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

NCT07268053 | Recruiting Early Phase 1 DMC FDA Drug

• 1 other identifier: 2024-22
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

This will be an open-label Phase 0/1 study that will enroll approximately 15 participants, 9 participants with recurrent WHO Grade 4 glioma (rGBM) and 6 participants with brain metastases, who will receive the investigational drug risvutatug rezetecan (GSK5764227), a B7-H3-targeted antibody-drug conjugate (ADC) with the GSK5757810 payload. The trial will consist of a Phase 0 component (subdivided into Arms A and B) and an Expansion Phase 1 component. Participants with tumors demonstrating a positive pharmacokinetic (PK) response in the Phase 0 component will be eligible to enroll in the Expansion Phase to receive therapeutic dosing of risvutatug rezetecan.

Conditions

Glioblastoma (GBM); Brain Metastasases

Keywords

ADC; Antibody Drug Conjugate

Outcome Measures

Primary Outcomes (2)

• Phase 0: Total, Cleaved, and Unbound GSK5757810 Payload Concentration in Tumor Tissue

  The total, cleaved, and unbound GSK5757810 payload concentration in Gd enhancing and Gd non-enhancing tumor tissue collected during Phase 0 surgery from participants with rGBM, and Gd enhancing tumor tissue collected during Phase 0 surgery from participants with brain metastases, will be determined.

  Intraoperatively

• Phase 1: Incidence of Adverse Events as Assessed by CTCAE v5.0

  Incidence of the following will be summarized: AEs, SAEs, and AEs of Special Interest (AESIs); treatment discontinuations, dose interruptions, and dose reductions due to AEs; changes in vital signs, body weight, laboratory tests, ECG, and ECOG performance status

  Date of first infusion until 90-days post last infusion

Secondary Outcomes (4)

• Phase 0: Total, Cleaved, and Unbound GSK5757810 Payload Concentration in CSF

  Intraoperatively

• Phase 0: pH2AX and B7-H3 Expression Change in Tumor Tissue

  Intraoperatively, archival

• Phase 1: Progression-Free Survival at 6 Months (PFS6)

  Date of first infusion to the date of disease recurrence or death due to any cause (whichever occurs first), assessed up to 6 months

• Phase 1: Overall Survival (OS)

  Date of first infusion to the date of death due to any cause, assessed up to 24 months

Study Arms (1)

rGBM and Brain Mets

EXPERIMENTAL

Group A will include participants with recurrent WHO Grade 4 glioma (rGBM) and group B will include participants with brain metastases (brain mets)

Drug: Risvutatug rezetecan

Interventions

Risvutatug rezetecan DRUG

Risvutatug rezetecan will be administered intravenously.

Also known as: HS-20093, GSK5764227

rGBM and Brain Mets

Eligibility Criteria

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

You may qualify if:

• \. Diagnosed with: (a) GBM according to the 2021 WHO criteria, who have progressed on or following standard of care therapy, including maximal safe resection (biopsy allowed if resection was deemed unsafe) and concurrent chemoradiation; OR (b) Brain metastasis requiring surgical resection, whether treated or untreated, and must have well-controlled systemic disease or NED other than the brain metastases, in the opinion of the patient's primary oncologist.
• \. Has archival or biopsy brain tumor tissue available.
• \. Has measurable disease (preoperatively) defined as at least one contrast-enhancing lesion with two perpendicular measurements of at least 1 cm.
• \. Age ≥18 at time of consent.
• \. Has a performance status of ≤2 on the ECOG scale.
• \. Has adequate bone marrow and organ function as defined by the following laboratory values (as assessed by the local laboratory for eligibility):
• Adequate Bone Marrow Function: Absolute neutrophil count ≥1500/μL (≥1.5 x 109/L), Platelets (at time of surgery) ≥100,000/μL (≥100 x 109/L), Hemoglobin ≥9.0 g/dL or ≥5.6 mmol/L (Criteria must be met without erythropoietin dependency and without pRBC transfusion within prior 2 weeks.)
• Adequate Hepatic Function: Total Bilirubin ≤1.5x ULN (Participants with Gilbert's syndrome with a total bilirubin \>1.5x ULN and direct bilirubin ≤1.5x ULN will be permitted.), AST (SGOT) ≤2.5x institutional ULN, ALT (SGPT) ≤2.5x institutional ULN (Participants with liver metastases with ALT ≤5x ULN will be permitted.)
• Adequate Renal Function: eGFR ≥50 mL/min/1.73 m2 (Calculated as individualized eGFR using the CKD-EPI formula \[2021\]); If measured or calculated GFR (e.g., creatinine clearance; mGFR) is required or used: ≥60 mL/min
• Adequate Metabolic Function: Albumin ≥2.8 g/dL
• Adequate Coagulation: INR or PT and aPTT ≤1.5x ULN
• \. For females of childbearing potential: (a) Must have a confirmed negative serum pregnancy test (β-hCG) before starting study treatment (within 24 hours of first infusion); in rare cases where hCG is suspected to be elevated in the absence of pregnancy (e.g., due to a tumor producing hCG), an ultrasound must be performed to rule out possible pregnancy. (b) Must use a highly effective method of contraception (with a failure rate of \<1% per year and low user dependency) for at least 28 days prior to treatment, and agree to use such a method during study participation and for an additional 8 months after final study drug administration. (c) Agrees not to breastfeed starting at screening, during study participation, and for 8 months after final study drug administration. (d) Agrees not to donate eggs (ova, oocytes) for the purpose of reproduction starting at screening, during study participation, and for 8 months after final study drug administration.
• \. For females of non-childbearing potential, is no longer of childbearing potential due to surgical, chemical, or natural menopause.
• \. For males: (a) Agrees not to donate sperm starting at screening, during study participation, and for 5 months after final study drug administration. (b) Abstains from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agrees to remain abstinent starting at screening, during study participation, and for 5 months after final study drug administration; OR Must use a male condom and their female partner must use an additional highly effective method of contraception (with a failure rate of \<1% per year and low user dependency) starting at screening, during study participation, and for 5 months after final study drug administration.
• \. Agrees to adhere to Lifestyle Considerations throughout study duration.

