Zetagen Therapeutics Announces Presentation of Promising Phase 2a Data Demonstrating Complete Responses in Metastatic Breast Cancer Bone Lesions at 2025 SABCS
Zetagen Therapeutics, a privately held clinical-stage biopharmaceutical company developing innovative, targeted therapies for both primary and metastatic breast cancer, announced that new clinical results from its Phase 2a study evaluating its lead therapeutic candidate, ZetaMet™ (Zeta-BC-003), have been accepted for presentation at the 2025 San Antonio Breast Cancer Symposium (SABCS). The abstract, titled “Single Intratumoral Drug Injection Yields Complete Response (CR) in Metastatic Breast Cancer (MBC) Bone Lesions,” will be presented in a poster session on Wednesday, December 10, 2025.
The data included in the abstract reflect preliminary findings from a clinical trial exploring the ability of ZetaMet™ to safely and effectively treat metastatic breast cancer (MBC) that has spread to the bone—a complication that affects the majority of patients with advanced disease. The presentation at SABCS 2025 marks an important milestone for the company, as it provides the most comprehensive public disclosure to date of clinical outcomes associated with ZetaMet™, a novel local-treatment drug designed to suppress tumor activity within bone and potentially restore structural integrity.
Background: Unmet Need in Bone Metastatic Breast Cancer
Bone is the most common site for metastasis in breast cancer, with approximately 65–75% of patients diagnosed with Stage 4 disease developing skeletal involvement. Metastatic bone disease contributes to significant patient morbidity, including severe pain, fractures, and impaired mobility, all of which reduce quality of life. A major complication of metastatic bone lesions is the occurrence of skeletal-related events (SREs), including spinal cord compression and pathological fractures, contributing to poorer survival outcomes and increasing healthcare burden.
Despite advances in systemic treatments—including chemotherapy, hormonal therapies, targeted agents, and immunotherapies—there remains no definitive therapy capable of reliably eliminating bone lesions or repairing structural damage. Current standard of care typically relies on radiation therapy, anti-resorptive drugs such as bisphosphonates or RANK-ligand inhibitors, and analgesic management. These approaches are often palliative rather than curative, leaving a significant unmet clinical need.
ZetaMet™ aims to address this gap with a new approach. The therapy is administered through a single, localized intratumoral injection, directly targeting lytic bone lesions and aggressively disrupting tumor growth while allowing patients to avoid systemic toxicities associated with traditional cancer treatments.
Overview of Phase 2a Clinical Study
The preliminary clinical data presented in the SABCS abstract are derived from a recently completed Phase 2a study (NCT05280067) conducted at the University of British Columbia. The trial was designed to assess the safety, feasibility, and initial efficacy of ZetaMet™ in Stage 4 breast cancer patients who had developed lytic bone metastases, meaning lesions in which destructive cancer activity has eroded bone tissue.
The Phase 2a trial enrolled patients across different metastatic breast cancer phenotypes, including:
- Triple-negative breast cancer (TNBC)
- Hormone receptor-positive (HR+)
- HR+/HER2+
- HER2+/HR-
These diverse representations highlight the potential broad applicability of ZetaMet™ across multiple biologically distinct forms of breast cancer.
Each participant received a single injection of ZetaMet™ directly into an identified bone lesion. This procedure was conducted under sedation and guided by fluoroscopy to ensure precise intra-lesional delivery. Notably, the intent was to evaluate whether a single localized intervention could meaningfully suppress tumor activity, reduce clinical risk of SREs, and enhance local bone health.
Key Findings: Complete Response in All Treated Patients
According to the abstract submitted to SABCS, all treated patients achieved a complete response (CR) in their injected bone lesions. Complete response was defined as the absence of detectable tumor activity within the treated areas, as assessed by imaging and clinical follow-up.
Highlights include:
- Complete response in all patients and all treated bone lesions
- No serious adverse events (SAEs) or adverse events (AEs)
- No skeletal-related events (SREs) observed
- Observed reconstitution of trabecular bone structure in many patients
Of particular significance, many patients demonstrated radiographic signs of bone regeneration. Reconstitution of trabecular bone—porous tissue that provides foundational bone strength—suggests that ZetaMet™ may not only eliminate tumor cells but also promote restorative bone health. This dual effect could potentially prevent fractures and improve long-term functional outcomes, an important consideration in metastatic care.
Moreover, the study reported that adjacent untreated lesions within the same vertebral body also demonstrated signs of response, raising potentially important questions about the drug’s mechanism and whether localized delivery may prompt broader therapeutic effects within surrounding bone tissues.
The absence of adverse events, especially skeletal-related complications, underscores the potential safety profile of ZetaMet™, particularly when compared with systemic therapies that often carry significant toxicities.
A Platform Built on Earlier Compassionate Use Success
These Phase 2a results build upon previously reported compassionate-use experiences, which have been published in peer-reviewed medical journals and include up to two-year patient follow-up. Earlier cases similarly documented complete responses and durable remission in treated lesions, suggesting that ZetaMet™ may offer both immediate and long-term benefit.
