Recruiting
Early Phase 1

BMS-986504

Sponsor:

Nader Sanai

Code:

NCT06883747

Conditions

Glioblastoma WHO Grade IV

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

BMS-986504

Study Details

Brief summary:

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.

Conditions

Glioblastoma WHO Grade IV

Study ID

NCT06883747

Start date

Apr 28, 2025

Status verified date

Mar, 2026

Completion date

Sep 28, 2027

Anticipated

Primary completion date

Sep 28, 2026

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

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 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.
  • For males of reproductive potential: use of condoms or other methods to ensure effective contraception with partner and avoid sperm donation for the duration of the study and for an additional 4 months after the end of treatment administration.
  • Agreement to adhere to Lifestyle Considerations throughout study duration.
  • Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests and other procedures.
  • Participant 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 informed consent for the protocol must be obtained prior to any screening procedures. If consent cannot be expressed in writing, it must be formally documented and witnessed, ideally via an independent trusted witness.

Exclusion Criteria:

  • 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.

Study Design

Enrollment

12 participants

Anticipated

Intervention Model

Single group

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Recurrent WHO Grade 4 Glioblastoma MTAP loss/deletion

Interventions

BMS-986504

MTA cooperative PRMT5 inhibitor

Primary outcome measure

  • BMS-986504 Concentration in Tumor Tissue [ Time Frame: intraoperative ]
  • Number of Treatment-Emergent Adverse Events [ Time Frame: From date of enrollment until 30 days after last dose, assessed over 15 months ]
  • Number of Treatment-Related Adverse Events [ Time Frame: From date of first dose of study drug until 30 days after last dose, assessed over 15 months ]
  • Number of Serious Adverse Events [ Time Frame: From date of enrollment until 30 days after last dose, assessed over 15 months ]
  • Number of Clinical Laboratory Abnormalities [ Time Frame: From date of enrollment until 30 days after last dose, assessed over 15 months ]
  • Number of Drug-Related Toxicities [ Time Frame: From date of first dose of study drug until 30 days after last dose, assessed over 15 months ]

Central Contacts and Locations

Central contacts

Phase 0 Navigator

602-406-8605research@ivybraintumorcenter.org

Locations

St. Joseph's Hospital and Medical Center

Recruiting

Phoenix, Arizona, United States, 85013

Contacts

Phase 0 Navigator

602-406-8605research@ivybraintumorcenter.org

Principal Investigator:

Nader Sanai, MD

More Information

Sponsor

Nader Sanai

Last update posted

Jun 25, 2026

Last verified

Mar, 2026

Keywords

  • MTAP loss
  • MTAP deletion
  • MTAP del

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by Nader Sanai on 2026-06-25.