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
Nader Sanai
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.
Description
Phase 0: Patients with rGBM will enroll into Arm A. Arm A Cohort 1 will determine the optimal time interval (OTI) for surgery based on PK data assessed from two sub-cohorts (Cohort 1a and 1b). The OTI will be defined as the surgical time interval after dosing that corresponds to the highest median concentration of unbound risvutatug rezetecan payload in gadolinium (Gd) non enhancing rGBM tissue in either Cohort 1a or Cohort 1b. Arm A Cohort 2 will receive the IV infusion at the OTI schedule. Cohort 2 enrollment will begin once Arm A Cohort 1 enrollment is complete and the OTI has been determ…
Eligibility
- Age range
- 18+ years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: * 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 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. * 2\. Has archival or biopsy brain tumor tissue available. * 3\. Has measurable disease (preoperatively) defined as…
Interventions
- DrugRisvutatug rezetecan
Risvutatug rezetecan will be administered intravenously.
Location
- St. Joseph's Hospital and Medical CenterPhoenix, Arizona