Dose-Finding Study of a CEA-Targeting Agent, SGM-101, for Intraoperative Fluorescence Imaging of Colorectal Cancer
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ORIGINAL ARTICLE – TRANSLATIONAL RESEARCH
Dose-Finding Study of a CEA-Targeting Agent, SGM-101, for Intraoperative Fluorescence Imaging of Colorectal Cancer Kim S. de Valk, MD1,2, Marion M. Deken, MD2, Dennis P. Schaap, BSc3, Ruben P. Meijer, MD1,2, Leonora S. Boogerd, MD, PhD2, Charlotte E. Hoogstins, MD, PhD1,2, Maxime J. van der Valk, MD2, Ingrid M. Kamerling, MD, PhD1, Shadhvi S. Bhairosingh, BSc2, Be´re´nice Framery, MSc4, Denise E. Hilling, MD, PhD2, Koen C. Peeters, MD, PhD2, Fabian A. Holman, MD, PhD2, Miranda Kusters, MD5, Harm J. Rutten, MD, PhD3, Franc¸oise Cailler, PhD4, Jacobus Burggraaf, MD, PhD1, and Alexander L. Vahrmeijer, MD, PhD2 Centre for Human Drug Research, Leiden, The Netherlands; 2Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands; 3Department of Surgery, Catharina Hospital Eindhoven, Eindhoven, The Netherlands; 4 SurgiMab, Montpellier, France; 5Department of Surgery, Amsterdam University Medical Center, Amsterdam, The Netherlands 1
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
Electronic supplementary material The online version of this article (https://doi.org/10.1245/s10434-020-09069-2) contains supplementary material, which is available to authorized users. Ó The Author(s) 2020 First Received: 24 February 2020 Accepted: 9 August 2020 A. L. Vahrmeijer, MD, PhD e-mail: [email protected]
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.
Colorectal cancer (CRC) is one of the most commonly d
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