Zetagen Therapeutics Reports Promising Phase 2a Results for Investigational ZetaMet™ in Metastatic Breast Cancer Patients With Lytic Bone Lesions
Zetagen Therapeutics, a clinical-stage biopharmaceutical company focused on developing innovative therapies for primary and metastatic breast cancer, has released updated preliminary results from its Phase 2a clinical trial evaluating ZetaMet™ (Zeta BC 003), an investigational treatment for patients with metastatic breast cancer (MBC) who have developed lytic bone lesions. The findings, which were presented at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting, highlight encouraging clinical outcomes related to tumor control, bone healing, pain reduction, and quality-of-life improvements.
Alongside the results, the company issued a clarification regarding a statement contained in an earlier version of its announcement distributed on June 9, 2026. Zetagen noted that the previous release incorrectly stated that the study reported no treatment-emergent adverse events. The company clarified that the correct finding was that no treatment-related adverse events or serious adverse events were observed during the study. All other reported study data remain unchanged.
Zetagen emphasized that the correction was made to ensure the accuracy and transparency of its communications regarding the clinical development program.
Investigating a New Approach to Bone Metastases
Bone metastases are a common and serious complication of advanced breast cancer. Many patients with metastatic breast cancer experience the spread of cancer cells to bone tissue, leading to lytic lesions that weaken bone structure and increase the risk of fractures, severe pain, spinal instability, and other skeletal-related events (SREs).
Despite advances in oncology, managing bone metastases remains a significant clinical challenge. Existing therapies such as bisphosphonates and other bone-targeted agents can help reduce complications, but many patients continue to experience disease progression and skeletal deterioration.
ZetaMet has been developed as a novel intratumoral therapy designed to directly target cancerous bone lesions while promoting structural restoration within affected bone tissue. The investigational treatment has received Breakthrough Designation from the U.S. Food and Drug Administration, reflecting its potential to address a significant unmet medical need. However, the Zetagen therapy remains experimental and has not yet received regulatory approval in the United States or any other jurisdiction.
Encouraging Early Clinical Findings
According to Zetagen President and Chief Executive Officer Joe C. Loy, the preliminary Phase 2a findings represent an important milestone for both the company and the broader field of bone metastasis treatment.
Loy stated that the results provide meaningful clinical observations regarding the potential role of ZetaMet in treating metastatic breast cancer patients with bone involvement. He also highlighted the company’s success in addressing one of the longstanding technical challenges associated with intratumoral therapies: delivering therapeutic compounds directly into tumors while ensuring adequate solubility and localized retention.
Through the development of proprietary carrier technologies, Zetagen believes it has created a platform capable of improving the precision and effectiveness of localized treatment delivery.
The preliminary results were presented during the ASCO Annual Meeting by Dr. Bryan Margulies, the company’s Chief Scientific Officer, alongside Loy.
Phase 2a Trial Design
The open-label Phase 2a study, known as ZGMBC (NCT05280067), was conducted at the University of British Columbia and enrolled ten patients diagnosed with metastatic breast cancer involving lytic bone lesions.
Participants had an average age of 52 years and represented a range of breast cancer subtypes, including:
- Hormone receptor-positive (HR+) disease: 6 patients
- HR-positive/HER2-positive disease: 2 patients
- HER2-positive/hormone receptor-negative disease: 1 patient
- Triple-negative breast cancer (TNBC): 1 patient
Notably, five participants had experienced breakthrough lytic lesions despite receiving prior bisphosphonate Zetagen therapy, indicating disease progression despite standard bone-targeted treatment.
Across the study population, investigators treated 11 target lesions using a single intratumoral injection of Zeta BC 003 administered under sedation. In addition to the injected lesions, researchers also monitored four nearby untreated lesions located within the same vertebral structures to evaluate potential secondary effects of treatment.
One participant died during the study as a result of pleural edema. Investigators determined that the event was unrelated to the study treatment.
No Skeletal-Related Events or Fractures Observed
One of the most notable findings from the trial was the absence of skeletal-related events and fractures among study participants.
Skeletal-related events are among the most serious complications associated with metastatic bone disease. These events can include pathological fractures, spinal cord compression, and the need for radiation or surgical intervention. Such complications often lead to reduced mobility, diminished quality of life, increased healthcare utilization, and poorer survival outcomes.
Historical studies have reported skeletal-related event rates of approximately 53% among patients with metastatic breast cancer involving bone. Previous research has also demonstrated that fractures and related complications can significantly reduce overall survival.
Against this backdrop, the absence of reported skeletal-related events during the study period represents an encouraging observation that warrants further investigation in larger clinical trials.
Evidence of Tumor Control and Bone Healing
Researchers also reported cessation of tumor activity within treated vertebral bodies following administration of ZetaMet.
Beyond controlling tumor activity, the study demonstrated significant reductions in bone defect volume over time, suggesting potential restoration of bone structure.
