RECRUITING

Clinical Trial of BMS-986504 in Recurrent GBM Patients

Conditions

Glioblastoma WHO Grade IV MTAP loss MTAP deletion MTAP del

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

A Phase 0/1 Study of BMS-986504, a MTA Cooperative PRMT5 Inhibitor in Recurrent Glioblastoma Participants With MTAP Deleted Tumors Scheduled for Resection to Evaluate Central Nervous System (CNS) Penetration With PK-Triggered Expansion Cohort

Quick Facts

Study Start:2025-04-14

Study Completion:2027-06-14

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT06883747

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion 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.	* 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.

Inclusion Criteria

Exclusion 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.

* 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.

Contacts and Locations

Study Contact

Phase 0 Navigator

CONTACT

602-406-8605

research@ivybraintumorcenter.org

Principal Investigator

Nader Sanai, MD

PRINCIPAL_INVESTIGATOR

Ivy Brain Tumor Center

Study Locations (Sites)

St. Joseph's Hospital and Medical Center

Phoenix, Arizona, 85013

United States

Collaborators and Investigators

Sponsor: Nader Sanai

Nader Sanai, MD, PRINCIPAL_INVESTIGATOR, Ivy Brain Tumor Center

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2025-04-14

Study Completion Date2027-06-14

Study Record Updates

Study Start Date2025-04-14

Study Completion Date2027-06-14

Terms related to this study

Keywords Provided by Researchers

MTAP loss
MTAP deletion
MTAP del

Additional Relevant MeSH Terms

Glioblastoma WHO Grade IV