Evaluating PD-1/PD-L1 in Locally Advanced Rectal Cancer by Quantitative Fluorescence Molecular Endoscopy
Colorectal cancer (CRC) claims 10% of global cancer-related deaths annually, with rising incidence. Locally advanced rectal cancer (LARC) requires improved diagnostic techniques. This study focuses on dual-wavelength quantitative fluorescence molecular endoscopy (qFME) using PD-1/PD-L1-targeted tracers for LARC patients undergoing neoadjuvant treatment. Eighteen patients will receive nivolumab-800CW and durvalumab-680LT before qFME procedures, assessing programmed death-1/programmed death ligand-1 (PD-1/PD-L1) expression. We want to test the feasibility of qFME and ex vivo fluorescence imaging after intravenous administration of nivolumab-800CW, targeting PD-1, and durvalumab-680LT, targeting PD-L1, to visualize PD-L1 and PD-1 expression before and after CRT in LARC patients. If successful, this method can potentially be used in the future to see which patients most likely benefit from additional immunotherapy beforehand. The non-randomized, prospective phase 1 intervention explores biomarkers' role in treatment response prediction. Tracer administration poses minimal risks. Patients will not directly benefit, but the study aims to establish the utility of nivolumab-800CW and durvalumab-680LT in determining PD-1/PD-L1 expression during endoscopy.
- EligibilityCriteria: Inclusion Criteria:  Diagnosed with LARC (cT3c-4, N1-2, M0); Written informed consent is obtained; (We aim to include only patients who consent to both study procedures, however if some patients (n<9) do not consent to the first or second procedure or withdraw their consent for the second procedure after the first procedure, they can still be included) Be at least 18 years old; Speak the Dutch language.  Exclusion Criteria:  Concurrent uncontrolled medical conditions according to treating medical physician; Pregnancy or breast feeding. A negative pregnancy test must be available for women of childbearing potential on the day of tracer administration (i.e. premenopausal women with intact reproductive organs and women less than two years after menopause); Prior irradical endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) of the primary tumor. Received an investigational drug within 30 days prior to administration of nivolumab-800CW and durvalumab-680LT according to the patient's medical history; History of infusion reactions to nivolumab, durvalumab or other monoclonal antibodies according to the patient's medical history; Active episode of inflammatory bowel disease; Use of immunosuppressive agents; Medical or psychiatric conditions that compromise the patient's ability to give informed consent according to treating medical physician. - HealthyVolunteers: No - Gender: All - MinimumAge: 18 Years - StdAgeList: Adult, Older Adult