By Day 84 following treatment, mean bone defect volume had decreased by 65.4%, a statistically significant improvement. By Day 180, the reduction had increased to 84.1%, indicating continued healing and remodeling of affected bone tissue.
These findings suggest that the investigational Zetagen therapy may contribute not only to controlling cancer-related damage but also to supporting structural recovery within weakened bones.
Therapeutic Effects Beyond the Injection Site
An additional observation that attracted attention was evidence of therapeutic activity in adjacent lesions that had not been directly injected with the treatment.
Researchers reported signs of therapeutic spread within treated vertebral bodies, with neighboring untreated lesions demonstrating beneficial effects. This observation may indicate that the Zetagen therapy exerts influence beyond the immediate injection site, potentially expanding its impact within affected skeletal regions.
Similar findings had previously been documented in expanded access case reports involving patients treated with ZetaMet, providing further support for this phenomenon.
While the underlying mechanisms require additional investigation, the observation raises the possibility that localized treatment could generate broader therapeutic effects within metastatic bone lesions.
Favorable Safety and Tolerability Profile
Safety remains a primary consideration in the development of any cancer Zetagen therapy, particularly for patients with advanced metastatic disease.
The Phase 2a study reported no treatment-related adverse events and no treatment-related serious adverse events among participants. This finding suggests that the Zetagen therapy was generally well tolerated within the study population.
Although the trial was relatively small and further evaluation is necessary, the absence of treatment-related safety concerns provides support for continued clinical development.
Company officials emphasized that the findings should be interpreted cautiously given the limited sample size but noted that the safety observations align with previous clinical experiences involving the investigational therapy.
Improvements in Pain, Opioid Use, and Quality of Life
In addition to structural and tumor-related outcomes, the study demonstrated meaningful improvements in patient-reported measures.
Pain scores, assessed using the Numerical Rating Scale (NRS), declined by an average of 4.16 points, representing a statistically significant reduction in pain severity.
Patients who were receiving opioid medications also experienced notable decreases in opioid consumption. Depending on the individual patient, opioid use declined between 33% and 67%, suggesting that symptom improvement translated into reduced reliance on pain medication.
Spinal stability, measured using the Spinal Instability Neoplastic Score (SINS), improved by 18.5%, indicating enhanced structural integrity of affected vertebrae.
Quality-of-life assessments also showed positive changes:
- Physical Component Summary (PCS) scores increased by 24.2%.
- Mental Component Summary (MCS) scores increased by 12.1%.
These improvements suggest that the observed clinical benefits may have translated into meaningful gains in daily functioning and overall well-being.
Consistency With Previous Expanded Access Experience
The Phase 2a findings are consistent with previously published expanded access reports involving seven metastatic bone lesions followed over a two-year period.
Those earlier reports similarly documented an absence of skeletal-related events, cessation of tumor activity, evidence of new bone formation, and therapeutic effects extending beyond the directly treated lesion.
The consistency between the expanded access experience and the current clinical study strengthens confidence in the reproducibility of the observed effects and supports further investigation in larger patient populations.
Collaboration Supporting Clinical Development
Zetagen acknowledged the contributions of several clinical and operational partners that supported the study.
The company expressed appreciation to the University of British Columbia for conducting the clinical research, while Nor Consult, LLC provided comprehensive clinical operations support throughout the trial. Medical Medics Incorporated supplied centralized imaging services, helping ensure standardized imaging assessments and high-quality data collection.
These collaborations played a key role in executing the study and generating the clinical observations reported at ASCO.
While additional studies will be needed to confirm efficacy and establish long-term outcomes, the preliminary Phase 2a results provide encouraging evidence supporting the continued development of ZetaMet for patients with metastatic breast cancer involving lytic bone lesions.
The combination of observed tumor control, bone healing, pain reduction, improved spinal stability, enhanced quality of life, and a favorable safety profile suggests that the investigational therapy could potentially address multiple challenges associated with metastatic bone disease. As Zetagen advances its clinical program, future studies will determine whether these early findings can be replicated in larger patient populations and ultimately support regulatory approval of this novel therapeutic approach.
About ZetaMet™ (Zeta BC 003)
ZetaMet™ is designed for single intratumoral administration into lytic bone lesions associated with metastatic breast cancer. Preclinical and clinical studies suggest the potential for ZetaMet™ to cease lytic activity, reducing pain, initiating bone healing, and prevent SREs; however, ZetaMet™ has not been approved by the FDA or any regulatory authority.
About Zetagen Therapeutics
Zetagen Therapeutics is a clinical‑stage biopharmaceutical company focused on developing novel therapies for primary and metastatic breast cancer. The Zetagen company’s “Zeta”‑platform is designed to address historical challenges in intratumoral delivery through our proprietary carriers and NMEs to support compound solubility and localized bio‑adhesion, with the goal of minimizing off‑target toxicity.
