Zetagen Therapeutics, Inc., a private clinical-stage biopharmaceutical company, announced the successful completion of enrollment in their Phase 2a clinical study evaluating ZetaMet™ (Zeta-BC-003) for the treatment of spinal metastatic lytic breast cancer lesions. The study (ClinicalTrials.gov #NCT05280067) represents a significant step forward in addressing a critical unmet need for patients with metastatic bone disease.
"We are excited to reach another critical milestone in the development of ZetaMet™," said Joe C. Loy, Zetagen's Chief Executive Officer. "We launched this study with stage IV breast cancer patients suffering from spinal metastases, because we recognize their severe pain and how debilitating it is, and that current treatments remain largely palliative. Our objective with ZetaMet™ is to eliminate cancer cells responsible for bone destruction, alleviate pain, stimulate the regeneration of bone lost to lytic lesions, enhance overall quality of life, while improving survival rates."
Addressing a Significant Unmet Medical Need
Metastatic lytic bone lesions affect approximately 690,000 patients annually, with current therapies offering primarily palliative rather than curative options. These lesions, which occur when cancer spreads to the bone and causes destruction of bone tissue, are particularly common in advanced breast cancer and can lead to severe pain, fractures, and significantly reduced quality of life.
The 26-week study is being conducted at the University of British Columbia (UBC) in Vancouver, Canada. It will evaluate the safety and efficacy of ZetaMet™ in treating vertebral bone defects created by lytic metastatic breast cancer. Key endpoints include the reduction of skeletal-related events (SREs), pain levels, changes in vertebral body defect size, and postoperative prescribed opioid use.
Zetagen anticipates reporting top-line results in the early fourth quarter of 2025 and plans to submit an Investigational New Drug (IND) application to the U.S. Food and Drug Administration (FDA), leveraging the Breakthrough Therapy designations already granted to the treatment.
ZetaMet™: A Novel Approach to Treating Bone Metastases
ZetaMet™ (Zeta-BC-003) represents a pioneering approach to treating metastatic bone lesions. It is a synthetic small molecule delivered via a proprietary controlled-release carrier, administered locally to the affected area. What distinguishes ZetaMet™ is its unique mechanism of action through a novel molecular pathway that initiates a circuit resulting in tumor cell death.
The treatment is designed to resolve metastatic breast cancer bone lesions, inhibit pain, and regenerate new bone, with the potential to increase survival rates. This multi-faceted approach addresses both the cancer itself and the bone destruction it causes, potentially offering a more comprehensive solution than existing therapies.
Promising Early Clinical Evidence
Peer-reviewed clinical data published in 2023 has already demonstrated promising results for ZetaMet™. A two-year follow-up study showed resolution of seven lytic lesions (both radiated and non-radiated), reduction in pain, significant reduction in opioid pain medication (4-fold), prevention of vertebral fracture, and increased survival rate in a patient living with Stage 4 breast cancer.
These early results were achieved through FDA and Health Canada's Expanded Access (Compassionate Use) programs, which allowed Zetagen to treat several patients with ZetaMet™ prior to the current Phase 2a trial.
Broader Platform for Breast Cancer Treatment
Founded in 2015, Zetagen Therapeutics has developed a comprehensive "Zeta" platform that encompasses multiple breast oncological drug candidates. In addition to ZetaMet™ (Zeta-BC-003), the company is developing ZetaMAST™ (Zeta-MBC-005) and the newly announced ZetaPrime™ (Zeta-PBC-007), all focused on local administration for metastatic and primary breast cancers.
The company plans to present at the upcoming San Antonio Breast Cancer Symposium (SABCS) this December, where they may share additional insights into their development pipeline and clinical progress.
Clinical Trial Design and Next Steps
The Phase 2a trial represents a critical step in ZetaMet™'s clinical development pathway. By focusing specifically on Stage IV breast cancer patients with spinal metastases, Zetagen is targeting a population with severe unmet needs and limited treatment options.
If the Phase 2a results prove positive, Zetagen's path forward would likely include expanded clinical trials and continued engagement with regulatory authorities, building on the Breakthrough Therapy designations already received from the FDA.
For patients suffering from metastatic bone lesions, particularly those with breast cancer that has spread to the spine, ZetaMet™ could potentially offer a new treatment paradigm that goes beyond pain management to address the underlying disease process and bone destruction, potentially improving both quality of life and survival outcomes.
