Study of TLX101-Tx Plus Standard of Care (SoC) Versus SoC Alone for the Treatment of Patients With Recurrent Glioblastoma

NCT07100730 | Recruiting Phase 3 DMC

• 2 other identifiers: 131I-TLX-101-0032025-521785-10
• Study Type: interventional
• Target: 50
• Locations: 2 countries
• Sites: 2

Brief Summary

This global clinical trial which evaluates the efficacy and safety of TLX101-Tx, an investigational radiopharmaceutical therapy, in combination with lomustine versus lomustine alone in adult patients with first recurrence of glioblastoma. TLX101-Tx delivers targeted radiation to glioblastoma cells. The trial is conducted in two parts: Part 1 assesses safety and radiation dosing; Part 2 is a randomized comparison of the combination therapy against standard care.

Conditions

Glioblastoma (GBM); Glioblastoma Multiform; Glioblastoma Multiforme, Adult; Glioblastoma Multiforme (GBM) WHO Grade IV; Neoplastic Disease; Glioblastoma

Keywords

Lomustine; Radiation Therapy; Radiopharmaceuticals; Positron-Emission Tomography; Brain Neoplasms; Glioblastoma Multiforme; Glioblastoma; GBM; Neoplasm Recurrence, Local; Central Nervous System Neoplasms; Brain cancer; Recurrent brain tumor; Brain tumor recurrence; LAT-1 targeted therapy

Outcome Measures

Primary Outcomes (2)

• Safety and Tolerability

  Assessing TEAEs type according to MedDRA (Medical Dictionary for Regulatory Activities), frequency, severity according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) V5.0, seriousness, and relationship of study treatment will be assessed. Laboratory abnormalities will be assessed according to the NCI CTCAE V5.0.

  Through study completion, an average of 2 years

• Dose Optimization

  Part 1 of the study is being done to identify the best dose to use for Part 2 of the study

  Through study completion, an average of 2 years

Secondary Outcomes (3)

• TLX101-Tx Concentration in the blood

  From enrollment to the end of treatment at around 12 weeks.

• Radiation Dosimetry

  Through study completion, an average of 2 years

• TLX101-Tx Concentration in the Urine

  From enrollment to the end of treatment at around 12 weeks.

Study Arms (2)

TLX101-Tx + Standard of Care

EXPERIMENTAL

TLX101-Tx + Lomustine

Combination Product: TLX-101-Tx + Lomustine

TLX101-Tx Only

EXPERIMENTAL

TLX101-Tx Therapy only

Radiation: TLX101-Tx

Interventions

TLX-101-Tx + Lomustine COMBINATION_PRODUCT

Combination therapy with TLX-101-Tx + Lomustine

Also known as: 131I-IPA, 131I-TLX101

TLX101-Tx + Standard of Care

TLX101-Tx RADIATION

TLX101-Tx

Also known as: 131I-IPA, 131I-TLX101

TLX101-Tx Only

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Previously confirmed neuropathological diagnosis of glioblastoma, IDH-wildtype according to the WHO 2021 classification.
• Radiographic evidence of first recurrence or progressive glioblastoma according to RANO 2.0 criteria after first-line treatment with biopsy or maximal safe resection and standard radiotherapy or chemoradiotherapy having occurred at least 3 months after the end of prior radiotherapy. Prior first-line therapy may include a combination of:
• Any systemic antineoplastic treatment other than nitroureas
• Tumor-treating fields
• Conventionally fractionated or abbreviated (minimum 15 fractions) radiotherapy
• Increased \[18F\]\]FET PET tracer uptake inside or in the vicinity of tumor. Specifically, amino acid-based molecular imaging using \[18F\]FET PET will be evaluated following co-registration with MRI. The allocated physician/reader will assess whether the observed pathologically increased amino acid uptake is located within the tumor or in the vicinity. This determination will serve as a guidance to confirm whether the uptake is tumor-associated. The uptake must be clearly discernible from background activity and measurable per PET RANO 1.0 criteria, as determined by central review.
• Tumor debulking for recurrent, progressive disease is allowed. The patient must have post-surgical (4-6 weeks) radiographic evidence for residual tumor according to RANO 2.0 with increased \[18F\] FET PET uptake and measurable disease according to PET RANO 1.0.
• years or older
• Have the capacity to understand the study and be willing to comply with all protocol requirements.
• Must have an Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0-2 or KPS≥70
• Patients on stable, not increasing dose of steroids in the previous 7 days can be included in the study
• Adequate hematological, liver and renal function at the time of screening.
• Females of childbearing potential must have a negative serum pregnancy test within 7 days prior to the first dose of investigational drug product; must not be breast-feeding; and must agree to use a highly effective method of contraception during treatment and for 6 months following last dose of investigational product.
• Male patients must agree to use condoms during sex during the treatment period and for 3 months after the last dose of the investigational drug product and must not make semen donations during treatment and for 6 months following last dose of investigational drug product. For male patients with female partners of childbearing potential, females must agree to use a highly effective method of contraception during the treatment period and for 6 months following last dose of investigational drug product.

