Zeta-BC-003 (p21-pathway intratumoral biomaterial) drives CT/MRI lytic defect shrinkage and 0 SREs in MBC bone mets

Zeta-BC-003 is a first-in-class intratumoral injectable biomaterial infused with N-allyl noroxymorphone, designed to activate the p21 pathway to promote bone healing alongside local tumor control. In the open-label ZGMBC Phase 2a trial (NCT05280067), 10 women with metastatic breast cancer (HR+ n=6; HR+/HER2+ n=2; HER2+/HR− n=1; TNBC n=1) and lytic spine lesions (11 treated lesions; SINS 3–9) received a single fluoroscopy-guided intratumoral injection, with CT/MRI at baseline, Day 84, and Day 180: 0 SREs/fractures were reported, mean lytic defect volume fell 65.4% at Day 84 and 84.1% at Day 180 (p=0.0003 and p<0.0001), and all lesions were reported as complete responses; 4 adjacent untreated lesions also showed “therapeutic effect.” No treatment-emergent AEs/SAEs were reported—contrasting with the ongoing residual SRE risk even on bone-modifying agents (e.g., denosumab vs zoledronic acid delays SREs but does not eliminate them; HR 0.82 for time to first on-study SRE), and with real-world/noninferiority datasets where substantial fractions still experience SREs despite bisphosphonates.