Safety and Efficacy of BMS-986504 in Unresectable Malignant Peripheral Nerve Sheath Tumor

NCT07549022 | Not Yet Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: CASE3725
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

Brief Summary

People who have a cancer called MPNST, or Malignant Peripheral Nerve Sheath Tumor, may be eligible for this study. The purpose of this study is to see if a new medicine called BMS-986504 may work better than other available medicines for people with MPNST. Methylthioadenosine Phosphorylase (MTAP) loss is a gene mutation that some people have. MTAP loss seems to increase the chance that BMS-986504 can kill MPNST cancer cells. People who are missing MTAP from their tumor may be able to enroll in this study. Treating MPNST based on MTAP loss is considered experimental and is not approved by the US Food and Drug Administration (FDA) for determining whether BMS-98650 will be active against cancer. The purpose of this study is to evaluate the safety and effectiveness of BMS-986504 in participants with MPNST.

Conditions

Malignant Peripheral Nerve Sheath Tumors; MPNST

Keywords

BMS-986504

Outcome Measures

Primary Outcomes (1)

• Objective response rate (ORR)

  ORR is defined as the proportion of participants with a confirmed complete response (CR) or partial response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1). CR is defined as disappearance of all target lesions. PR is defined as at least a 30% decrease in the sum of diameters of target lesions.

  Up to 2 years

Secondary Outcomes (4)

• Progression free survival (PFS)

  Up to 2 years

• Overall survival (OS)

  Up to 2 years

• Incidence of adverse events (AEs)

  30 days post-treatment discontinuation (up to 2 years)

• Rate of treatment discontinuation

  Up to 2 years

Study Arms (1)

BMS-986504

EXPERIMENTAL

Participants will receive BMS-986504 on Days 1-28 of each cycle. Treatment will continue until disease progression, unacceptable toxicity, or withdrawal of consent.

Drug: BMS-986504

Interventions

BMS-986504 DRUG

Participants will receive 600 milligrams (mg) of BMS-986504 taken orally (by mouth) on Days 1-28 of each 28-day cycle. Treatment will continue until disease progression, unacceptable toxicity, or withdrawal of consent (up to 2 years). Participants who experience dose-limiting toxicity can be transitioned to 400 mg daily, then 200 mg daily of BMS-986504, or taken off the clinical trial. Nine participants will be enrolled in stage 1. If ≥ 1 participant demonstrates a complete or partial response in stage 1, the trial will proceed to stage 2, where an additional eight participants will be enrolled. If there are no responses or significant safety concerns arise, the trial will be halted.

BMS-986504

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female participants ≥ 12 years of age at the time of screening.
• Ability to understand and willingness to sign documentation of informed consent if ≥ 18 years of age or documentation of assent if 12-17 years of age.
• Pathohistological verification of MPNST.
• Measurable disease (size of primary tumor and metastatic lesions can be trended by CT or MRI scans).
• Unresectable (locally advanced or metastatic) disease.
• Confirmation of homozygous MTAP deletion by next generation sequencing
• Recovery from the adverse effects of prior therapy at the time of enrollment to baseline or ≤ Grade 1 (excluding alopecia, peripheral neuropathy, and parameters superseded by other eligibility criteria \[eg, hematology parameters\]). Note: Participants with prior endocrine adverse effects are permitted to enroll if they are stably maintained on appropriate replacement therapy and are asymptomatic.
• Recovery from the acute toxic effects (≤ grade 1 as defined by the National Cancer Institute Common Terminology Criteria for Adverse Events v5.0) of all prior chemotherapy prior to the entering study (exceptions: alopecia, anorexia, mass pain).
• Normal marrow function and recovery of blood cell counts from any myelosuppressive chemotherapy prior to entering study:
• Peripheral absolute neutrophil count (ANC) ≥ 1500/mcL (microliter).
• Hemoglobin ≥ 9 g/dL (packed red blood cell transfusion is not allowed up to 14 days prior to starting BMS-986504 treatment to meet eligibility).
• Platelet count ≥ 100,000/mcL (microliter) (platelet transfusion is not allowed up to 14 days prior to starting BMS-986504 treatment to meet eligibility).
• Adequate organ function, including:
• Liver function:
• Total bilirubin ≤ 1.5 times the upper limit of normal (ULN) for age, or ≤ 3 x ULN if associated with liver metastatic disease or Gilbert's disease).

