Telix Pharmaceuticals has announced promising preliminary results from its phase 2 IPAX-Linz study evaluating TLX101 (131I-iodofalan) in patients with recurrent high-grade glioma, a particularly aggressive form of brain cancer.
The investigational targeted radiation therapy demonstrated a median overall survival of 12.4 months from treatment initiation and 32.2 months from initial diagnosis. These results are consistent with data previously observed in the IPAX-1 study and compare favorably to the 9.9-month median survival typically seen with external beam radiation therapy alone in recurrent glioblastoma.
"These preliminary results in relapsed patients showed that TLX101 treatment was very well tolerated, with no serious adverse events, at a higher dose than in previous studies," said Professor Josef Pichler of Kepler University Hospital in Austria, principal investigator of the IPAX-Linz, IPAX-1, and IPAX-2 studies.
Study Design and Patient Population
The phase 2 IPAX-Linz trial evaluated TLX101 in combination with external beam radiation therapy in eight patients with recurrent high-grade glioma. Participants received adaptive intravenous dosing of TLX101—up to 4 gigabecquerels (GBq) before and up to 2 GBq after a second course of external beam radiation therapy.
Notably, five of the eight participants had tumors with unmethylated MGMT genes, a characteristic typically associated with poorer treatment outcomes. Despite these challenging prognostic factors, the treatment showed encouraging efficacy.
"Early efficacy from IPAX-1 was corroborated, despite the poor prognostic parameters with MGMT unmethylated tumors and multiple relapses before commencing experimental therapy in this IPAX-Linz study," Professor Pichler noted. "TLX101 continues to show significant potential to improve outcomes for patients living with high-grade glioma."
Eligibility criteria for the trial included:
- Diagnosis of glioblastoma with evidence of first or second recurrence after standard radiochemotherapy
- At least six months since completion of first-line external beam radiation therapy
- Imaging with TLX101-CDx (18F-floretyrosine; 18F-FET; Pixclara) indicating increased amino acid uptake
Mechanism of Action
TLX101 represents an innovative approach to treating brain tumors. It is a targeted radiation treatment administered intravenously and designed to attach specifically to the LAT1 protein, which is highly expressed in glioblastoma cells. As a small molecule, TLX101 can penetrate the blood-brain barrier, allowing it to reach the tumor site effectively.
The treatment works in conjunction with TLX101-CDx, a companion diagnostic imaging agent that helps identify tumors with unusually high amino acid activity, potentially allowing for better patient selection.
Regulatory Status and Future Directions
TLX101 has received orphan drug designation in both the United States and Europe, recognizing its potential in treating rare diseases like high-grade glioma. Additionally, TLX101-CDx received FDA fast track designation in progressive or recurrent glioma in April 2024 and FDA priority review in October 2024.
Dr. David Cade, Chief Medical Officer at Telix, expressed optimism about the findings: "These are encouraging results, offering new options for patients with historically poor outcomes. We are grateful to Dr. Pichler and his team for building on the IPAX-1 study in a more advanced and complex study cohort that is also representative of a real-world patient population."
Professor Pichler will present more comprehensive preliminary results at the Nuclear Medicine and Neuro-oncology Symposium in Vienna, Austria, scheduled for May 9-10, 2025.
Broader Clinical Program
Telix continues to investigate TLX101 in both front-line and recurrent treatment settings. The phase 1/2 IPAX-2 clinical trial, which is evaluating standard of care with TLX101-CDx as a companion diagnostic, continues to recruit patients with front-line glioblastoma.
These latest results build upon previous findings from the phase 1 IPAX-1 trial, which showed a median overall survival of 13 months from treatment initiation and 23 months from initial diagnosis. In that study, the treatment demonstrated a manageable safety profile with most treatment-emergent adverse events being mild or moderate in nature.
The consistent efficacy signals across multiple studies and the favorable safety profile at higher doses suggest that TLX101 may represent a meaningful advancement in the treatment landscape for patients with high-grade glioma, a population with significant unmet medical needs.
"These results also potentially support higher therapeutic doses in subsequent prospective controlled studies," Professor Pichler concluded, pointing to future directions for the clinical development program.
