Preliminary TLX101 Results Show Promise in High-Grade Recurrent Glioma

Results from the phase 2 IPAX-Linz trial showed TLX101 with EBRT improved overall survival in recurrent high-grade glioma.

TLX101 (¹³¹I-iodofalan) demonstrated promising efficacy and a tolerable safety profile in the treatment of a small cohort of patients with recurrent high-grade glioma in the phase 2 IPAX-Linz trial (2021-006426-43), according to results shared in a press release from the developer, Telix.¹

The treatment elicited a median overall survival (OS) of 12.4 months from the initiation of TLX101 dosing and a median OS of 32.2 months from initial diagnosis. Additionally, the study reported that there were no serious adverse events (AEs).

These results were consistent with previously reported data from the phase 1 IPAX-1 trial (NCT03849105) that showed a median OS of 13 months (95% CI, 7.1-27.0) from initiation of treatment and 23 months from initial diagnosis.² The study authors noted that, previously, patients with recurrent glioblastoma who were treated with external beam radiation therapy (EBRT) alone experienced a median OS of 9.9 months from treatment initiation.³

IPAX-Linz is a single-arm, investigator-initiated trial evaluating the safety, tolerability, and preliminary efficacy of TLX101 therapy when given in combination with EBRT.

TLX101 is also being assessed in patients in the IPAX-1 trial and the phase 2 IPAX-2 trial (NCT05450744). Based on data from all 3 trials, TLX101-CDx (¹⁸F-floretyrosine; ¹⁸F-FET; Pixclara) received FDA fast track designation in progressive or recurrent glioma in April 2024, and FDA priority review in progressive or recurrent glioma in October 2024.^4,5

More comprehensive preliminary results are planned to be shared at the Nuclear Medicine and Neurooncology Symposium in Vienna, Austria, from May 9 to 10, 2025.

“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. 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,” said Professor Josef Pichler, MD, of Kepler University Hospital, Austria, and principal investigator of the IPAX-Linz, IPAX-1, and IPAX-2 trials.¹ “TLX101 continues to show significant potential to improve outcomes for patients living with high-grade glioma. These results also potentially support higher therapeutic doses in subsequent prospective controlled studies.”

IPAX-Linz included a total of 8 patients who received adaptive dosing of intravenous TLX101 up to 4GBq before, and 2GBq after, second-line EBRT that was administered in sequential injections. Of the patients enrolled, 5 had MGMT unmethylated tumors.

Eligible patients had diagnosis of glioblastoma with current evidence of first or second recurrence after standard radiochemotherapy, 6 months or more time since the end of first-line EBRT, and imaging conducted with TLX101-CDx pathologically indicating increased amino acid uptake. Patients were also permitted to have surgery for relapsed tumors.

In November 2022, it was reported that the first patient was dosed with TLX101 in the IPAX-Linz study.⁶

In the IPAX-1 trial, 53 AEs were observed; 87% of treatment-emergent AEs (TEAEs) were considered mild or moderate in nature.² A total of 4 serious AEs were reported in 3 patients and were possibly related to treatment; 2 events were brain edema, 1 was increased intracranial pressure, and 1 was decreased platelet count. The most common TEAEs were decreased lymphocyte counts, headache, hiccups, and fatigue.

David Cade, chief medical officer at Telix, said, “These are encouraging results, offering new options for patients with historically poor outcomes. We are grateful to 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.”¹

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://tinyurl.com/23fdspjf
2. Pichler J, Traub-Weidinger T, Spiegl K, et al. Results from a phase I study of 4-l-[131I]iodo-phenylalanine ([¹³¹I]IPA) with external radiation therapy in patients with recurrent glioblastoma (IPAX-1). Neurooncol Adv. 2024;6(1):vdae130. Published 2024 Jul 29. doi:10.1093/noajnl/vdae130
3. Kulinich DP, Sheppard JP, Nguyen T, et al. Radiotherapy versus combination radiotherapy-bevacizumab for the treatment of recurrent high-grade glioma: a systematic review. Acta Neurochir (Wien). 2021;163(7):1921-1934. doi:10.1007/s00701-021-04794-3
4. TLX101-CDx (Pixclara™) granted FDA fast track designation. News release. Telix Pharmaceuticals Limited. April 15, 2024. Accessed April 16, 2025. https://tinyurl.com/2fu33ryy
5. FDA accepts new drug application and grants priority review for TLX101CDx (Pixclara®) brain cancer imaging agent. News release. Telix Pharmaceuticals Limited. October 24, 2024. Accessed April 16, 2025. https://tinyurl.com/ytm76yaa
6. First patient dosed in phase II 'IPAX-Linz' study of TLX101 for glioblastoma therapy. News release. Telix Pharmaceuticals Limited. November 21, 2022. Accessed April 16, 2025. https://tinyurl.com/55wjdsd5