Clinical Trial of BMS-986504 in Recurrent GBM Patients
ConditionGlioblastoma WHO Grade IV
Trial statusRecruiting
Trial phaseEarly Phase 1
Trial typeInterventional
Biological sexAll
Age18+
SponsorNader Sanai
About this trial
This is an open-label, multi-center, Phase 0/1 dose-escalation trial designed to enroll up to 12 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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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 cm.
Participants who received chemotherapy must have recovered (Common Terminology Criteria for Adverse Events [CTCAE] Grade ≤ 1) from the acute effects of chemotherapy except for residual alopecia or Grade 2 peripheral neuropathy prior to Day 1. A washout period of at least 21 days is required between the last chemotherapy dose and Day 1 (provided the participant did not receive RT).
Disqualifiers
Inability to undergo MRI brain with intravenous (IV) contrast
Known active systemic bacterial infection (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.
LVEF < 50%
History of prolonged QTc, or QT interval corrected for heart rate using Fridericia's formula (QTcF) prolongation > 480 msec, except for right bundle branch block.
Trial design
Design model
Single group
Treatments tested in this trial
BMS-986504
DrugMTA cooperative PRMT5 inhibitor
Treatment groups
12 Participants
are divided into 1 treatment groupGroup A: Recurrent WHO Grade 4 Glioblastoma MTAP loss/deletionExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
BMS-986504 Concentration in Tumor Tissue
Total and unbound BMS-986504 concentration will be quantified in Gd-enhancing and Gd-non-enhancing tumor tissue collected during Phase 0 surgery.
Time frame
intraoperative2
Number of Treatment-Emergent Adverse Events
Safety and tolerability of BMS-986504 will be assessed by tabulating (Number and Percent) Treatment-Emergent Adverse Events (TEAEs) according to the highest grade observed per participant for each event or category (per CTCAE v5.0). The analysis population includes participants who took at least one dose of the study drug.
Time frame
From date of enrollment until 30 days after last dose, assessed over 15 months3
Number of Treatment-Related Adverse Events
Safety and tolerability of BMS-986504 will be assessed by tabulating (Number and Percent) Treatment-Related Adverse Events (TEAEs) according to the highest grade observed per participant for each event or category (per CTCAE v5.0). The analysis population includes participants who took at least one dose of the study drug.
Time frame
From date of first dose of study drug until 30 days after last dose, assessed over 15 months4
Number of Serious Adverse Events
Safety and tolerability of BMS-986504 will be assessed by tabulating (Number and Percent) Serious Adverse Events (SAEs) according to the highest grade observed per participant for each event or category (per CTCAE v5.0). The analysis population includes participants who took at least one dose of the study drug.
Time frame
From date of enrollment until 30 days after last dose, assessed over 15 monthsSecondary outcomes
1
BMS-986504 Concentration in Cerebrospinal Fluid (CSF)
BMS-986504 concentration will be quantified in CSF collected during Phase 0 surgery.
Time frame
intraoperative2
6-Month Progression Free Survival (PFS6) Rate
PFS6 rate of participants that had a positive PK response and enrolled into the Expansion Phase 1 component will be quantified.
Time frame
From date of Phase 0 surgery to date of disease recurrence or death, assessed over 27 months3
Overall Survival (OS)
OS of participants that had a positive PK response and enrolled into the Expansion Phase 1 component will be summarized using Kaplan-Meier Curves and Estimates.
Time frame
From date of surgery until death, due to any cause, assessed up to 27 monthsSponsors and contacts
Click on the lead sponsor to view all of their trials.
Nader Sanai
Lead sponsor
St. Joseph's Hospital and Medical Center, Phoenix
Sponsor institution
Source ClinicalTrials.gov