BridgeMD
New treatment option for Glioblastoma (GBM)
Official 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
ClinicalTrials.gov ID: NCT07268053
What this study is testing
What is Risvutatug rezetecan?
Risvutatug rezetecan is an investigational medicine, given as an infusion into a vein, being studied as a potential treatment for glioblastoma (gbm).
Also referred to as HS-20093, GSK5764227.
Plain-language explanation of the investigational treatment - it is being studied and is not an approved or proven therapy. The study team can confirm the details.
- What it's testing
- 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.
- Phase 1: an early, usually small safety study
- Time commitment: about 12 months
A plain-language read of the study's public ClinicalTrials.gov listing. The study team confirms the details.
Who can take part
Ages 18 and older
You may be able to join if
- 1\. Diagnosed with: (a) GBM according to the 2021 WHO criteria, who have progressed on or following standard of care therapy, including maximal safe...
- 2\. Has archival or biopsy brain tumor tissue available.
- 3\. Has measurable disease (preoperatively) defined as at least one contrast-enhancing lesion with two perpendicular measurements of at least 1 cm.
- 4\. Age ≥18 at time of consent.
- 5\. Has a performance status of ≤2 on the ECOG scale.
You likely can't join if
- 1\. Evidence of leptomeningeal metastasis or spinal cord compression.
- 2\. Unable to undergo through MRI of the brain with IV contrast.
- 3\. Known active systemic bacterial infection (requiring IV antibiotics or fever \>38.5°C at time of initiating study treatment), fungal infection...
- 4\. Serious infections within 4 weeks prior to the first infusion of study drug, including but not limited to infectious complications, bacteremia...
- 5\. Known other concurrent severe psychiatric and/or an uncontrolled medical condition that, in the Investigator's judgement, would cause...
- 6\. Have any unresolved toxicities from prior therapy greater than NCI-CTCAE v5 Grade 1 at the time of starting study treatment (exceptions include...
See the full eligibility criteria
Who can join
- 1\. 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...
- 2\. Has archival or biopsy brain tumor tissue available.
- 3\. Has measurable disease (preoperatively) defined as at least one contrast-enhancing lesion with two perpendicular measurements of at least 1 cm.
- 4\. Age ≥18 at time of consent.
- 5\. Has a performance status of ≤2 on the ECOG scale.
- 6\. 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...
- 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...
- 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
- 7\. 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...
- 8\. For females of non-childbearing potential, is no longer of childbearing potential due to surgical, chemical, or natural menopause.
- 9\. 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...
- 10\. Agrees to adhere to Lifestyle Considerations throughout study duration.
- 11\. Able and willing to comply with scheduled visits, treatment plans, laboratory tests and other procedures.
- 12\. Understands the informed consent document and has voluntarily agreed to participate by giving written informed consent (personally or via legally authorized representative(s), and assent if applicable). Written...
What rules you out
- 1\. Evidence of leptomeningeal metastasis or spinal cord compression.
- 2\. Unable to undergo through MRI of the brain with IV contrast.
- 3\. 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...
- 4\. 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...
- 5\. 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...
- 6\. 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...
- 7\. 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...
- 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...
- 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...
- 8\. Major surgery within 4 weeks prior to the first infusion of study drug that, in the Investigator's judgement, would cause unacceptable safety risks.
- 9\. Clinically significant bleeding symptoms or significant bleeding tendency within 1 month prior to the first infusion of study drug.
- 10\. Allergy or hypersensitivity to any component of GSK5764227 (ADC, antibody, payload GSK5757810) or its excipients, history of severe allergies (e.g., anaphylactic shock), severe IRRs, or idiosyncrasy to recombinant...
- 11\. History of prior allogenic or autologous bone marrow transplant or other solid organ transplant.
- 12\. Has evidence of current ILD or pneumonitis, or history of ILD or noninfectious pneumonitis requiring high-dose glucocorticoids.
- 13\. History of moderate to severe lung disease.
- 14\. Has serious or poorly controlled hypertension including:
- a. History of hypertensive crisis.