You may not qualify if:

• \. Evidence of leptomeningeal metastasis or spinal cord compression.
• \. Unable to undergo through MRI of the brain with IV contrast.
• \. Known active systemic bacterial infection (requiring IV antibiotics or fever \>38.5°C at time of initiating study treatment), fungal infection, or detectable viral infection (such as known human immunodeficiency virus positivity or with known active hepatitis B or C \[for example, hepatitis B surface antigen positive\] (screening of viral infection is not required for enrollment).
• \. Serious infections within 4 weeks prior to the first infusion of study drug, including but not limited to infectious complications, bacteremia, severe pneumonia treated with IV antibiotics for ≥2 weeks; active infections with therapeutic IV antibiotics within 2 weeks prior to the first infusion of study drug. (Individuals who are receiving or have received prophylactic antibiotics \[e.g., prophylaxis against urinary infections\] are allowed).
• \. Known other concurrent severe psychiatric and/or an uncontrolled medical condition that, in the Investigator's judgement, would cause unacceptable safety risks, contraindicate participation in the clinical study, or compromise compliance with the protocol.
• \. Have any unresolved toxicities from prior therapy greater than NCI-CTCAE v5 Grade 1 at the time of starting study treatment (exceptions include: alopecia, hearing loss, vitiligo, endocrinopathy managed with replacement therapy, Grade 2 neuropathy, and any chronic Grade 2 toxicities following discussion with the Principal Investigator).
• \. Has received treatment with any of the following:
• a. Orlotamab, enoblituzumab, I-Dxd, or otherB7-H3 targeted agents.
• b. Investigational agent within 4 weeks prior to the first infusion of study drug.
• c. Cytotoxic chemotherapy or anticancer drugs within 14 days prior to the first infusion of study drug.
• d. Monoclonal antibody within 28 days prior to the first infusion of study drug.
• e. Immunosuppressive agents within 30 days prior to the first infusion of study drug, or requires long-term (30 days or longer) glucocorticoid therapy. NOTE: A stable or reduced daily dose of 8 mg dexamethasone for management of GBM-related edema and its associated symptoms within 14 days prior to dosing is permitted; however, additional weekly CBC monitoring is required during concomitant administration of dexamethasone with GSK5764227, as outlined in the SoA (see section 1.3). NOTE: Low dose corticosteroids (prednisone ≤10 mg/day or equivalent) may be administered and use of inhaled or topical steroids and prophylactic corticosteroids for procedures are permitted.
• f. Strong/moderate inhibitors of CYP3A4, CYP2D6, P-gp, or BCRP, within 7 days prior to the first infusion of study drug; or need to continue treatment with these drugs (should be discontinued for at least 14 days prior to the first study infusion).
• g. Transfusion of blood products (including platelets or red blood cells) or administration of colony-stimulating factors (including G-CSF, granulocyte-macrophage colony-stimulating factor, or recombinant erythropoietin) with 14 days prior to enrollment.
• \. Major surgery within 4 weeks prior to the first infusion of study drug that, in the Investigator's judgement, would cause unacceptable safety risks.

Sponsors & Collaborators

• Nader Sanai: lead
• GlaxoSmithKline: collaborator

Study Sites (1)

St. Joseph's Hospital and Medical Center

Phoenix, Arizona, 85013, United States

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

• Nader Sanai, MD

  Ivy Brain Tumor Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Phase 0 Navigator

CONTACT

602-406-8605; research@ivybraintumorcenter.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: SPONSOR INVESTIGATOR
• PI Title: Director, Ivy Brain Tumor Center

Study Record Dates

• First Submitted: November 24, 2025
• First Posted: December 5, 2025
• Study Start: February 11, 2026
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): July 1, 2029
• Last Updated: March 6, 2026

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)