BMS-986504 for Glioblastoma

Overseen By Phase 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 Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 3

9 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called BMS-986504, an experimental therapy, for people with recurrent glioblastoma, a type of brain cancer. Researchers aim to understand how the treatment moves through and affects the body, and whether it is safe and tolerable. The trial consists of two parts: the first part examines the treatment's effects on the tumor, and the second part continues treatment based on those initial results. The trial seeks participants who have previously been treated for glioblastoma, have a specific genetic marker (MTAP loss), and are scheduled for tumor-removal surgery. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

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.

Is there any evidence suggesting that BMS-986504 is likely to be safe for humans?

In other studies, patients have demonstrated that BMS-986504 can be administered safely, but researchers continue to test for side effects. Currently, no specific reports detail how people have reacted to it. As this is an early study, the main goal is to determine the drug's safety and the appropriate dosage. Scientists are closely monitoring participants' responses. Since this is a very early stage of testing, safety information is still being collected. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

BMS-986504 is unique because it targets glioblastoma with a fresh approach. Unlike traditional therapies such as surgery, radiation, and chemotherapy, BMS-986504 is designed for patients with a specific genetic alteration known as MTAP loss or deletion. Researchers are excited because BMS-986504 could offer a more personalized treatment option by directly targeting the genetic features of the tumor, potentially improving outcomes for patients who have limited options.

What evidence suggests that BMS-986504 might be an effective treatment for glioblastoma?

Research has shown that BMS-986504 works by blocking a protein called PRMT5. Cancer cells rely on PRMT5 for growth, so inhibiting it might slow or halt cancer progression. Early lab tests suggest that blocking PRMT5 could help treat tumors with a specific genetic issue known as MTAP loss. For this reason, BMS-986504 is being tested in this trial for individuals with recurrent glioblastoma, a type of brain cancer. Although information from human studies is limited, the treatment targets a known cancer growth pathway, which is promising. ^{1 2 4 6 7}

Who Is on the Research Team?

Nader Sanai, MD

Principal Investigator

Ivy Brain Tumor Center

Are You a Good Fit for This Trial?

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

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

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

Group I: Recurrent WHO Grade 4 Glioblastoma MTAP loss/deletion Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

Nader Sanai

Lead Sponsor

Trials

11

Recruited

440+

Published Research Related to This Trial

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06883747

Clinical Trial of BMS-986504 in Recurrent GBM Patients 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 ...

2. trialfinder.panfoundation.org trialfinder.panfoundation.org/en-US/trial/listing/585056

Clinical Trial of BMS-986504 in Recurrent GBM Patients 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 ...

3. withpower.com withpower.com/trial/early-phase-1-glioblastoma-2-2025-87c6a

BMS-986504 for Glioblastoma This Phase < 1 medical study run by Nader Sanai is evaluating whether BMS-986504 will have tolerable side effects & efficacy for patients with Glioblastoma.

4. researchgate.net researchgate.net/publication/396187340_P1227B_A_PHASE_01_STUDY_OF_PRMT5_INHIBITOR_BMS-986504_IN_RECURRENT_GLIOBLASTOMA_PARTICIPANTS_WITH_MTAP_DELETED_TUMORS

P12.27.B A PHASE 0/1 STUDY OF PRMT5 INHIBITOR ... This Phase 0/1 trial (NCT06883747) investigates the tumor pharmacokinetics (PK), pharmacodynamics (PD), and clinical activity of BMS-986504 in ...

5. trials.braintumor.org trials.braintumor.org/?page=5&trial_filter_form%5Bage%5D=56&trial_filter_form%5Bcontrol%5D=false&trial_filter_form%5Bdistance_radius%5D=20000&trial_filter_form%5Bkeyword%5D=+glioblastoma+recurrent+recurrent+recurrent+recurrent+glioblastoma&trial_filter_form%5Bzip_code%5D=&utf8=%C3%A2%C5%93%E2%80%9C

Filters - Clinical Trial Finder Clinical Trial of BMS-986504 in Recurrent GBM Patients. This is an open-label, multi-center, Phase 0/1 dose-escalation trial designed to enroll up to 9 total ...

6. anzctr.org.au anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=ACTRN12625001238460

ANZCTR - Registration To assess the safety of undertaking a peri-operative study with BMS-986504 in patients with recurrent MTAP-deleted glioblastoma (GBM). Query ...

7. ivybraintumorcenter.org ivybraintumorcenter.org/brain-tumor-clinical-trials/current-trials/bms-986504-in-recurrent-glioblastoma/

BMS-986504 in Recurrent Glioblastoma The main goal of this study is to evaluate how much BMS-986504 accumulates in the tumor tissue of participants. Patients who demonstrate adequate drug ...