FDA Grants Fast Track Designation to TLX101-CDx for Imaging Progressive/Recurrent Glioma

The FDA has granted fast track designation to TLX101-CDx (Pixclara; 18F-floretyrosine [18F-FET]) for the characterization of progressive or recurrent glioma using PET.¹

Although guidelines in the United States and Europe indicate amino acid PET for the imaging of gliomas, no targeted PET imaging agent is currently approved by the FDA. TLX101-CDx is designed to target the membrane transport proteins LAT1 and LAT27, enabling TLX101-CDx to be potentially used as a companion diagnostic agent for TTX101—a LAT1-targeted investigational therapy for glioblastoma.

“There is critical unmet need to improve the diagnosis and management of glioma, particularly in the post-treatment setting, and we are excited to leverage the clinical experience at University of California, San Francisco [UCSF] to help make this investigational agent more widely available,” Thomas A. Hope, MD, a professor of radiology at UCSF, stated in a news release. “[TLX101-CDx] has the potential to help determine if a glioma is truly progressing or undergoing a treatment-induced change, known as pseudo-progression, where MRI5—the standard of care [SOC]—can often be inconclusive.”

TLX101 is currently being investigated in combination with best SOC in patients with newly diagnosed glioblastoma in the phase 1 IPAX-2 trial (NCT05450744) and in combination with concomitant external radiation therapy in patients with recurrent IDH1/2-mutated high-grade glioma in the phase 2 IPAX-Linz-01 trial (EudraCT2021-006426-43).^2,3

In October 2020, the FDA granted an orphan drug designation to TLX101-CDx for the imaging of glioma.⁴ Additionally, Telix Pharmaceuticals announced that the company is in the final stages of preparing a new drug application seeking the FDA approval of TLX101-CDx for the characterization of progressive or recurrent glioma in both adult and pediatric patients.¹

“These milestones represent significant progress as we bring this investigational product closer to market in the United States and commercial launch,” Richard Valeix, group chief commercial officer at Telix Pharmaceuticals, added in the news release. “PharmaLogic has rapidly developed an excellent reputation for manufacturing radiopharmaceuticals to rigorous quality standards and will deliver a key component of Telix’s supply chain strategy for TLX101-CDx in the United States, subject to regulatory approval.”

The open-label, single-arm, parallel-group, multicenter, dose-finding IPAX-2 trial is enrolling patients between 18 to no more than 65 years of age with histologically confirmed intracranial glioblastoma per World Health Organization 2021 criteria following surgical resection. Notably, patients with tumors primarily localized in the infratentorial compartment are being excluded. Prior surgery is permitted; however, no prior systemic therapy or radiation for glioblastoma is allowed. A Karnofsky performance status of at least 70 and adequate organ function are also required.²

Key exclusion criteria include the inability to undergo contrast-enhanced MRI; intention to be treated with tumor-treating fields prior to progression; a history or evidence of delayed-type hypersensitivity–dependent chronic infection; hemostaseologic conditions, precluding catheterization or invasive procedures; phenylketonuria; and phenylketonuria. Additionally, patients cannot have concurrent malignancies, unless they have been disease free without intervention for at least 2 years prior to enrollment.

Enrolled patients are receiving TLX101 intravenously in ascending doses in combination with SOC. The primary end points of the trial are the rate and grade of dose-limiting toxicities, as well as safety.

During the study, TLX101-CDx is being used for imaging to identify patients with LAT1 overexpression who would be suitable candidates for TLX101, as well as to generate baseline and follow-up data regarding tumor response and progression. The first patient was dosed in August 2023.⁵

“This unique collaboration between Dr Hope’s team at UCSF and Telix will enable us to utilize our collective clinical data and expertise to facilitate nationwide access to FET PET in the United States while fostering ongoing research and development with the objective of expanding the clinical utility of this advanced imaging agent for the benefit of patients,” David N. Cade, MD, group chief medical officer at Telix Pharmaceuticals, concluded in the press release.¹

References

1. TLX101-CDx (Pixclara) granted FDA fast track designation. News release. Telix Pharmaceuticals. April 16, 2024. Accessed April 16, 2024. https://telixpharma.com/news-views/tlx101-cdx-pixclara-granted-fda-fast-track-designation/
2. 131I-TLX-101 for treatment of newly diagnosed glioblastoma (IPAX-2). ClinicalTrials.gov. Updated July 19, 2023. Accessed April 16, 2024. https://clinicaltrials.gov/study/NCT05450744
3. An open label, single arm monocentric phase II study to evaluate safety, tolerability, and preliminary efficacy of carrier-added 4-L- [131I]iodophenylalanine (131I-IPA), administered as sequential injections in patients with recurrent IDH1/2 high grade glioma (HGG) concomitantly to 2nd line external radiation therapy. Eu Clinical Trials Register. January 10, 2022. Accessed April 16, 2024. https://www.clinicaltrialsregister.eu/ctr-search/trial/2021-006426-43/AT
4. Telix granted FDA orphan drug designation for glioma imaging agent. News release. Telix Pharmaceuticals. October 6, 2020. Accessed April 16, 2024. https://telixpharma.com/news-views/telix-granted-fda-orphan-drug-designation-for-glioma-imaging-agent/
5. First patient dosed in IPAX-2 study of TLX101 brain cancer therapy candidate in patients with newly diagnosed glioblastoma. News release. Telix Pharmaceuticals. August 8, 2023. Accessed April 16, 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/