Phase 1b DCSZ11 CD93-directed monoclonal antibody adds tumor-vasculature immunotherapy to TNT.

This Johns Hopkins–led Phase 1b, open-label total neoadjuvant therapy study evaluates safety and preliminary activity of DCSZ11 (a CD93-directed monoclonal antibody) combined with short-course radiation plus CAPOX (capecitabine + oxaliplatin) for high-risk, mismatch repair–proficient/microsatellite-stable locally advanced rectal adenocarcinoma. The intent is to see whether CD93 blockade—aimed at modulating abnormal tumor vasculature and the tumor microenvironment—can improve response depth and increase complete clinical/pathologic responses when layered onto standard rectal TNT elements. Capecitabine is a fluoropyrimidine that inhibits thymidylate synthase (DNA synthesis), and oxaliplatin is a platinum chemotherapy that forms DNA crosslinks. The scientific angle is bringing a vascular/microenvironment target (CD93) earlier in disease, when immune- and radiation-mediated effects may be more leverageable than in refractory metastatic settings. Today’s care for high-risk pMMR LARC is total neoadjuvant therapy with pelvic radiation (often short-course or long-course chemoradiation) plus multi-agent chemotherapy such as CAPOX or FOLFOX, followed by surgery or, for select responders, nonoperative management.