TLX101 Has Preliminary Safety and Clinical Activity in Recurrent High-Grade Glioma

TLX101 in Recurrent High-Grade Glioma

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TLX101 (¹³¹I-iodofalan), an investigational targeted radiotherapy, was associated with a favorable safety profile and demonstrated early signs of clinical activity in patients with recurrent high-grade glioma (HGG), according to preliminary results from the phase 2 IPAX-Linz study.1

Among the 8 enrolled patients with HGG in first or second recurrence, treatment with TLX101 was well tolerated, with no serious adverse effects (AEs) reported. The median overall survival (OS) from initiation of TLX101 was 12.4 months, and the median OS from initial diagnosis was 32.2 months. Patients needed to have a minimum interval of 6 months from the completion of first-line external beam radiation therapy (EBRT) and evidence of increased amino acid uptake on molecular imaging with TLX101-CDx, Telix’s investigational PET agent. Enrolled patients received adaptive dosing of intravenous TLX101, with administered activity of up to 4 GBq prior to second-line EBRT and up to 2 GBq following EBRT. TLX101 was delivered in sequential injections. Among the 8 patients included in the study, 5 had MGMT-unmethylated tumors, a glioblastoma subgroup associated with poor prognosis.

These findings support the positive efficacy signal observed with the agent in the phase 1/2 IPAX-1 study, (NCT03849105), which reported a median OS of 13.0 months from treatment initiation and 23.0 months from diagnosis in a similar patient population.

“These preliminary results in relapsed patients showed that TLX101 treatment was very well tolerated, with no serious AEs, at a higher dose than in previous studies,” Josef Pichler, MD, of Kepler University Hospital, Austria, principal investigator of the IPAX-Linz, IPAX-1, and phase 1 IPAX-2 (NCT05450744) studies, noted in a news release. “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. TLX101 continues to show significant potential to improve outcomes for patients living with HGG. These results also potentially support higher therapeutic doses in subsequent prospective controlled studies.”

Preliminary results from IPAX-Linz will be presented by Pichler at the Nuclear Medicine and Neurooncology Symposium taking place in Vienna, Austria from May 9 to 10, 2025.

“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,” David Cade, MBBS, Chief Medical Officer at Telix, added in the news release.1

Highlighting the Investigation of TLX101 in Newly Diagnosed Glioblastoma

Building on prior findings with TLX101 in patients with recurrent HGG, the ongoing IPAX-2 study is investigating the agent in patients with newly diagnosed glioblastoma.2 The trial is currently enrolling patients 18 to 65 years of age who have histologically confirmed intracranial glioblastoma defined by World Health Organization 2021 criteria following surgical resection. Patients with tumors primarily localized in the infratentorial compartment will be excluded. Patients must not have received prior systemic therapy or radiation for glioblastoma but are required to have undergone prior surgery. All patients will be expected to initiate chemoradiation therapy 3 to 6 weeks post-resection.

Additional eligibility criteria include a Karnofsky performance status of at least 70, as well as adequate bone marrow, liver, and renal function. Patients need to have available tumor tissue from a prior biopsy or surgery, be capable of understanding and complying with all study procedures—including radiation protection protocols, and agree to appropriate contraceptive measures. Female patients will be required to test negative for pregnancy at screening and on the day of dosing and cannot be lactating.

Key exclusion criteria include prior treatment for glioma other than surgery, inability to undergo contrast-enhanced MRI, and planned use of tumor-treating fields prior to progression. Patients with medical contraindications to treatment, such as active or chronic infections (e.g., tuberculosis), hypersensitivity to study drugs or excipients, bleeding disorders, or significant psychiatric conditions, will be excluded. Additionally, patients will be excluded if they have undergone major surgery within 3 weeks, excluding glioma resection; have ongoing use of high-dose corticosteroids; or have uncontrolled infections or concurrent malignancies not in remission for at least 2 years.

Patients will also be excluded if they require concurrent anticancer therapies, have received growth factors or immunomodulatory agents within 7 days, or have unresolved grade 1 or higher AEs following surgery. Pregnant or breastfeeding patients and those planning pregnancy during the study period will not be eligible for enrollment. Other exclusion criteria include use of another investigational drug within 90 days, uncontrolled thyroid disorders, and serious nonhealing wounds or fractures.

Notably, TLX101 has received orphan drug designation in the United States and Europe for the treatment of patients with glioma.1 TLX101 and TLX101-CDx have not received marketing authorization in any jurisdiction.

References

1. IPAX-Linz study reports promising efficacy for TLX101 glioma therapy candidate. News Release. Telix Pharmaceuticals Limited. April 15, 2025. Accessed April 16, 2025. https://ir.telixpharma.com/news-releases/news-release-details/ipax-linz-study-reports-promising-efficacy-tlx101-glioma-therapy
2. 131I-TLX-101 for treatment of newly diagnosed glioblastoma (IPAX-2). ClinicalTrials.gov Updated July 19, 2023. Accessed April 16, 2025. https://clinicaltrials.gov/study/NCT05450744