Phase 1a/1b GTB-5550 B7-H3–targeted TriKE NK-cell engager (CD16 + IL-15)

This first-in-human Phase 1a/1b, open-label, non-randomized basket study evaluates GTB-5550, a camelid nanobody tri-specific killer engager (TriKE) designed to activate and expand endogenous NK cells while directing them to B7-H3–expressing tumor cells. Mechanistically, GTB-5550 links (1) an anti-CD16 arm to trigger NK-cell cytotoxicity, (2) a wild-type IL-15 moiety to support NK-cell proliferation/survival, and (3) an anti–B7-H3 arm to target CD276 on tumors—an “in vivo NK engager” alternative to adoptive NK-cell manufacturing. The Phase 1a dose-escalation uses an adaptive BOIN approach across up to six subcutaneous dose levels, followed by Phase 1b expansion across metastatic cohorts including mCRPC, ovarian, breast, head and neck squamous cell carcinoma, NSCLC, pancreatic, and urothelial cancer, generally after ≥2 prior systemic lines (prostate after ≥1 line in the castration-resistant setting). The academic sponsor is Masonic Cancer Center at the University of Minnesota; the TriKE platform and GTB-5550 program are associated with GT Biopharma. Clinically, these populations typically cycle through histology-specific standards—e.g., mCRPC often receives AR-pathway inhibitors, taxane chemotherapy, radioligand therapy when eligible, and PARP inhibitors for select DNA-repair alterations—so this trial tests whether B7-H3–directed NK engagement can add a tumor-agnostic immunotherapy option in heavily pretreated disease.