The primary objective of this study is to evaluate the dosimetry, safety, and tolerability of the investigational radiopharmaceutical \[177Lu\]Lu-XT771 in patients with recurrent glioblastoma, an aggressive form of brain cancer. \[177Lu\]Lu-XT771 is designed to specifically target and deliver beta radiation directly to tumor cells that overexpress carbonic anhydrase IX and XII (CA IX and CA XII).
This early-phase, investigator-initiated trial will enroll a small group of approximately 3-5 patients, each receiving a single dose of \[177Lu\]Lu-XT771. The drug will be administered locoregionally via an implanted Ommaya reservoir, directly into the tumor cavity. Following administration, patients will be closely monitored using single-photon emission computed tomography/computed tomography (SPECT/CT) to assess the biodistribution of the drug and to quantify the absorbed radiation dose to both the tumor and normal organs.
The study will also document all adverse events to characterize the safety profile of the treatment and will provide a preliminary assessment of its anti-tumor activity, as measured by progression-free survival. The information gathered from this exploratory study will be used to determine the recommended safe starting dose for future Phase I clinical trials.
Subject has fully understood the study and voluntarily signed the informed consent form.
Age ≥ 18 and ≤ 80 years old.
Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 1.
Life expectancy of at least 3 months.
Received anti-tumor treatments (including radiotherapy, chemotherapy, biological therapy, endocrine therapy, targeted therapy, etc.) within 4 weeks prior to dosing. Exceptions: (1) immunotherapy, nitrosoureas, or mitomycin C within 6 weeks prior to dosing; (2) oral fluorouracils and small molecule targeted drugs within 2 weeks or 5 half-lives (whichever is longer) prior to dosing; (3) Traditional Chinese Medicine with anti-tumor indication within 2 weeks prior to dosing; (4) cranial radiotherapy within 3 months prior to dosing.
Received any other unapproved investigational drug within 4 weeks prior to dosing.
Underwent major organ surgery (excluding needle biopsy) or experienced significant trauma within 4 weeks prior to dosing, or expected to require elective surgery during the study period.
Known or suspected allergy to the study drug or its analogue components.
Single group
[177Lu]Lu-XT771
Drug\[177Lu\]Lu-XT771 is a novel, first-in-human radiopharmaceutical designed to specifically target Carbonic Anhydrase IX (CA IX) and XII (CA XII), which are overexpressed in the glioblastoma microenvironment. Unlike systemic intravenous therapies, this intervention utilizes a highly localized delivery method: a single dose of 3-5 mCi \[177Lu\]Lu-XT771 is injected directly into the tumor resection cavity via a surgically implanted Ommaya reservoir. To ensure precise safety, two specific steps are required: 1) A mandatory pre-treatment leakage test using a \[68Ga\]Ga-XT771 tracer (4-6 mCi) with PET/CT imaging to rule out any leakage into the subcutaneous or subarachnoid spaces; and 2) The extraction of an equivalent volume of cerebrospinal fluid immediately prior to the therapeutic injection. Furthermore, to mitigate radiation-induced cerebral edema, the intervention is paired with a prophylactic regimen of oral dexamethasone (4 mg, three times daily) for 4 days.
Radiation Dosimetry
To evaluate the radiation dosimetry and biodistribution of a single locoregional injection of \[177Lu\]Lu-XT771. It will be quantified using serial whole-body planar scintigraphy and SPECT/CT imaging to measure drug distribution and calculate the cumulative radiation absorbed dose in the tumor cavity and critical normal organs (e.g., kidneys). These dosimetric data will be used to determine the recommended starting dose for future Phase I trials.
Incidence and severity of adverse events and incidence of serious adverse events
Safety and tolerability will be evaluated by monitoring the incidence and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs). All AEs will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. Assessments include patient complaints, vital signs, physical examinations, 12-lead ECGs, and clinical laboratory abnormalities.
Progression-Free Survival (PFS)
PFS is defined as the time from the date of \[177Lu\]Lu-XT771 administration until the first date of objectively documented radiographic disease progression or death from any cause. Tumor response and progression will be assessed using contrast-enhanced head MRI based on the Response Assessment in Neuro-Oncology (RANO) 2.0 criteria.
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