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9 Participants Needed

BMS-986504 for Glioblastoma

Overseen ByPhase 0 Navigator

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Nader Sanai

Must not be taking: Antidepressants, Antipsychotics, Antibiotics

Disqualifiers: Infections, Cardiovascular issues, others

No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

Trial Summary

Will I have to stop taking my current medications?

The trial requires a 21-day period without chemotherapy before starting, and you may need to stop using certain medications that affect the heart's rhythm or interact with the trial drug. It's best to discuss your current medications with the trial team to see if any changes are needed.

What makes the drug BMS-986504 unique for treating glioblastoma?

BMS-986504 is unique because it may target glioma cancer stem-like cells (GCSCs), which are responsible for tumor growth and resistance to standard treatments. This approach could potentially improve treatment outcomes by addressing the root cause of tumor maintenance and resistance.¹ ² ³ ⁴ ⁵

What is the purpose of this trial?

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.

Research Team

Nader Sanai, MD

Principal Investigator

Ivy Brain Tumor Center

Eligibility Criteria

This trial is for up to 9 people with recurrent glioblastoma (rGBM) who have a specific genetic change called MTAP loss/deletion in their tumor. They must be scheduled for surgery and the genetic change is confirmed by advanced DNA testing.

Inclusion Criteria

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

Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests and other procedures

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

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Exclusion Criteria

Inability to undergo MRI brain with intravenous (IV) contrast

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.)

Treatment with another investigational drug or other intervention within 5 half-lives of the investigational product whichever is longer

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Timeline

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

Phase 0 Dose Escalation

Participants receive BMS-986504 in three dose escalation cohorts over 6 days prior to surgical resection.

6 days

Daily visits for dosing and monitoring

Phase 1 Expansion

Participants with positive PK response continue treatment with BMS-986504 in 21-day cycles.

21-day cycles

Follow-up

Participants are monitored for safety and effectiveness after treatment, with survival data collection every 3 months for up to 12 months.

12 months

Every 3 months

Treatment Details

Interventions

BMS-986504

Trial Overview The study tests BMS-986504, a new drug, in two phases: an initial phase to understand how the body processes it and its safety, followed by a longer treatment phase if early results are positive.

Participant Groups

1Treatment groups

Experimental Treatment

Group I: Recurrent WHO Grade 4 Glioblastoma MTAP loss/deletionExperimental Treatment1 Intervention

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Who Is Running the Clinical Trial?

Nader Sanai

Lead Sponsor

Trials

Recruited

440+

Findings from Research

Despite aggressive treatment options for glioblastoma, including surgery and chemotherapy, the median survival remains low at 14-16 months, highlighting the need for new therapeutic strategies.

Recent data suggest that the Optune™ device, which delivers alternating electrical field therapy, may improve survival in newly diagnosed glioblastoma patients, indicating a promising new approach alongside traditional treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

What next for newly diagnosed glioblastoma?Domingo-Musibay, E., Galanis, E.[2022]

In a phase I study involving 12 patients with newly diagnosed glioblastoma, dimethyl fumarate (DMF) was safely combined with standard treatments of radiotherapy and temozolomide, with no dose-limiting toxicities observed.

The recommended phase 2 dose (RP2D) for DMF was established at 240 mg three times daily, and the median progression-free survival was 8.7 months, with a median overall survival of 13.8 months, indicating potential efficacy in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I trial of dimethyl fumarate, temozolomide, and radiation therapy in glioblastoma.Shafer, D., Tombes, MB., Shrader, E., et al.[2022]