A Phase 0/1 Study of BMS-986504, a MTA Cooperative PRMT5 Inhibitor in Recurrent Glioblastoma Participants With MTAP Deleted Tumors Scheduled for Resection to Evaluate Central Nervous System (CNS) Penetration With PK-Triggered Expansion Cohort
Nader Sanai
Summary
This is an open-label, multi-center, Phase 0/1 dose-escalation trial designed to enroll up to 9 total recurrent glioblastoma (rGBM) participants with confirmed MTAP loss/deletion in their archival or pretreatment biopsy tissue, who are scheduled for surgical resection. MTAP loss/deletion will be determined by next-generation sequencing (NGS). The trial will include a dose escalation design to evaluate the pharmacokinetics (PK) and safety and tolerability of BMS-986504 (MRTX1719). The trial will be composed of a Phase 0 component and an Expansion Phase 1 component. Participants with tumors demonstrating a positive PK response in the Phase 0 component of the study will be eligible to enroll into the the Phase 1 component that will include 21-day cycles of therapeutic dosing of BMS-986504.
Description
PHASE 0 Eligible participants will enroll in the Phase 0 study and receive BMS-986504 in three dose escalation cohorts over 6 days prior to surgical resection. The final dose will be administered 3-5 hours before tumor resection on Day 6. Participants without histologically confirmed diagnosis of recurrent GBM after the craniotomy will be replaced. Phase 0 Dose Escalation An initial cohort of three participants will be enrolled at the starting dose level. If ≤1 of the participants experiences a dose-limiting toxicity (DLT) through the end of the Phase 0, the dose is escalated to the next le…
Eligibility
- Age range
- 18+ years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: * Participants with the diagnosis of glioblastoma by the 2021 WHO criteria, who have progressed on or following previous tumor-directed therapy, which must have included a maximal safe resection (biopsy allowed if it was deemed unsafe to resect) and fractionated radiotherapy (RT). * Patients with archival tissue demonstrating MTAP loss/deletion confirmed through NGS will be qualified for Phase 0 portion of the study. * Participants must have measurable disease preoperatively, defined as at least 1 contrast-enhancing lesion, with 2 perpendicular measurements of at least 1 c…
Interventions
- DrugBMS-986504
MTA cooperative PRMT5 inhibitor
Location
- St. Joseph's Hospital and Medical CenterPhoenix, Arizona