You may not qualify if:

• Prior course with external beam radiation to the brain in the past 3 months. Prior treatment with brachytherapy in the brain.
• Treatment with bevacizumab within the prior 6 weeks.
• Known contraindication to imaging tracer or any product of contrast media and MRI contraindications including implanted medical devices. Unable to lie still for at least 20 min or the duration of the MRI and PET imaging or the need for general anesthesia as part of the imaging procedure.
• History or evidence of delayed-type hypersensitivity-dependent chronic infection (ie, tuberculosis, systemic fungal or parasitic infection).
• Radiographic progression based on RANO 2.0 associated with clinical deterioration and life expectancy less than 3 months.
• Hemostaseologic conditions, precluding catheterization or invasive procedures.
• Clinically significant illness or clinically relevant trauma within 2 weeks before the administration of the investigational product.
• Known liver or kidney disease, such as hepatitis, cirrhosis, renal failure.
• Severe chronic or active infections (including active tuberculosis, hepatitis B virus, or hepatitis C virus infection) requiring systemic therapy.
• Ongoing toxicity \> Grade 2 NCI-CTCAE (version 5.0) from previous standard or investigational therapies.
• Administration of another investigational product within 90 days prior to screening.
• Expected non-compliance with longer-term admission at isolated nuclear medicine ward per regional regulations.
• Inability to complete the needed investigational and standard imaging examinations due to any reason (ie, severe claustrophobia, inability to lie still for the entire imaging time).
• Patients with known phenylketonuria.
• Presence of any other condition that may increase the risk associated with study participation or interfere with the interpretation of study results, and, in the opinion of the study investigator, would make the patient inappropriate for entry into the study.

Sponsors & Collaborators

• Telix Pharmaceuticals (Innovations) Pty Limited: lead

Study Sites (4)

Gold Coast University Hospital

Gold Coast, Queensland, Australia

RECRUITING

Austin Health

Melbourne, Australia

RECRUITING

Johannes Kepler University

Linz, Austria

RECRUITING

UMC Utrecht

Utrecht, Netherlands

RECRUITING

MeSH Terms

Conditions

Neoplasms; Glioblastoma; Brain Neoplasms; Neoplasm Recurrence, Local; Central Nervous System Neoplasms

Interventions

Lomustine

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Nitrosourea Compounds; Urea; Amides; Organic Chemicals; Nitroso Compounds

Central Study Contacts

Clinical Project Manager

CONTACT

2154902000; samuel.park@telixpharma.com

Back-up Clinical Project Manager

CONTACT

neil.smith@telixpharma.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: In the first part of the trial, cohort of patients will receive different doses of the study drug and lomustine. If the drug is not well tolerated, the dose will change in new groups of patients and additional arms of the study will open. Doctors watch closely for any serious side effects, which helps them decide when the dose is too high.

Study Record Dates

• First Submitted: July 17, 2025
• First Posted: August 3, 2025
• Study Start: November 2, 2025
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): November 1, 2027
• Last Updated: April 16, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1); AU (1)