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Clinical Trial
. 2021 Mar;28(3):1832-1844.
doi: 10.1245/s10434-020-09069-2. Epub 2020 Oct 9.

Dose-Finding Study of a CEA-Targeting Agent, SGM-101, for Intraoperative Fluorescence Imaging of Colorectal Cancer

Kim S de Valk  1   2 , Marion M Deken  2 , Dennis P Schaap  3 , Ruben P Meijer  1   2 , Leonora S Boogerd  2 , Charlotte E Hoogstins  1   2 , Maxime J van der Valk  2 , Ingrid M Kamerling  1 , Shadhvi S Bhairosingh  2 , Bérénice Framery  4 , Denise E Hilling  2 , Koen C Peeters  2 , Fabian A Holman  2 , Miranda Kusters  5 , Harm J Rutten  3 , Françoise Cailler  4 , Jacobus Burggraaf  1 , Alexander L Vahrmeijer  6
Affiliations
Clinical Trial

Dose-Finding Study of a CEA-Targeting Agent, SGM-101, for Intraoperative Fluorescence Imaging of Colorectal Cancer

Kim S de Valk et al. Ann Surg Oncol. 2021 Mar.

Abstract

Background: Carcinoembryonic antigen is overexpressed in colorectal cancer (CRC), making it an optimal target for fluorescence imaging. A phase I/II study was designed to determine the optimal imaging dose of SGM-101 for intraoperative fluorescence imaging of primary and recurrent CRC.

Methods: Patients were included and received a single dose of SGM-101 at least 24 h before surgery. Patients who received routine anticancer therapy (i.e., radiotherapy or chemotherapy) also were eligible. A dedicated near-infrared imaging system was used for real-time fluorescence imaging during surgery. Safety assessments were performed and SGM-101 efficacy was evaluated per dose level to determine the most optimal imaging dose.

Results: Thirty-seven patients with CRC were included in the analysis. Fluorescence was visible in all primary and recurrent tumors. In seven patients, no fluorescence was seen; all were confirmed as pathological complete responses after neoadjuvant therapy. Two tumors showed false-positive fluorescence. In the 37 patients, a total of 97 lesions were excised. The highest mean intraoperative tumor-to-background ratio (TBR) of 1.9 (p = 0.019) was seen in the 10-mg dose. This dose showed a sensitivity of 96%, specificity of 63%, and negative predictive value of 94%. Nine patients (24%) had a surgical plan alteration based on fluorescence, with additional malignant lesions detected in six patients.

Conclusions: The optimal imaging dose was established at 10 mg 4 days before surgery. The results accentuate the potential of SGM-101 and designated a promising base for the multinational phase III study, which enrolled the first patients in June 2019.

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Figures

Fig. 1
Fig. 1
Flow diagram showing the patient inclusion for this study
Fig. 2
Fig. 2
Example of a true positive and a true negative colorectal carcinoma. A Intraoperative fluorescence of a palpable colorectal tumor during surgery, with a TBR of 2.0 (true positive). B Absence of fluorescence in a tumor, which was confirmed as a pathological complete response by histopathology (true negative). TBR tumor-to-background ratio, NIR near-infrared
Fig. 3
Fig. 3
Intraoperative tumor-to-background ratio (TBR) per dose level. Median and range of the intraoperative TBRs. Note: The dosing-surgery interval time varies within the different dose levels
See this image and copyright information in PMC

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