- b. Hypertensive encephalopathy.
- c. Adjustment of antihypertensive medications due to poor blood pressure control within 2 weeks prior to the first infusion of study drug.
- d. Systolic blood pressure ≥160 mmHg or diastolic blood pressure ≥100 mmHg during screening period.
- 15\. Has any of the following cardiac examination abnormalities:
- a. Evidence of current clinically significant arrhythmias or ECG abnormalities (e.g., complete left bundle branch block, third-degree AV block, second-degree AV block, PR interval \>250 msec).
- b. Risk factors of prolonged QTc or arrhythmia events, such as: heart failure, refractory hypokalemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death of any direct relative...
- c. Has QTc \>450 msec or \>480 msec for participants with bundle branch block (QTcF can be machine-calculated or manually over-read).
- d. Known reduced LVEF fraction \<50%.
- 16\. Has severe, uncontrolled or active cardiovascular disorders, including but not limited to:
- a. Myocardial infarction within 6 months prior to first infusion of study drug.
- b. Unstable angina within 6 months prior to the first infusion of study drug, not controlled by standard of care therapy.
- c. Congestive heart failure (NYHA Class III or IV congestive heart failure) within 6 months prior to the first infusion of study drug.
- d. Cerebrovascular accident or transient ischemic attack within 6 months prior to the first infusion of study drug.
- e. History of clinically significant (as determined by the Investigator) atrial arrhythmia, not controlled by standard of care therapy.
- f. History of clinically significant (as determined by the Investigator) ventricular arrhythmia, or occurrence of any clinically significant ventricular arrhythmia during screening.
- g. Serious arteriovenous thromboembolic events (such as deep vein thrombosis, pulmonary embolism, etc.) within 3 months prior to the first infusion of study drug (except for implantable venous port, catheter-related...
- 17\. Known active infectious diseases requiring systemic treatment or known HIV. No active screening needed for active infectious diseases.
- 18\. Has documented presence HBsAg, hepatitis B core antibody (HbcAb), or hepatitis B surface antibody (HbsAb) (except for presence of HbsAb attributable to previous vaccination) at screening or within 3 months prior to...
- 19\. Has a positive HCV antibody test result at screening or within 3 months prior to the first infusion of study intervention. NOTE: Participants with a positive HCV antibody test result due to prior resolved disease...
- 20\. Has a positive HCV RNA test result at screening or within 3 months prior to the first infusion of study intervention. NOTE: The HCV RNA test is optional, and participants with a negative HCV antibody test are not...
- 21\. Has cirrhosis or current unstable livery or biliary disease (as determined by the Investigator) defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal/gastric varices, or...
- 22\. History of autoimmune disease that has required systemic treatments in the 2 years prior to screening (individuals with prior history of autoimmune disease must be discussed with the Medical Monitor; replacement...
- 23\. Has any active renal condition (e.g., requirement for dialysis, or any other significant renal condition that could affect the participant's safety [renal obstruction successfully managed by stenting is permitted]).
- 24\. Is unable to adhere to the protocol-defined Schedule of Activities, including requirements for the Follow-up Period of the study, study procedures, restrictions, and requirements as determined by the Investigator.
- 25\. Known vaccination or hypersensitivity of any level within 4 weeks prior to the first infusion of study drug.
- 26\. Has received any live vaccine within 30 days prior to the first infusion of study drug.
- 27\. Is pregnant or breastfeeding.
- 28\. Has donated blood or blood products in excess of 500 mL (approximately 1 pint) within 1 month prior to first infusion of study intervention.
The study team makes the final eligibility decision.
Where it's taking place
- Phoenix, Arizona, United States
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The study runs about 12 months per participant, based on its public description. The team confirms the exact schedule and number of visits before you enroll.
Who can join this trial?
This study is enrolling all sexes, 18 years and older. The study team makes the final eligibility decision.
Where is this trial taking place?
Study sites include Phoenix, Arizona, United States. Enter your location above to see the nearest site and check your eligibility.
Explore other conditions
BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from ClinicalTrials.gov; the study team decides eligibility.