ClinicalTrials.gg
RecruitingNCT07549022Updated Aug 11, 2026

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

A Phase 1/2 interventional study of BMS-986504 in Malignant Peripheral Nerve Sheath Tumors and MPNST, sponsored by Ankit Mangla, MD. Recruiting at 1 site in United States. Open to participants aged 12 Years and older. Per ClinicalTrials.gov, last updated 2026-08-11.

Sponsored by Ankit Mangla, MD · Phase 1/2, Interventional, and Treatment

Phase
Phase 1/2
Study type
Interventional
Enrollment
17
Allocation
Not applicable
Ages
12 Years and older
Sex
All
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Study 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.

Read the detailed description

Malignant Peripheral Nerve Sheath Tumors (MPNSTs) are fast-growing, aggressive cancers that develop in soft tissues. They are the main cause of serious illness and death in people with neurofibromatosis type 1 (NF1), a condition that increases the risk of cancer. MPNSTs are rare, affecting about 1 in 100,000 people. In the United States, about 800 to 1,000 new cases are diagnosed each year. The 5-year survival rate is about 50%. However, this drops to about 20% when the cancer has spread or cannot be removed with surgery. Chemotherapy is often less effective, especially when the tumor cannot be removed by surgery, with response rates under 20%. There is a strong need to develop new and more targeted therapies for this type of cancer.

When some benign (non-cancerous) nerve tumors, called neurofibromas, turn into MPNST, it is often caused by the loss of a group of genes called CDKN2A on chromosome 9. These genes normally help prevent tumors from forming. When a part of chromosome 9 called 9p21 is deleted, it can also cause the loss of a nearby gene called MTAP. MTAP is missing in about 25-50% of people with MPNST. MTAP plays an important role in the methionine salvage pathway and serves a critical role in methylation reactions. When MTAP is lost, cells have problems with purine metabolism and become more dependent on another pathway, the arginine methylation pathways. This pathway is important for processes like DNA repair and control of the cell cycle. An enzyme called protein arginine methyltransferase 5 (PRMT5) helps carry out arginine methylation by adding small chemical groups (methyl groups) to proteins. When both copies of the MTAP gene are lost (called homozygous deletion), cells rely even more on PRMT5 to survive. At the same time, a substance called methylthioadenosine builds up and partly blocks PRMT5 activity. Because of this, completely blocking PRMT5 can cause MTAP-deficient cancer cells to die, a concept known as "synthetic lethality." For people with MPNST who have homozygous MTAP deletion confirmed by next-generation sequencing (NGS), drugs that block PRMT5 may help shrink tumors. A drug called BMS-986504 is a first-in-class PRMT5 inhibitor designed to specifically target MTAP-deficient tumor cells by binding to the PRMT5-MTA complex.

BMS-986504 was recently studied in a Phase 1 trial and showed evidence of anti-tumor activity. People with tumors that could not be removed with surgery with a homozygous MTAP deletion and whose disease had gotten worse since their last treatment were given varying doses of BMS-986504. Three of the 6 people enrolled had disease progression. The remaining 3 participants had partial responses, meaning that there was a >30% improvement from their baseline per RECIST v1.1 criteria. Each of these 3 participants had different doses of the study drug, which suggests a dose-independent response.

Since the current treatments for MPNST that cannot be removed through surgery are poor, it is important to identify new treatment strategies that may improve how long someone lives with this type of cancer and their health outcomes. This study aims to assess the safety and efficacy of BMS-986504 in people with MPNST that cannot be removed with surgery and with homozygous MTAP deletion.

02

Conditions studied

  • Malignant Peripheral Nerve Sheath Tumors
  • MPNST

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Keywords

  • BMS-986504
03

In context

Neurofibrosarcoma

98 studies on the registry are indexed under Neurofibrosarcoma; 23 are open to participants now.

This study's planned enrollment of 17 is below the median of 46 across 84 interventional studies indexed under Neurofibrosarcoma.

Browse Neurofibrosarcoma studies →

Lead sponsor

This is the only study on the registry with Ankit Mangla, MD as lead sponsor.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
12 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

  • Male or female participants ≥ 12 years of age at the time of screening.
  • Ability to understand and willingness to sign documentation of if ≥ 18 years of age or documentation of assent if 12-17 years of age.
  • Pathohistological verification of MPNST.

