A Global, Multicenter, Prospective, Controlled, Open-Label Pivotal Study of Iodofalan (131I) Solution for Injection (TLX101-Tx) Plus Lomustine Versus Lomustine Alone in Patients With Radiographically Confirmed Recurrent Glioblastoma at First Recurrence (IPAX BrIGHT [IPAX-3])
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.
• 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.
• 18 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.