First Patient Dosed in Pioneering ZOLAR Trial of TLX300-CDx for Advanced Soft Tissue Sarcoma
Key Insights
Telix Pharmaceuticals has dosed the first patient in its Phase 1 ZOLAR trial evaluating TLX300-CDx (89Zr-olaratumab) in patients with advanced soft tissue sarcoma (search) at Melbourne Theranostic Innovation Centre.
The first-in-human trial aims to assess safety, pharmacokinetics, and optimal dosing of the radiopharmaceutical targeting platelet-derived growth factor receptor alpha (search) (PDGFRα (search)), which is often overexpressed in soft tissue sarcomas.
This theranostic approach could lead to a novel targeted radionuclide therapy for soft tissue sarcoma (search), a rare cancer with limited treatment options and poor prognosis for patients with metastatic disease.
Telix Pharmaceuticals has announced the dosing of the first patient in its Phase 1 ZOLAR trial, evaluating TLX300-CDx (89Zr-olaratumab) in patients with advanced, metastatic soft tissue sarcoma (search) (STS). The milestone was achieved at the Melbourne Theranostic Innovation Centre (MTIC) in Australia, marking an important step in developing new treatment options for this rare and challenging cancer.
The ZOLAR trial represents the first-in-human study of olaratumab as a radiopharmaceutical targeting platform. Olaratumab is a monoclonal antibody that targets platelet-derived growth factor receptor alpha (search) (PDGFRα (search)), a cell surface protein frequently overexpressed in soft tissue sarcomas.
Theranostic Approach to Soft Tissue Sarcoma
The trial employs positron emission tomography (PET) to evaluate the safety, pharmacokinetics, biodistribution, and dosimetry of TLX300-CDx. This diagnostic imaging approach will help establish the optimal dose for patients with advanced STS before proceeding to therapeutic studies.
Professor Rodney Hicks AM, Founder, Chair, and Chief Medical Officer at MTIC, and Principal ZOLAR Investigator, highlighted the challenges in treating sarcomas: "Sarcomas are individually very rare and they can arise from a variety of different tissues. Unfortunately, they tend to respond rather poorly to chemotherapy. While localized STS generally responds to radiotherapy, it is challenging to treat once it has spread."
He added, "Targeted radionuclide therapy, which targets cancer cells throughout the body, is therefore an attractive option to treat disseminated disease. At MTIC, we're fortunate to be the first site validating this investigational agent as a precision diagnostic and to inform the design of future therapeutic studies."
Addressing an Unmet Medical Need
Soft tissue sarcoma (search) encompasses more than 50 malignant histological subtypes. In the United States, approximately 13,520 new diagnoses and 5,420 deaths from STS are expected in 2025, representing 0.66% of overall cancer incidence and 0.88% of overall cancer mortality.
Current treatment options for advanced STS include surgery, radiation therapy, and chemotherapy, typically with single agents like doxorubicin or anthracycline-based combination regimens. However, the prognosis remains poor, with treated patients with metastatic disease having a median overall survival of only 12–18 months.
Dr. David N. Cade, Telix Group Chief Medical Officer, expressed optimism about the trial's potential: "We are pleased that a first patient has been imaged in the first-in-human ZOLAR trial, which is designed to inform both the potential efficacy (dosimetry) and safety profile of this research candidate as a therapeutic, based on a theranostic approach."
Repurposing Olaratumab for Radiopharmaceutical Development
Olaratumab, previously marketed under the brand name Lartruvo®, was originally developed by Eli Lilly and Company as a monoclonal antibody targeting PDGFRα (search). Although it received "Accelerated Approval" in the U.S. and "Conditional Approval" in the EU based on Phase 2 trial data, it was voluntarily withdrawn from the market following the failure of the Phase 3 ANNOUNCE clinical trial.
In April 2022, Telix secured exclusive worldwide rights to develop and commercialize radiolabelled forms of olaratumab for the diagnosis and treatment of human cancers. The company is leveraging olaratumab's established clinical safety profile and favorable toxicology dataset for radiopharmaceutical development.
Patient Selection and Future Therapeutic Applications
The ZOLAR trial will not only evaluate the safety and optimal dosing of TLX300-CDx but also inform the selection of the most appropriate therapeutic radionuclide for future development. Patient dosimetry and target expression characteristics, combined with ongoing non-clinical radiation biology studies, will guide Telix's development of a novel targeted radionuclide therapy specific for PDGFRα (search).
If successful, this approach could provide a much-needed treatment option for patients with advanced soft tissue sarcoma (search), who currently face limited therapeutic alternatives and poor outcomes.
TLX300-CDx has not yet received marketing authorization in any jurisdiction, and the ZOLAR trial represents an early but crucial step in its clinical development pathway.