    • (size of primary tumor and 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 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 (ANC) ≥ 1500/mcL (microliter).
    • ≥ 9 g/dL (packed red blood cell transfusion is not allowed up to 14 days prior to starting BMS-986504 treatment to meet eligibility).
    • 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 ≤ 1.5 times the (ULN) for age, or ≤ 3 x ULN if associated with liver metastatic disease or Gilbert's disease).
        • (alanine transaminase) and AST (aspartate aminotransferase) \< 3 x ULN for age, or \< 5 x ULN if associated with liver metastatic disease.
        • Serum albumin ≥ 2.0 g/dL.
        • PT () and/or INR (International Normalized Ratio) ≤ 1.5 x ULN, or within therapeutic range if receiving anticoagulant therapy.
      • Renal function:

        • Creatinine \< 1.5 times institutional ULN for age.
  • Performance status at time of screening:

    • (Eastern Cooperative Oncology Group) performance status 0-1 for participants ≥ 18 years old.
    • Lansky performance status (ages 12-15) or performance status (ages 16-17) ≥ 50.
  • Individuals of (IOCBP) must practice effective during the trial.

Exclusion criteria

Exclusion Criteria:

  • 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 and/or P-gp or a PPI (proton pump inhibitor) that cannot be switched to an alternative treatment prior to randomization.
Terms in these criteria, in plain language(16)

Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.

Informed consent

Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.

You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.

Measurable disease

The amount of disease can be tracked with a defined measurement, so the study can see whether it shrinks or grows. It might be a tumour measured on a scan or, in some blood cancers such as myeloma, a marker measured in blood or urine.

The criteria or the study team say which measurement counts — having no tumour visible on a scan does not by itself rule you out.

Metastases

Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.

CTCAE grade

The US National Cancer Institute’s scale of how severe an adverse event is — any unwanted medical event during a study, such as a symptom, an illness or an abnormal test result, whether or not a treatment caused it. Whether it did is judged separately.

1
Mild.
2
Moderate.
3
Severe.
4
Life-threatening.
5
Death due to the event.

“Side effects of earlier treatment resolved to grade 1 or less” means they have settled to mild or gone.

Absolute neutrophil count (ANC)

The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.

It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.

Hemoglobin (Hb)

The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).

Platelets

Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.

Bilirubin

A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.

Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.

ULN (upper limit of normal)

The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.

“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.

ALT and AST (liver enzymes)

Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.

Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.

INR, PT and aPTT (clotting tests)

Blood tests of how long blood takes to clot. The INR is the prothrombin time (PT) put on a common scale; about 1 is usual for someone not taking a blood thinner.

Criteria often make an exception for people on a blood thinner such as warfarin, whose INR is raised on purpose.

ECOG performance status

A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.

0
Fully active, no restrictions.
1
Limited in strenuous activity, but walking and able to do light work, such as housework or office work.
2
Walking and able to look after yourself, but unable to work; up and about more than half of waking hours.
3
Able to look after yourself only in part; in bed or a chair more than half of waking hours.
4
Unable to look after yourself at all; in bed or a chair all day.

Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.

Karnofsky performance status (KPS)

A 0–100 scale of how well someone can carry out everyday activities. 100 is no complaints and no signs of illness; 70 is able to look after yourself but not to work or keep up normal activity; 50 is needing considerable help and frequent medical care.

Studies often ask for 60 or 70 and above. Your doctor gives the score.

Childbearing potential

Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).

Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.

Contraception

Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.

Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.

CYP3A (CYP3A4) inhibitors and inducers

CYP3A is a group of enzymes, mainly CYP3A4, in the liver and gut that break down many medicines. Some medicines, supplements and foods (grapefruit, St John’s wort) slow them down or speed them up, which changes how much of a study drug stays in the body.

Studies list them so they can be avoided or switched; bring a list of everything you take, including supplements.

05

Study design

Phase
Phase 1 / Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
17 participants (estimated)

Study arms

  • Experimental
    BMS-986504

    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

  • 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.

06

What researchers measure

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.

    Time frame: Up to 2 years

Secondary outcomes

  1. Progression free survival (PFS)

    Progression-Free Survival (PFS) is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first.

    Time frame: Up to 2 years

  2. Overall survival (OS)

    OS is defined as the time from treatment initiation to death from any cause.

    Time frame: Up to 2 years

  3. Incidence of adverse events (AEs)

    AEs will be defined and graded per the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v5.0).

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

  4. