A Phase III Study of TLX101-Tx Plus Standard of Care (SoC) Versus SoC Alone for the Treatment of Patients with Recurrent Glioblastoma

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Telix Pharmaceuticals (Innovations) Pty Limited

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

4 Mar 2026 → ongoing

Decision date (initial)

2025-10-13

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Telix Pharmaceuticals (Innovations) Pty Ltd

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Dose response, Safety, Others

Part 1 Safety and Dosimetry Lead-in: Part 1a BOIN: Dose optimization and determine the RP3D. To determine the MTD and recommended dose of TLX101-Tx plus lomustine (or TLX101-Tx as a monotherapy) for the safety dose-expansion Part 1b.

Part 1b Dose Expansion Cohort: To determine the safety, tolerability, and the recommended Phase 3 study dose of TLX101-Tx in combination with lomustine (or TLX101-Tx as a monotherapy) in patients with confirmed first recurrence of glioblastoma.

Part 2 Randomized Study: To evaluate whether TLX101-Tx concomitant with lomustine (or TLX101-Tx monotherapy based on the totality of data from Part 1) improves overall survival (OS) compared to lomustine alone.

Secondary objectives 8

1. Part 1 Safety and Dosimetry Lead-In: Part 1a and 1b: To determine tumor and normal organ radiation dosimetry for TLX101-Tx in confirmed recurrent glioblastoma patients.
2. Part 1a and 1b:To characterize the PK and the urinary excretion of TLX101-Tx.
3. Part 1a BOIN: To determine the safety and tolerability of TLX101-Tx in combination with lomustine (or TLX101-Tx as a monotherapy) in patients with confirmed first recurrence of glioblastoma.
4. Part 1b Dose Expansion Cohort: To determine preliminary efficacy for the MTD treatment regimen.
5. Part 1b Dose Expansion Cohort: To determine the response rate at the MTD.
6. Part 2 Randomized Study: To evaluate whether TLX101-Tx concomitant with lomustine (or as TLX101-Tx monotherapy) improves PFS of patients compared to lomustine alone.
7. Part 2 Randomized Study: To assess Health Related Quality of Life of patients treated with TLX101-Tx plus lomustine or TLX101-Tx monotherapy.
8. Part 2 Randomized Study: To assess safety and tolerability.

Conditions and MedDRA coding

Glioblastoma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. Previously confirmed neuropathological diagnosis of glioblastoma, IDH-wildtype according to the WHO 2021 classification.
2. 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: a. Any systemic antineoplastic treatment other than nitroureas b. Tumor-treating fields c. Conventionally fractionated or abbreviated (minimum 15 fractions) radiotherapy.
3. 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, with a TBRmax ≥2.3, as determined by central review.
4. Tumor debulking for recurrent, progressive disease is allowed. The patient must have post-surgical (4-6weeks) radiographic evidence for residual tumor according to RANO 2.0 with increased [18F]FET PET uptake (TBRmax ≥2.3) and measurable disease according to PET RANO 1.0.
5. Male or female ≥18 years of age.
6. Have the capacity to understand the study and be willing to comply with all protocol requirements.
7. Must have an Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0–2 or KPS≥70.
8. Patients on stable, not increasing dose of steroids in the previous 7 days can be included in the study.
9. Adequate hematological, liver and renal function at the time of screening. a) Bone marrow: i. Platelets ≥100×109/L. ii. Absolute neutrophil count ≥1.5×109/L. iii. Hemoglobin >10g/dL (with no red blood cell transfusion in the previous 4 weeks).b) Liver function:i. Total bilirubin ≤1.5× the upper limit of normal (ULN). ii. Total bilirubin ≤3 × ULN with patients with Gilbert’s Syndrome. ii. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤5 × ULN with patients with known liver metastases. iii. c) Renal function: i. Creatinine clearance ≥ 60 mL/min determined using the European Kidney Function Consortium (EKFC) formula (see Appendix 4).
10. 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.
11. 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.

