Dosimetry, Safety, and Efficacy Study of [177Lu]Lu-XT771 in Patients With Recurrent Glioblastoma

Ki vehet részt

• 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
• Histologically confirmed glioblastoma (based on the 2021 WHO Classification of Tumors of the Central Nervous System, 5th edition), and confirmed CA IX/CA XII positive by histology or [68Ga]Ga-XT771 PET/CT
• Histologically confirmed recurrence of glioblastoma following prior treatments
• Suitable for Ommaya reservoir placement and meets the conditions for drug administration, as judged by the investigator
• Tumor resection cavity volume between 2.5 and 25 cm\^3
• On a stable or decreasing dose of corticosteroids (≤5 mg/day of dexamethasone or equivalent) for at least 1 week prior to the first dose
• Toxicity from prior anti-tumor treatments (e.g., chemotherapy, radiotherapy, immunotherapy) recovered to ≤ Grade 1 (excluding alopecia)
• Adequate organ and bone marrow function meeting the following criteria:; Bone marrow: Absolute neutrophil count (ANC) ≥ 1.5 ×10\^9/L and white blood cell (WBC) count ≥ 3 ×10\^9 /L (without growth factor support within 28 days prior to dosing); Platelet count ≥ 75 ×10\^9/L; Hemoglobin ≥ 90 g/L; Hepatic function: Total bilirubin ≤ 1.5 × ULN (≤ 2.0 × ULN for subjects with liver metastases; ≤ 3.0 × ULN for subjects with confirmed Gilbert's syndrome); ALT and AST ≤ 3 × ULN (< 5 × ULN for subjects with liver metastases); Albumin > 30 g/L; Renal function: Serum creatinine ≤ 1.5 × ULN and creatinine clearance rate ≥ 50 mL/min; Coagulation: INR ≤ 2.0, APTT ≤ 1.5 × ULN. (Exception: subjects receiving warfarin may have an INR between 2 and 3 inclusive)
• Fertile subjects (and their partners) must agree to use highly effective contraceptive methods (e.g., condoms, oral or injectable contraceptives) during the treatment period and for 6 months after the last dose of the study drug

Ki nem vehet részt

• 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
• Brain MRI indicating that the enhancing edge of the tumor invades the ventricular wall, or the surgical cavity communicates with the ventricle
• Known or suspected allergy to the study drug or its analogue components
• Inability to undergo contrast-enhanced MRI scans (e.g., due to pacemakers, contrast agent allergy)
• Presence of active or uncontrolled infections requiring systemic intravenous treatment, or unexplained fever >38.5°C during the screening period or before dosing
• Presence of severe coagulation disorders or evidence of significant bleeding risk; history of gastrointestinal bleeding; any Grade ≥2 bleeding event (CTCAE v5.0) within the past 6 months
• Active Hepatitis B (HBsAg positive and HBV-DNA > 500 IU/mL or above the lower limit of detection of the study center) or Active Hepatitis C (HCV antibody positive and HCV-RNA > the lower limit of detection of the study center)
• Uncontrolled hypertension as judged by the investigator (systolic blood pressure ≥ 160 mmHg and/or diastolic blood pressure ≥ 100 mmHg despite standard treatment)
• History of other uncured malignancies within the past 3 years or concurrently, except for curable in situ cancers (e.g., carcinoma in situ of the cervix, basal cell carcinoma of the skin)
• Psychiatric disorders or poor compliance
• The investigator considers the subject unsuitable for participation in this clinical study due to other severe systemic diseases or other reasons
• History of severe cardiovascular disease, such as ventricular arrhythmias requiring clinical intervention; QTc interval > 480 ms; acute coronary syndrome, congestive heart failure, stroke, or other ≥ Grade III cardiovascular events within 6 months prior to dosing; NYHA class II-IV or LVEF < 50%
• Presence of two or more intracranial lesions, extracranial metastases, or tumors located in the infratentorial compartment or basal ganglia
• Pregnant or lactating women