Safety and effectiveness of SGM-101, a fluorescent antibody targeting carcinoembryonic antigen, for intraoperative detection of colorectal cancer: a dose-escalation pilot study.

摘要: Summary Background Tumour-targeted fluorescence imaging has the potential to advance current practice of oncological surgery by selectively highlighting malignant tissue during surgery. Carcinoembryonic antigen (CEA) is overexpressed in 90% colorectal cancers and a promising target for cancer imaging. We aimed assess tolerability SGM-101, fluorescent anti-CEA monoclonal antibody, investigate feasibility detect with intraoperative Methods did an open-label, pilot study two medical centres Netherlands. In dose-escalation cohort, we included patients (aged ≥18 years) primary increased serum CEA concentrations (upper limit normal ≥3 ng/mL) since diagnosis, who were scheduled open or laparoscopic tumour resection. expansion recurrent peritoneal metastases cancer, increasing surgical not mask patients, investigators, anyone from health-care team. assigned using 3 + 3 dose design 5 mg, 7·5 10 mg SGM-101 cohort. received that was considered optimal at moment but higher than used administered intravenously 30 min 2 4 days before Intraoperative done identify near-infrared lesions, which resected assessed fluorescence. The outcome safety administration continued up 12 h after dosing, on day surgery, first postoperative day, follow-up visits discharge outpatient clinic visit. Secondary outcomes effectiveness detection tumour-to-background ratios (TBR); concordance between signal status tissue; diagnostic accuracy both cohorts. This trial registered Nederlands Trial Register, number NTR5673, ClinicalTrials.gov, NCT02973672. Findings Between January, 2016, February, 2017, 26 (nine cohort 17 cohort) this study. cause any treatment-related adverse events, although three possibly related mild events reported (33%) nine five (18%) Five moderate they deemed unrelated SGM-101. No changes vital signs, electrocardiogram, laboratory results found maximum A showed highest TBR (mean 6·10 [SD 0·42] cohort). 19 (43%) 43 lesions detected clinically suspected detection, changed treatment strategy six (35%) patients. Sensitivity 98%, specificity 62%, intensity 84% Interpretation presents clinical use CEA-targeted shows safe can influence decision making procedure cancer. Funding Surgimab.