Clinical Trial of BMS-986504 in Recurrent GBM Patients

NCT06883747 | Recruiting Early Phase 1 DMC FDA Drug

• 1 other identifier: 2024-21
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Glioblastoma WHO Grade IV

Keywords

MTAP loss; MTAP deletion; MTAP del

Outcome Measures

Primary Outcomes (6)

• 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.

  intraoperative

• 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.

  From date of enrollment until 30 days after last dose, assessed over 15 months

• 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.

  From date of first dose of study drug until 30 days after last dose, assessed over 15 months

• 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.

  From date of enrollment until 30 days after last dose, assessed over 15 months

• Number of Clinical Laboratory Abnormalities

  Safety and tolerability of BMS-986504 will be assessed by tabulating (Number and Percent) Clinical Laboratory Abnormalities 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.

  From date of enrollment until 30 days after last dose, assessed over 15 months

• Number of Drug-Related Toxicities

  Safety and tolerability of BMS-986504 will be assessed by tabulating (Number and Percent) Drug-Related Toxicities (defined by Dose Limiting Toxicities) 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.

  From date of first dose of study drug until 30 days after last dose, assessed over 15 months

Secondary Outcomes (3)

• BMS-986504 Concentration in Cerebrospinal Fluid (CSF)

  intraoperative

• 6-Month Progression Free Survival (PFS6) Rate

  From date of Phase 0 surgery to date of disease recurrence or death, assessed over 27 months

• Overall Survival (OS)

  From date of surgery until death, due to any cause, assessed up to 27 months

Study Arms (1)

Recurrent WHO Grade 4 Glioblastoma MTAP loss/deletion

EXPERIMENTAL

Drug: BMS-986504

Interventions

BMS-986504 DRUG

MTA cooperative PRMT5 inhibitor

Also known as: MRTX1719

Recurrent WHO Grade 4 Glioblastoma MTAP loss/deletion

Eligibility Criteria

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

You may qualify if:

• 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).
• Age ≥ 18 at time of consent
• Have a performance status (PS) of ≤ 2 on the Eastern Cooperative Oncology Group (ECOG) scale
• Participant 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 ≥ 1,500/mcL; Platelets (at time of surgery) ≥ 100,000/mcL; Hemoglobin ≥ 9.0 g/dL (participants may receive erythrocyte transfusions to achieve this hemoglobin level at the discretion of the investigator. Initial treatment must not begin earlier than the day after the erythrocyte transfusion.)
• Adequate Hepatic Function: Total Bilirubin ≤ 1.5 X ULN; Participants with Gilbert's syndrome with a total bilirubin ≤ 2.0 times ULN and direct bilirubin within normal limits are permitted; AST (SGOT) ≤ 3 X institutional ULN; ALT (SGPT) ≤ 3 X institutional ULN
• Adequate Renal Function: Estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73 m2 by Chronic Disease Epidemiology Collaboration (CKD-EPI) equation; Serum creatinine ≤ 1.5 X ULN or estimated creatinine clearance \>/= 60 mL/min (calculated using Institutional standard method)
• Coagulation Function: INR ≤ 1.5 X ULN
• Ability to swallow oral medications without crushing or chewing.
• Confirmed negative serum pregnancy test (β-hCG) before starting study treatment or participant who is no longer of childbearing potential due to surgical, chemical, or natural menopause.
• For females of reproductive potential: use of highly effective contraception for at least 28 days prior to treatment and agreement to use such a method during study participation and for an additional 7 months after the end of treatment administration.
• Females of child-bearing potential must agree not to breastfeed starting at screening, throughout the study period and for 7 months after final study drug administration.

You may not qualify if:

• 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.
• Cardiovascular abnormalities including:
• 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.
• Uncontrolled/symptomatic or significant cardiovascular conditions within 6 months prior to enrollment, including but not limited to any of the following: Cardiac angioplasty or stenting, unstable angina pectoris, myocardial infarction, stroke/transient ischemic attack, coronary artery bypass graft surgery, symptomatic peripheral vascular disease, New York Heart Association (NYHA) class III-IV congestive heart failure, pericarditis, atrial fibrillation or other arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, or Torsades de Pointes).
• Symptomatic or radiographic leptomeningeal disease.
• Known other concurrent severe and/or uncontrolled medical condition that, in the investigator's judgment, would cause unacceptable safety risks, contraindicate patient participation in the clinical study or compromise compliance with the protocol (e.g., Celiac disease, Crohn's disease, gastric bypass, malabsorption, chronic pancreatitis, chronic active hepatitis, active untreated or uncontrolled fungal, bacterial or viral infections, etc.).
• With the exception of alopecia, any unresolved toxicities from prior therapy greater than National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE v5.0) Grade 1 at the time of starting study treatment and patients with chronic Grade 2 unresolved toxicities may be eligible following discussion with the Principal Investigator.
• Treatment with another investigational drug or other intervention within 5 half-lives of the investigational product whichever is longer.
• Prior treatment with another PRMT5 inhibitor.
• Known allergic reactions to components of BMS-986504: microcrystalline cellulose, croscarmellose sodium, colloidal silicon dioxide, magnesium stearate, polyvinyl alcohol, titanium dioxide, polyethylene glycol/macrogol, and talc.
• Use of strong inhibitors and strong inducers of CYP3A4/P-gp. Consider using alternative medications, per Investigator judgment.
• Concurrent use of medications known to prolong the QT interval (e.g., certain antiarrhythmics, antibiotics, antipsychotics, and antidepressants) unless discontinued for an appropriate washout period as determined by the investigator.
• Participants who have received live/attenuated vaccine within 30 days of anticipated first treatment. The use of inactivated seasonal influenza vaccines (e.g., Fluzone®) will be permitted on study without restriction.

Sponsors & Collaborators

• Nader Sanai: lead

Study Sites (1)

St. Joseph's Hospital and Medical Center

Phoenix, Arizona, 85013, United States

RECRUITING

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

Model Details: Single dose escalation arm with 3 dose cohorts

Study Record Dates

• First Submitted: February 25, 2025
• First Posted: March 19, 2025
• Study Start: April 28, 2025
• Primary Completion (Estimated): September 28, 2026
• Study Completion (Estimated): September 28, 2027
• Last Updated: June 19, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)