and **SGM-101** for intraoperative imaging of colorectal liver metastases. This is clinically relevant as it aims to enhance the precision of surgical resections, potentially improving patient outcomes by ensuring more accurate removal of metastatic tissue.

Secondary objectives include:

• Assessing the accuracy of ICG, SGM-101, or both in demonstrating irradical resection at both lesion and patient levels.
• Evaluating the in vivo and ex vivo concordance rate of ICG, SGM-101, or both with the histopathological status of resected lesions, aiming to reduce false positives.
• Determining the in vivo and ex vivo signal-to-background ratios for SGM-101 and ICG.
• Assessing intraoperative changes in surgical plans based on fluorescence and correlating these changes with histopathological outcomes.
• Determining surgeon satisfaction and perceived effectiveness of SGM-101 in addition to ICG.
• Exploring the correlation between fluorescent intensity and tissue carcinoembryonic antigen (CEA) expression.
• Investigating the effect of tumor depth on fluorescent signals for both ICG and SGM-101.
• Evaluating the feasibility of a minimally invasive diagnostic approach for early detection of colorectal cancer through circulating tumor cells (CTCs) and extracellular vesicles (EVs).
• Assessing the feasibility of using CTCs and EVs in the blood of colorectal cancer patients as biomarkers for early detection of recurrence or metastasis.
• Evaluating the feasibility of using CTCs and EVs from peripheral blood for disease monitoring and early cancer detection.

The clinical trial involves participants diagnosed with **colorectal liver metastases**, focusing on the feasibility of using ICG and SGM-101 for intraoperative imaging. The study population includes both male and female subjects, aged 18 years and older. Participants are selected based on their diagnosis of liver metastases of colorectal origin, with surgical resection proposed. The trial includes individuals who are scheduled for surgical resection of more than three colorectal liver metastases, have completed neo-adjuvant therapy within three months before surgery, or are scheduled for surgery due to a locally recurrent liver metastasis. The trial population is considered vulnerable, and participants must be willing and capable of providing informed consent. The sponsor has not provided information regarding the total number of participants or specific lifestyle considerations such as diet or physical activity.

The clinical trial is designed to evaluate the feasibility of using **SGM-101**, a **chimeric monoclonal antibody against carcinoembryonic antigen conjugated to fluorochrome BM-104**, in conjunction with Indocyanine Green (ICG) for intraoperative imaging of colorectal liver metastases. This is a Phase 4, randomized, double-blind, controlled trial. The trial is expected to commence on August 1, 2023, and conclude by December 1, 2024. Participants will be involved in the study for a maximum treatment period of one day, with the primary endpoint being the practical workability and patient experience during surgery, as well as the sensitivity of SGM-101 in detecting lesions.

The study will include several visits, starting with a screening visit to confirm eligibility based on criteria such as being 18 years or older, having a diagnosis of liver metastases of colorectal origin, and being scheduled for surgical resection. Participants must also be willing and capable of providing informed consent. Follow-up visits will be conducted to monitor the accuracy of SGM-101 and ICG in demonstrating irradical resection and to assess the concordance rate with histopathological results. The end-of-study visit will evaluate the overall outcomes, including the modification of operative plans due to imaging and the correlation to histopathology.

Participants may be terminated early from the study if they do not meet the inclusion criteria, withdraw consent, or experience adverse events that compromise their safety. The trial will ensure that no cross-interference of fluorescent signals occurs between the two dyes, and secondary endpoints will include the evaluation of the accuracy of the imaging agents and the feasibility of using circulating tumor cells and extracellular vesicles for early detection and monitoring of colorectal cancer. The study aims to provide valuable insights into the potential of SGM-101 and ICG in enhancing surgical outcomes for patients with colorectal liver metastases.

The clinical trial involves the use of **SGM-101**, an experimental medication formulated as a **solution for injection**. SGM-101 is a **chimeric monoclonal antibody** targeting the **carcinoembryonic antigen** and is conjugated to the fluorochrome BM-104. This pharmaceutical product is administered via **intravenous injection**. The maximum daily dose is 10 mg, with a total dose not exceeding 10 mg over the treatment period, which is limited to a single day. The medication is developed by SURGIMAB S.A.S. and is not designated as an orphan drug nor formulated for pediatric use.

In addition to SGM-101, the study utilizes **Indocyanine Green (ICG)** as a non-experimental treatment. ICG is a standard-of-care imaging agent used for fluorescence-guided surgery. It is administered to enhance the visualization of colorectal liver metastases during surgical procedures. The combination of SGM-101 and ICG aims to assess the feasibility of simultaneous intraoperative imaging, providing enhanced guidance for the resection of metastatic lesions.

The clinical trial aims to assess the efficacy of the investigational product SGM-101, a **chimeric monoclonal antibody against carcinoembryonic antigen conjugated to fluorochrome BM-104**, in the context of fluorescence-guided resection of colorectal liver metastases. The primary endpoints for evaluating efficacy include a positive score on practical workability during surgery and patient experience, both measured through specific surveys. Additionally, the sensitivity of SGM-101 is assessed, requiring at least 80% sensitivity, with specific criteria for capsular and subcapsular lesions based on the tumor-to-background ratio (TBR) in vivo and ex vivo.

Secondary endpoints focus on the accuracy of SGM-101 and Indocyanine Green (ICG) in demonstrating irradical resection, with metrics such as sensitivity, specificity, positive predictive value, and negative predictive value. The concordance rate of these agents with histopathological results is also evaluated. For each lesion, TBR for SGM-101 and signal-to-background ratio (SBR) for ICG are calculated using the Quest open camera and Pearl system. The study further examines the modification of operative plans due to imaging and the correlation to histopathology, as well as the correlation between lesion CEA expression and bread loaf TBR measured with the Pearl system. The trial also explores the feasibility of using circulating tumor cells and extracellular vesicles as biomarkers for early detection and monitoring of colorectal cancer.