According to the Zetagen company, the emerging clinical picture strengthens the case that ZetaMet™ has the potential to delay or prevent SREs, which are among the most debilitating complications of metastatic bone disease. It also supports the hypothesis that early intervention with ZetaMet™ may improve overall survival by reducing tumor burden and preserving skeletal integrity.
Regulatory Outlook and Next Steps
With the Phase 2a trial now formally completed, Zetagen Therapeutics is conducting detailed analyses of the full data set. These results will form the foundation for regulatory discussions and planning for further clinical development.
The company intends to submit the full clinical report to Health Canada (HC) and the U.S. Food and Drug Administration (FDA) to support upcoming strategic consultations. These Zetagen regulatory engagements will help define future trial design, potential expansion into broader patient populations, and additional indications.
Given the early strength of the data, potential future studies may explore:
- Broader application of ZetaMet™ across additional cancer types that metastasize to bone
- Dose-response relationships
- Combination strategies with systemic therapies
- Earlier-stage disease applicability
Presentation Details at SABCS 2025
- Abstract Number: 3549
- Presentation Number: PS1-13-18
- Title: Single Intratumoral Drug Injection Yields Complete Response in Metastatic Breast Cancer Bone Lesions: Results from Phase 2a Trial
- Presentation Format: Poster
- Session Date and Time: Wednesday, December 10, 2025, from 12:30 p.m. to 2:00 p.m. CST
The abstract will also be published in the SABCS 2025 Proceedings and highlighted in Clinical Cancer Research, expanding visibility for scientific and clinical audiences worldwide.
Leadership Commentary
Joe C. Loy, Chief Executive Officer of Zetagen Therapeutics, emphasized that these new data provide further validation of ZetaMet’s™ therapeutic potential.
The promising Phase 2a findings for ZetaMet™ mirror our earlier peer-reviewed results, reinforcing the strength of our clinically validated strategy in treating metastatic breast cancer,” Loy stated. “We observed that both treated and adjacent non-treated lesions within the same vertebral body achieved complete response, with no signs of tumor activity and no skeletal-related events—all using the same drug concentration validated in our preclinical studies—strongly affirming the scientific foundation of our approach.”
Loy added that this expanding body of clinical evidence encourages continued development of ZetaMet™ as a potentially transformative therapy for patients with metastatic bone disease.
The acceptance of Zetagen Therapeutics’ abstract for presentation at the 2025 San Antonio Breast Cancer Symposium represents a significant and promising step for the company’s lead candidate, ZetaMet™. The Phase 2a data showcase a compelling combination of strong tumor response, safety, and potential skeletal restoration—attributes that are rarely Zetagen achieved in current standard treatments for bone-metastatic breast cancer.
As the company prepares next steps in collaboration with global regulators, these findings strengthen optimism that ZetaMet™ could become an important new therapeutic option for patients living with advanced breast cancer and bone metastases. If subsequent trials confirm these early results, ZetaMet™ may offer an entirely new clinical paradigm: local, minimally invasive care capable of halting metastatic disease within the bone while promoting structural recovery and long-term protection against debilitating complications. The oncology community will await further updates from Zetagen Therapeutics as it advances toward broader clinical validation and potential regulatory approval.
About ZetaMet™ (Zeta-BC-003)
ZetaMet™ (Zeta-BC-003) is the first-of-its-kind, synthetic, small-molecule, administered intratumorally to minimize off target toxicity, delivered via a proprietary controlled-release carrier intended to resolve metastatic breast cancer bone lesions, inhibit pain while regenerating bone, with the potential to increase survival rates.
The US Food & Drug Administration (FDA) has recognized Zetagen’s discoveries with multiple Breakthrough Designations including ZetaMet™.
Zetagen with FDA and Health Canada (HC) approval via the Expanded Access (Compassionate Use) program has treated eight (8) patients with ZetaMet™ (Zeta-BC-003) with results published in multiple peer-reviewed journals.
Peer-reviewed 2-year follow up clinical data published in 2023 on ZetaMet™ (Zeta-BC-003) demonstrated resolution of seven (7) lytic lesions (radiated and non-radiated), reduction in pain, significant attrition of opioid pain medication (4-fold), prevention of vertebral fracture, and increased survival rate in a patient living with Stage 4 breast cancer.i To view this publication via open access, go to: https://www.tandfonline.com/doi/full/10.2217/pmt-2023-0069
About Zetagen Therapeutics
Zetagen has three novel drugs in development with the Zeta Platform, ZetaMet™ (Zeta-BC-003), for the treatment of metastatic breast cancer to bone, ZetaMast™ (Zeta-MBC-005) for breast cancer liver metastases (BCLM), and ZetaPrime™ (Zeta-PBC-007) for the treatment of Zetagen primary HR+ breast cancer, all with inspiring results. To learn more, visit www.zetagen.com. The entire Zeta platform is designed for intratumoral administration to reduce off-target toxicity, utilizing proprietary carriers—some incorporating our New Molecular Entity. The USPTO has granted Zetagen Composition-of-Matter patents and claims for all three therapeutics.
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