Actively Recruiting
A Phase 0/1 Trial of GSK5764227, a B7-H3-Targeted Antibody-Drug Conjugate, in Patients With Recurrent Grade 4 Glioma and Brain Metastases
Led by Nader Sanai · Updated on 2026-03-06
15
Participants Needed
1
Research Sites
104 weeks
Total Duration
On this page
Sponsors
N
Nader Sanai
Lead Sponsor
G
GlaxoSmithKline
Collaborating Sponsor
AI-Summary
What this Trial Is About
Researchers are evaluating risvutatug rezetecan, a B7-H3-targeted antibody-drug conjugate (ADC), in an open-label Phase 0/1 clinical trial involving about 15 participants. The study includes patients with recurrent WHO Grade 4 glioma (rGBM) and brain metastases. The trial aims to assess pharmacokinetics (PK), pharmacodynamics (PD), and safety of this investigational drug to better understand its effects in these brain tumor conditions. In Phase 0, participants with rGBM enter Arm A to establish the optimal time interval (OTI) for surgery after drug infusion, based on PK data. Arm A has two cohorts: Cohort 1 determines OTI, and Cohort 2 receives the drug infusion at that OTI. Patients with brain metastases enroll in Arm B and receive the infusion at the same OTI. Only participants with positive PK response in Phase 0 proceed to Phase 1 expansion. In Phase 1, these participants receive risvutatug rezetecan intravenously every three weeks after surgery recovery, continuing until disease progression or other stopping criteria. Participants undergo multiple assessments including blood, serum, cerebrospinal fluid, and tumor tissue collection during surgery to evaluate drug concentration and biological response. Safety is monitored through routine visits, with follow-ups at 30, 60, and 90 days post-treatment, and survival monitored up to 12 months. MRI scans are performed every 2-3 months to track disease status. Overall participation lasts about 15 months post last infusion, encompassing screening, treatment, follow-up, and survival monitoring periods.
CONDITIONS
Brief Title
A Phase 0/1 Clinical Trial With an Expansion Phase of GSK5764227, a B7-H3-Targeted Antibody-Drug Conjugate (ADC), in Patients With Recurrent Grade 4 Glioma and Patients With Brain Metastases
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Diagnosed with Grade 4 glioma (GBM) per 2021 WHO criteria after standard therapy progression, or brain metastasis requiring surgical resection with well-controlled systemic disease.
- Has available archival or biopsy brain tumor tissue.
- Has measurable disease with at least one lesion ≥1 cm before surgery.
- Age 18 years or older at consent.
- Performance status of 2 or less on the ECOG scale.
- Adequate bone marrow, liver, kidney, metabolic, and coagulation function as defined by specific laboratory values.
- For females of childbearing potential: negative pregnancy test, use of highly effective contraception, no breastfeeding, and no egg donation during and for 8 months after study drug administration.
- For females of non-childbearing potential: confirmed no longer of childbearing potential.
- For males: agreement to avoid sperm donation and use contraception or abstain from heterosexual intercourse during and for 5 months after study drug administration.
- Willingness to follow lifestyle considerations and comply with study visits, treatments, and procedures.
- Understands and voluntarily consents to participate.
You will not qualify if you...
- Evidence of leptomeningeal metastasis or spinal cord compression.
- Unable to have MRI of the brain with IV contrast.
- Active systemic bacterial, fungal, or viral infection requiring treatment.
- Serious infections within 4 weeks before study drug infusion.
- Severe psychiatric or uncontrolled medical conditions posing safety risks or affecting protocol compliance.
- Unresolved toxicities from prior therapy greater than Grade 1, with some exceptions.
- Prior treatment with certain B7-H3 targeted agents, investigational drugs, chemotherapy, monoclonal antibodies, immunosuppressants, or interacting medications within specified timeframes.
- Recent blood transfusions or colony-stimulating factors use within 14 days prior.
- Major surgery within 4 weeks before study drug infusion.
- Significant bleeding disorders within 1 month before study drug infusion.
- Allergy or hypersensitivity to the study drug or components.
- History of bone marrow or solid organ transplant.
- Current or history of interstitial lung disease or pneumonitis requiring high-dose steroids.
- Moderate to severe lung disease.
- Serious or uncontrolled hypertension.
- Cardiac abnormalities or significant arrhythmias.
- Severe or uncontrolled cardiovascular disorders within 6 months prior.
- Known active infectious diseases requiring treatment or known HIV.
- Positive hepatitis B or C tests unless resolved.
- Liver cirrhosis or unstable liver disease.
- Autoimmune disease requiring systemic treatment in past 2 years.
- Active significant renal conditions.
- Unable to follow study schedule or procedures.
- Recent vaccination or live vaccine within 30 days.
- Pregnancy or breastfeeding.
- Recent blood donation exceeding 500 mL within 1 month prior to study drug infusion.
AI-Screening
AI-Powered Screening
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Your Study Journey
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person)
Duration - Up to approximately 2 months
Participants receive an intravenous infusion of risvutatug rezetecan and undergo surgery to assess drug concentration and pharmacodynamics in tumor tissue.
Multiple visits including dosing, surgery, and post-operative follow-up
Duration - Variable, until disease progression or discontinuation
Participants with positive pharmacokinetic response continue to receive risvutatug rezetecan intravenously every three weeks until disease progression, unacceptable toxicity, withdrawal, or study end.
Infusions every 3 weeks with assessments per treatment cycle
Duration - 90 days post last infusion
Participants complete safety follow-up visits after treatment discontinuation to monitor adverse events and overall safety.
3 visits (30-day, 60-day, and 90-day post-treatment follow-ups)
Duration - Up to 12 months
Participants are monitored for survival with clinic contacts approximately every 3 months for up to 12 months following safety follow-up visits. MRI scans occur approximately every 2-3 months per standard of care to monitor disease progression.
Quarterly visits or contacts for survival data collection and MRI scans per standard care
Trial Site Locations
Total: 1 location
1
St. Joseph's Hospital and Medical Center
Phoenix, Arizona, United States, 85013
Actively Recruiting
Research Team
P
Phase 0 Navigator
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NA
Model
SINGLE_GROUP
Primary Purpose
TREATMENT
Number of Arms
1
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