Evaluation of SGM-101, a Fluorochrome-Labeled Anti-CEA Monoclonal Antibody, in Locally Advanced or Recurrent Rectal Cancer Undergoing Curative Surgery

The primary objective of this study is to evaluate the clinical benefit of **Fluorescence-Guided Oncologic Surgery (FGOS)** combined with **SGM-101** as an intraoperative imaging agent in patients with locally advanced or recurrent rectal cancer undergoing curative surgery. The corresponding endpoint is the rate of patients achieving R0 resections, which is clinically significant as it indicates complete removal of the tumor with no cancer cells at the resection margins, potentially improving patient outcomes and reducing recurrence rates.

Secondary objectives include:

• Determining the effect of FGOS combined with SGM-101 on intra-operative decision making, assessing changes in surgical plans and post-surgical management, and comparing standard care surgery with FGOS to evaluate the removal of additional malignant lesions and reduction of non-malignant tissue resection.
• Evaluating the performance of SGM-101 in the intra-operative detection of rectal cancer by measuring the tumor-to-background ratio and the concordance between fluorescent signals and histopathologic results.
• Comparing intra-operative fluorescence imaging with SGM-101 to histopathology, focusing on the rates of false negatives, false positives, true negatives, and true positives.
• Assessing changes in surgical planning due to FGOS combined with SGM-101 on 30-day mortality and complication rates to substantiate the benefit/risk assessment of using SGM-101.

The clinical trial involves participants diagnosed with **rectal cancer**, specifically those with a clinical diagnosis of T3 with a threatened circumferential resection margin (CRM) or T4 rectal cancer, as well as recurrent cases. The study population includes both male and female subjects aged over 18 years. Participants are required to practice effective contraception during the study and for at least 30 days following their last dose of the study treatment. The trial does not include a vulnerable population. The sponsor has not provided information regarding the total number of participants. Participants were selected based on their eligibility for surgery and their ability to provide informed consent. No specific lifestyle considerations such as diet or physical activity are mentioned as part of the selection criteria.

The clinical trial is designed to evaluate the performance of **SGM-101**, a fluorochrome-labeled anti-carcinoembryonic antigen monoclonal antibody, in patients with locally advanced or recurrent **rectal cancer** undergoing curative surgery. This is a multicenter, open-label, controlled, parallel arms study. The trial is expected to run from June 2019 to January 2027, with the primary objective being the clinical benefit of using SGM-101 as an intraoperative imaging agent, specifically focusing on the rate of patients achieving R0 resections.

Participants will be randomly assigned to different arms of the study, ensuring a controlled comparison of outcomes. The trial will include several key visits: an initial screening visit to confirm eligibility based on inclusion criteria such as age over 18 years, eligibility for surgery, and the ability to provide informed consent. Follow-up visits will be scheduled to monitor the participants' response to the treatment and any adverse effects. The end-of-study visit will assess the primary and secondary endpoints, including the concordance between intraoperative fluorescence assessment and histopathology, tumor to background ratio, and changes in operative plans due to imaging.

The expected length of participant involvement will vary, but the maximum treatment period for the investigational product is one day, with a maximum total dose of 15 mg administered via intravenous infusion. Participants may be withdrawn from the study early if they experience significant adverse effects, withdraw consent, or if the investigator deems it necessary for their safety. The study will also track secondary endpoints such as 30-day mortality and complication rates, as well as 2-year overall survival and disease-free survival rates.

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** specifically targeting the **carcinoembryonic antigen** (CEA) and is conjugated to the fluorochrome BM-104. This investigational product is administered via **intravenous infusion**. The maximum daily dose is 15 mg, with a total dose not exceeding 15 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. The primary role of SGM-101 in the trial is to serve as an intraoperative imaging agent, enhancing the visualization of cancerous tissues during surgery for locally advanced or recurrent rectal cancer.

In addition to the experimental treatment, the study utilizes a **fluorescence camera system** known as the Quest Spectrum System. This device, which has a CE mark, is employed to capture the fluorescence emitted by the fluorochrome-labeled antibody, thereby aiding in the surgical procedure. The use of this device is integral to the trial's objective of assessing the clinical benefit of fluorescence-guided surgery (FGOS) combined with SGM-101. The endpoint of interest is the rate of patients achieving R0 resections, indicating the complete removal of cancerous tissue.

Participant compliance with the dosing schedule and administration protocol is monitored throughout the trial. The study does not include any non-experimental treatments such as standard-of-care therapy or placebo. The focus remains on evaluating the efficacy and safety of SGM-101 as an imaging agent in the specified patient population.

Efficacy in this clinical trial will be assessed primarily through the rate of patients achieving **R0 resections**, which is the primary endpoint. This endpoint is aligned with the main objective of evaluating the clinical benefit of FGOS combined with SGM-101 as an intraoperative imaging agent in patients with locally advanced or recurrent rectal cancer undergoing curative surgery. The secondary endpoints include several parameters: concordance between intraoperative fluorescence assessment of resected lesions and their histopathology, rates of false negatives, false positives, true negatives, and true positives concerning fluorescence with histopathology as the gold standard, and the tumor to background ratio (TBR) for fluorescence in malignant and benign tissue. Additionally, modifications in the operative plan due to imaging, such as changes in the extent of resection or adjustments in intraoperative radiotherapy (IORT), and subsequent changes in postoperative treatment will be recorded. Other secondary endpoints include 30-day mortality and complication rates, as well as 2-year overall survival, disease-free survival, and local recurrence-free survival.