NDA Submitted to FDA for TLX101-CDx in Progressive/Recurrent Glioma

A new drug application (NDA) has been submitted to the FDA seeking the approval of the investigational PET brain cancer imaging agent TLX101-CDx (Pixclara; ¹⁸F-floretyrosine; ¹⁸F-FET) for the characterization of progressive or recurrent glioma for treatment-related changes in both adult and pediatric patients.¹

“Gliomas are the most common primary brain tumors of the central nervous system. Conventional imaging with MRI often yields inconclusive results in characterizing recurrent disease and therefore delays time-sensitive decision making. Limitations of conventional imaging techniques include the lack of biological specificity, dependency on blood-brain barrier disruption, and an inherent inability to differentiate between tumor progression or treatment-related causes,” Kevin Richardson, chief executive officer of Telix Precision Medicine, stated in a news release. “Telix’s filing of this NDA for [TLX101-CDx] is an important milestone, reflecting our commitment to improved and accessible neuro-oncology imaging in the United States, and taking us one step closer to commercial availability in 2025, subject to FDA approval.”

Previously, TLX101-CDx was granted orphan drug and fast track designations by the FDA for imaging in progressive or recurrent glioma. TLX101-CDx is already included in international clinical practice guidelines for glioma imaging, however, no targeted amino acid PET agent is currently FDA approved for adult and pediatric brain cancer imaging.

TLX101-CDx, which targets the membrane transport proteins LAT1 and LAT2, is also being developed as the companion theranostic imaging agent for the investigational neuro-oncology drug candidate TLX101 (4-L-[¹³¹I] iodo-phenylalanine; ¹³¹I-IPA), which targets the same amino acid transporter mechanism as TLX101-CDx via targeted therapeutic radiation. TLX101 is under investigation in the phase 1 IPAX-2 (NCT05450744) and phase 2 IPAX-Linz (EudraCT2021-006426-43) trials.

The ongoing open-label, single-arm, parallel-group, multicenter, dose-finding IPAX-2 trial is investigating the safety of ascending dose levels of intravenous TLX101 plus best standard of care (external-beam radiation therapy [EBRT] and temozolomide [Temodar]) in patients with newly diagnosed glioblastoma.^2,3

Patients between 18 and 65 years of age are eligible for enrollment if they have histologically confirmed intracranial glioblastoma following surgical resection, a Karnofsky performance status of at least 70, plans to begin chemoradiation 3 to 6 weeks after surgical resection, adequate organ function at screening, and at least 6 slides without staining or a tissue block available from a prior biopsy or surgery.² Patients are not permitted to have tumors primarily localized in the infratentorial compartment or have received prior systemic or radiation therapy for glioblastoma. The primary end points of this study are the incidence and severity of dose-limiting toxicities, as well as safety, tolerability, and the determination of the recommended phase 2 dose.

On August 8, 2023, it was announced that the first patient was dosed in IPAX-2,³ which has a planned enrollment of 12 patients. Investigators aim to observe whether the safety and drug interaction profile of the combination are suitable in the frontline setting before progressing to a phase 2 proof-of-concept trial.

IPAX-Linz is evaluating TLX101 in combination with EBRT as second-line treatment in patients with recurrent high-grade gliomas, including glioblastoma multiforme (GBM).⁴ The first patient was dosed in IPAX-Linz on November 22, 2022. This trial has a target enrollment of 10 patients, and the aim of this study is to collect additional data on the clinical utility of the combination.

IPAX-2 and IPAX-Linz build on data from the phase 1/2 IPAX-1 trial (NCT03849105), final results from which were reported in September 2022.^3,4 In IPAX-1, TLX101 plus EBRT had a favorable safety profile and demonstrated preliminary efficacy among 9 patients with recurrent GBM who received the full study treatment dosing of approximately 2 GBq of TLX101.⁵ The median overall survival was 13 months from treatment initiation in the recurrent setting and 23 months from initial diagnosis. The most frequent treatment-emergent adverse effects were decreased lymphocyte count, headache and hiccups, and fatigue, which occurred in 3 patients, as well as decreased platelet count, cerebral edema, diarrhea, and insomnia, which occurred in 2 patients.

References

1. Telix submits NDA for TLX101-CDx (Pixclara) brain cancer imaging agent. News release. Telix. August 28, 2024. Accessed August 28, 2024. https://telixpharma.com/news-views/telix-submits-nda-for-tlx101-cdx-pixclara-brain-cancer-imaging-agent/
2. 131I-TLX-101 for treatment of newly diagnosed glioblastoma (IPAX-2) (IPAX-2). ClinicalTrials.gov. Updated July 19, 2023. Accessed August 28, 2024. https://clinicaltrials.gov/study/NCT05450744
3. First patient dosed in IPAX-2 study of TLX101 brain cancer therapy candidate in patients with newly diagnosed glioblastoma. News release. Telix. August 8, 2023. Accessed August 28, 2024. https://telixpharma.com/news-views/first-patient-dosed-in-ipax-2-study-of-tlx101-brain-cancer-therapy-candidate-in-patients-with-newly-diagnosed-glioblastoma/
4. First patient dosed in phase II ‘IPAX-Linz’ study of TLX101 for glioblastoma therapy. News release. Telix. November 22, 2022. Accessed August 28, 2024. https://telixpharma.com/news-views/first-patient-dosed-in-phase-ii-ipax-linz-study-of-tlx101-for-glioblastoma-therapy/
5. Final IPAX-1 study data confirms safety and tolerability profile for TLX101, preliminary efficacy data. News release. Telix. September 21, 2022. Accessed August 28, 2024. https://telixpharma.com/news-views/final-ipax-1-study-data-confirms-safety-and-tolerability-profile-for-tlx101-preliminary-efficacy-data/