You may not qualify if:

• Participants who have been treated previously with a PRMT5 inhibitor.
• Participants who are unable to swallow tablets.
• History of gastrointestinal disease, inflammatory bowel disease, major gastric surgery or other gastrointestinal conditions (eg, uncontrolled nausea, vomiting, malabsorption syndrome) likely to alter absorption of study treatment or result in inability to swallow oral medications.
• Participants with active drug use.
• Any botanical preparation (e.g., herbal supplements or traditional Chinese medicines) intended to treat the disease under study received within 4 weeks prior to randomization. The concurrent use of any botanical preparation is not permitted while on study.
• Ongoing need for a medication known as a strong inhibitor or strong inducer of CYP3A4 and/or P-gp or a PPI (proton pump inhibitor) that cannot be switched to an alternative treatment prior to randomization.

Sponsors & Collaborators

• Ankit Mangla, MD: lead

Study Sites (1)

University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center

Cleveland, Ohio, 44106, United States

Location

Related Publications (8)

• Miller, D.T., et al. (2019). Health supervision for children with neurofibromatosis type 1. Pediatrics, 143(5): e20190660. doi:10.1542/peds.2019-0660.

  BACKGROUND

• Kolb, S., et al. (2021). The Role of Radiation Therapy in the Treatment of Malignant Peripheral Nerve Sheath Tumors. Journal of Clinical Oncology. 39(25): 2762-2773. doi:10.1200/JCO.21.01232.

  BACKGROUND

• Montoya, P., et al. (2023). Methylthioadenosine Phosphorylase Deficiency in MPNST: Implications for Targeted Therapies. Neuro-Oncology. 25(S5): v238. doi:10.1093/neuonc/noad243.

  BACKGROUND

• Zhang, Y., et al. (2021). Loss of MTAP in cancer cells drives metabolic dependency on the arginine methylation pathway. Cancer Research. 81(13): 3538-3549. doi: 10.1158/0008-5472.CAN-21-0766.

  BACKGROUND

• Turner, J., et al. (2022). Targeting methylthioadenosine phosphorylase and arginine methylation for synthetic lethality in MTAP-deficient cancers. Nature Communications. 13(1): 1167. doi: 10.1038/s41467-022-29032-2.

  BACKGROUND

• Chang, L., et al. (2021). Protein arginine methyltransferase 5 inhibitors as therapeutic agents for cancer. Journal of Medicinal Chemistry.

  BACKGROUND

• Liu, W., et al. (2023). PRMT5 inhibition as a therapeutic strategy for MTAP-deficient cancers. Clinical Cancer Research. 29(3): 721-731. doi:10.1158/1078-0432.CCR-22-2479.

  BACKGROUND

• Walker, L., et al. (2023). Targeting PRMT5 in MTAP-deleted cancers: A synthetic lethal approach. Journal of Clinical Oncology. 41(4): 157-167. doi:10.1200/JCO.22.00399.

  BACKGROUND

MeSH Terms

Conditions

Neurofibrosarcoma

Condition Hierarchy (Ancestors)

Fibrosarcoma; Neoplasms, Fibrous Tissue; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma; Neurofibroma; Nerve Sheath Neoplasms; Neoplasms, Nerve Tissue; Peripheral Nervous System Neoplasms; Nervous System Neoplasms; Nervous System Diseases; Peripheral Nervous System Diseases; Neuromuscular Diseases

Study Officials

• Ankit Mangla, MD

  Case Comprehensive Cancer Center, University Hospitals

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ankit Mangla, MD

CONTACT

216-844-6031; ankit.mangla@uhhospitals.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: April 18, 2026
• First Posted: April 23, 2026
• Study Start: April 1, 2026
• Primary Completion (Estimated): April 1, 2028
• Study Completion (Estimated): July 1, 2028
• Last Updated: April 23, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)