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

NCT07648823 | Recruiting Early Phase 1

• 1 other identifier: HX-A-2026029C
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Recurrent Glioblastoma (WHO-Grade IV Glioma); Recurrent Glioblastoma; Glioblastoma (GBM); Recurrent Glioblastoma IDH Wildtype

Keywords

Recurrent Glioblastoma; [177Lu]Lu-XT771; Carbonic Anhydrase IX; Carbonic Anhydrase XII; Safety and Tolerability; Dosimetry; Efficacy

Outcome Measures

Primary Outcomes (2)

• 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.

  30 minutes, 2 hours, 24 hours, 48 hours, 72 hours, and 5-7 days post-injection

• Safety and Tolerability

  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.

  From the time of informed consent up to 30 days after the last dose

Secondary Outcomes (1)

• Progression-Free Survival (PFS)

  Every 8 weeks from the date of injection until disease progression or completion of 1 year of follow-up, whichever occurs first.

Study Arms (1)

[177Lu]Lu-XT771

EXPERIMENTAL

All eligible participants with recurrence of glioblastoma will be assigned to this single experimental arm. Participants will receive a single-dose locoregional injection of 3-5 mCi of the investigational radiopharmaceutical, \[177Lu\]Lu-XT771. The drug will be administered directly into the tumor resection cavity via a surgically implanted Ommaya reservoir. Prior to the therapeutic injection, a leakage test using a \[68Ga\]Ga-XT771 tracer (4-6 mCi) will be performed to ensure proper reservoir function and safety. Additionally, to prevent cerebral edema, participants will receive a prophylactic course of oral dexamethasone (4 mg, 3 times daily), starting 24 hours prior to the \[177Lu\]Lu-XT771 injection and continuing for a total of 4 days. Following the administration, participants will be isolated until radioactivity levels reach safe discharge standards and will undergo serial SPECT/CT imaging for radiation dosimetry assessments.

Drug: [177Lu]Lu-XT771

Interventions

[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.

[177Lu]Lu-XT771

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.
• 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 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%.
• 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).
• Presence of two or more intracranial lesions, extracranial metastases, or tumors located in the infratentorial compartment or basal ganglia.
• Brain MRI indicating that the enhancing edge of the tumor invades the ventricular wall, or the surgical cavity communicates with the ventricle.
• Psychiatric disorders or poor compliance.
• Pregnant or lactating women.

Sponsors & Collaborators

• Beijing Tiantan Hospital: lead

Study Sites (2)

Beijing Tiantan Hospital, Capital Medical University

Beijing, Beijing Municipality, 100070, China

RECRUITING

Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College

Beijing, Beijing Municipality, 100730, China

RECRUITING

MeSH Terms

Conditions

Glioblastoma

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Study Officials

• Deling Li, M.D.

  Beijing Tiantan Hospital

  PRINCIPAL INVESTIGATOR

• Zhaohui Zhu, M.D.

  Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Li'ao Wang, M.D.

CONTACT

+86 15001171671; wangliao17@163.com

Deling Li, M.D.

CONTACT

lideling@bjtth.org

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Vice President

Study Record Dates

• First Submitted: June 10, 2026
• First Posted: June 15, 2026
• Study Start (Estimated): June 20, 2026
• Primary Completion (Estimated): June 20, 2027
• Study Completion (Estimated): June 1, 2028
• Last Updated: June 15, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

CN (2)