Delving into the Latest Updates on SGM-101 with Synapse

BACKGROUNDIntraoperative molecular imaging has emerged as a potential tool in addressing challenges faced during lung cancer surgery by localizing small lesions, ensuring negative margins, and identifying synchronous cancers. Carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) glycoprotein has emerged as a potential target in fluorescent labeling of non-small cell lung cancer given the high antigen density in tumor cells and absence of expression in normal parenchyma. The goal of our study was to determine whether anti-CEACAM5 targeted near-infrared fluorochrome could be a suitable target in non-small cell lung cancer.METHODSThe CEACAM5 expression was evaluated in AB-12 (known negative control), HT29 (known positive control), and H460 (non-small cell lung cancer) cell lines by polymerase chain reaction. SGM-101, a CEACAM5 antibody, coupled with a BM-104 near-infrared fluorescent tracer was evaluated with dose escalation, in vitro cellular localization, and immunofluorescence microscopy. Subsequently, in vivo validation was performed in 52 athymic nude xenografts.RESULTSPolymerase chain reaction analysis demonstrated 3000x relative expression of CEACAM5 in HT-29 cells compared with AB-12. The H460 cells showed 1000x relative expression compared with AB12 (P < .05). Both HT29 and H460 cells showed tracer internalization with signal to background ratio of 4.5 (SD 0.34) whereas there was minimal uptake by AB12 cells with signal to background ratio 1.1 (SD 0.1; P < .05). There was linear fluorescence increase with increasing tracer dosing in receptor expressing cell lines. In preclinical models, HT-29 and H460 cells lines produced near-infrared fluorescence with average tumor to background ratio of 3.89 (SD 0.25) irrespective of tumor size compared with no fluorescence by AB12 tumors (P < .05). The CEACAM5 expressing tumors had excellent dye uptake compared with AB12 tumors.CONCLUSIONSCEACAM5 serves as a possible receptor for targeted intraoperative molecular imaging resections in lung cancer. This study sets a path for evaluation of CEACAM5 targets in future clinical trials.

01 Oct 2022·Surgery

Proof of concept of improved fluorescence-guided surgery of colon cancer liver metastasis using color-coded imaging of a tumor-labeling fluorescent antibody and indocyanine green restricted to the adjacent liver segment

Article

Author: Bouvet, Michael ; Framery, Bérénice ; Lwin, Thinzar M ; Cailler, Françoise ; Amirfakhri, Siamak ; Hollandsworth, Hannah M ; Turner, Michael A ; Nishino, Hiroto ; Hoffman, Robert M ; Hosseini, Mojgan ; Pèlegrin, André

BACKGROUNDIndocyanine green has been used for fluorescence-guided surgery of liver metastasis and labeling of liver segments. However, indocyanine green is nonspecific, and indocyanine green labeling does not always clearly outline tumor margins. In addition, it is difficult to distinguish between a tumor and its adjacent liver segment colored with indocyanine green alone. In the present study, we performed fluorescence-guided surgery in an orthotopic colon-cancer liver metastasis mouse model by labeling the metastatic liver tumor with an anti-carcinoembryonic antigen fluorescent antibody and with indocyanine green restricted to the adjacent liver segment.METHODSA liver metastasis model was established with human LS174T colon cancer tumor fragments. To label the tumor, mice received SGM-101, an anti-carcinoembryonic antigen antibody conjugated to a near-infrared fluorophore (700 nm), currently in clinical trials, 3 days before surgery. Indocyanine green (800 nm) was injected after ligation of the tumor-bearing Glissonean pedicle with fluorescence labeling restricted to the liver segment adjacent to the tumor. Bright-light surgery and fluorescence-guided surgery were performed to resect the liver metastasis. To assess recurrence, mice underwent necropsy 3 weeks after surgery and the tumor was weighed.RESULTSFluorescence-guided anatomic left lateral lobectomy and fluorescence-guided partial liver resection were both performed with color-coded double labeled imaging. Tumor weight 3 weeks after surgery was significantly lower with fluorescence-guided surgery compared to bright-light surgery (38 ± 57 mg vs 836 ± 668 mg, P = .011) for partial liver resection.CONCLUSIONThe present study provides a proof-of-concept that color-coded and double labeling of the tumor and adjacent liver segment has the potential to improve liver metastasectomy.

01 Mar 2021·Annals of Surgical OncologyQ2 · MEDICINE

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

Q2 · MEDICINE

Article

Author: van der Valk, Maxime J ; Kamerling, Ingrid M ; Kusters, Miranda ; de Valk, Kim S ; Schaap, Dennis P ; Holman, Fabian A ; Framery, Bérénice ; Vahrmeijer, Alexander L ; Hoogstins, Charlotte E ; Deken, Marion M ; Rutten, Harm J ; Hilling, Denise E ; Burggraaf, Jacobus ; Bhairosingh, Shadhvi S ; Boogerd, Leonora S ; Cailler, Françoise ; Peeters, Koen C ; Meijer, Ruben P

AbstractBackgroundCarcinoembryonic 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.MethodsPatients 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.ResultsThirty-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.ConclusionsThe 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.

100 Deals associated with SGM-101

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Indication	Highest Phase	Country/Location	Organization	Date
Colorectal Cancer	Phase 3	US	SurgiMab SAS	17 Jun 2019
Colorectal Cancer	Phase 3	DE	SurgiMab SAS	17 Jun 2019
Colorectal Cancer	Phase 3	NL	SurgiMab SAS	17 Jun 2019
Colorectal Cancer	Phase 3	IT	SurgiMab SAS	17 Jun 2019
Gastrointestinal polyps	Phase 2	NL	Academisch Ziekenhuis Leiden	31 Jan 2024
Brain metastases	Phase 2	NL	SurgiMab SAS	01 Jan 2024
Rectal Cancer	Phase 2	NL	SurgiMab SAS	01 Jan 2024
Metastatic colon cancer	Discovery	NL	SurgiMab SAS	01 Nov 2020
Secondary malignant neoplasm of lung	Discovery	NL	SurgiMab SAS	01 Nov 2020