Exclusion criteria 15

1. Prior course with external beam radiation to the brain in the past 3 months. Prior treatment with brachytherapy in the brain.
2. Treatment with bevacizumab within the prior 6 weeks.
3. 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.
4. History or evidence of delayed-type hypersensitivity-dependent chronic infection (ie, tuberculosis, systemic fungal or parasitic infection).
5. Radiographic progression based on RANO 2.0 associated with clinical deterioration and life expectancy less than 3 months.
6. Hemostaseologic conditions, precluding catheterization or invasive procedures.
7. Clinically significant illness or clinically relevant trauma within 2 weeks before the administration of the investigational product.
8. Known liver or kidney disease, such as hepatitis, cirrhosis, renal failure.
9. Severe chronic or active infections (including active tuberculosis, hepatitis B virus, or hepatitis C virus infection) requiring systemic therapy.
10. Ongoing toxicity > Grade 2 NCI-CTCAE (version 5.0) from previous standard or investigational therapies.
11. Administration of another investigational product within 90 days prior to screening.
12. Expected non-compliance with longer-term admission at isolated nuclear medicine ward per regional regulations.
13. 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).
14. Patients with known phenylketonuria.
15. 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. Part 1 Safety and Dosimetry Lead-in: Part 1a BOIN: Assessment of TEAEs type as described as dose-limiting, frequency, severity according to NCI CTCAE v5.0.
2. Part 1 Safety and Dosimetry Lead-in: Part 1b Dose Expansion Cohort: Safety assessments include physical examination, vital signs, ECG abnormalities, clinical laboratory assessments, adverse events reported according to the NCI CTCAE v5.0. Tolerability as assessed by HRQoL total scores on European Organization for Research and Treatment of Cancer – EORTC QLQ-C30 and EORTC-BN20 questionnaires, neurological symptoms assessed with the NANO scale.
3. Part 2 Randomized Study: OS determined from the date of enrollment until death from any cause.

Secondary endpoints 8

1. Part 1 Safety and Dosimetry Lead-In: Part 1a and 1b:Absorbed radiation doses based on quantitative imaging (expressed as mGy/MBq of administered TLX101-Tx) to tumor and bone marrow, using SPECT imaging. The planar images of the head and tumor volume estimates from CT/MRI will be used to obtain an estimate of the tumor dose per administered activity of 131I.
2. Part 1a and 1b: Time course of the radioactivity and of TLX101 in blood and cumulative urine excretion of the radioactivity after administration of TLX101-Tx Blood and urine PK parameters of TLX101-Tx, PK/PD modeling will be performed using venous blood samples and if data allows, exposure-response analyses will be performed to correlate blood PK metrics and/or tumor and organ absorbed doses to efficacy and safety endpoints.
3. Part 1a BOIN: Safety assessments include physical examination, vital signs, ECG abnormalities, clinical laboratory assessments, adverse events reported according to the NCI CTCAE v5.0. Tolerability as assessed by HRQoL total scores on European Organization for Research and Treatment of Cancer – EORTC QLQ-C30 and EORTC-BN20 questionnaires, neurological symptoms assessed with the NANO scale.
4. Part 1b Dose Expansion Cohort: PFS from the time of enrollment as assessed by central core lab using RANO 2.0 or death due to any cause (whichever occurs first).
5. Part 1b Dose Expansion Cohort: Objective response rate assessed by the central core lab according to RANO 2.0.
6. Part 2 Randomized Study: PFS from the date of enrollment randomization per RANO 2.0 criteria as assessed by the central core lab or death due to any cause (whichever occurs first).
7. Part 2 Randomized Study: Tolerability as assessed by HRQoL total scores on European Organization for Research and Treatment of Cancer – EORTC QLQ-C30 and EORTC-BN20 questionnaires.
8. Part 2 Randomized Study: Safety assessments include physical examination, vital signs, and clinical laboratory assessments as well as adverse events reported according to the NCI CTCAE v5.0.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 1

Auxiliary 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Telix Pharmaceuticals (Innovations) Pty Limited

Sponsor organisation

Telix Pharmaceuticals (Innovations) Pty Limited

Address

55 Flemington Road

City

North Melbourne

Postcode

3051

Country

Australia

Scientific contact point

Organisation

Telix Pharmaceuticals (Innovations) Pty Limited

Contact name

Global Clinical Operations

Public contact point

Organisation

Telix Pharmaceuticals (Innovations) Pty Limited

Contact name

Corporate Communications

Third parties 4

Locations

3 EU/EEA countries · 8 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 39 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

5 submissions — initial application plus substantial / non-substantial modifications