Abstract PS1-13-18: Single Intratumoral Drug Injection Yields Complete Response (CR) in Metastatic Breast Cancer (MBC) Bone Lesions: Results from a Phase 2a Trial

Abstract Background: MBC bone defects occur in the axial skeleton in 70% of patients (pts), decreasing survival and quality of life (QoL). Pathologic fracture and spinal cord compression are skeletal-related events (SRE) that further reduce survival. MBC bone lesions create destructive lytic defects that produce debilitating pain often requiring opioid pain management, palliative radiation therapy, and surgery. Reducing SRE risk will improve QoL. Zeta-BC-003, is a first-in-class intratumoral injectable drug therapy that contains a specific concentration of a well-known small molecule, that works via a new molecular pathway. Zeta-BC-003 is comprised of a collagen-calcium phosphate biomaterial infused with N-allyl noroxymorphone resulting in CR in 6 consecutive pts in a Phase 2a trial, consistent with 2 pts previously treated via Compassionate Use (CU) with 2-yr follow-up (Palma et al. Pain Manag, 2023). Methods: ZGMBC (NCT05280067) is a non-randomized, open label Phase 2a trial currently at the University of British Columbia. Ten female pts were enrolled (8/23-3/25) with spinal MBC lytic bone lesions and a Spinal Instability Neoplastic Scale (SINS) score ≥3 and ≤9. Under sedation, 1 lesion per patient was treated with a single intratumoral injection of Zeta-BC-003, via an 18-gauge spinal needle and fluoroscopic guidance. Pts were followed with CT and MRI at discharge and days 84 & 180. Primary endpoints: SREs, Bone defect size change; Pain measured using the Numeric Rating Scale (NRS); and Postoperative prescription opioid use. Secondary endpoints: QoL via SF-12v2, SINS, and treatment response via the MD Anderson Criteria (MDAc) and RECIST v1.1. Results: Pts had a mean age of 52-yrs (range: 32.5 - 67.4) and 9 were pre/peri-menopausal. Six pts had HR+ tumors while 2 were HR+/HER2+, 1 was HER2+/HR-, and 1 was TNBC. Four pts had non-surgically accessible bone MBC (ribs, ilium, skull), 3 had liver metastases (mets), 1 had lung mets, and 3 had mediastinal lymph node mets. Five pts were given bisphosphonates. In the 6 pts that have completed the study there were no SAEs, AEs, or SREs. There were 6 treated lesions for the 6 pts, with one patient having 3 additional adjacent lesions for a total of 9. The mean bone defect volume decreased 87.9% (±8.5%) at day 180. Seven of the MBC bone defects were healed, resulting in normal bone morphology by imaging. All 6 pts had a CR treatment response via the MDAc, which is defined as ‘fill-in’ of the bone defect via CT + no active tumor (‘hot spots’) on MRI. A 24.2% increase in the Physical Component Summary (PCS) and a 12.1% increase in the Mental Component Summary (MCS) showed improved QoL (SF-12v2). Pain decreased 4.16% per the mean NRS. The Morphine Equivalent Dose (MED) was calculated for the 3 pts treated with opioids, which showed a decrease of 66.9%, 66.7%, and 33.3%. QoL improved with decreased MED, with PCS increasing for those pts 36.7%, 13.4%, and 58.4%. Decreased MED related to a lower MCS for 2 pts (2.4% & 6.9%) while the third increased 47.1%. The mean SINS increased 18.5%, from 4.5 to 3.7, indicating increased stability. Conclusion: There were no SREs and Zeta-BC-003 provided a CR (no active tumor) in all 6 pts for all 9 lesions, decreased MBC bone defect volume, increased stability (SINS), decreased pain (NRS & MED), and increased patient QoL. Zeta-BC-003 prevented SREs while 53% of MBC pts with bone mets reported an SRE (Parkes et al. Oncologist 2018). These data are consistent with the pts treated via CU and followed for 2-yrs, in which a CR was observed in all 7 treated MBC bone lesions coupled with decreased pain via the NRS (50%) and 76% less opioid drug use via the MED (day 0: 250-mg vs 2-yrs: 60-mg). These results offer the first non-palliative intratumoral treatment that ceases MBC lytic lesion activity, regrows bone, reduces SRE risk, while increasing QoL and possibly overall survival. Citation Format: M. K. S. Heran, B. S. Margulies, J. C. Loy, D. Villa. Single Intratumoral Drug Injection Yields Complete Response (CR) in Metastatic Breast Cancer (MBC) Bone Lesions: Results from a Phase 2a Trial [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS1-13-18.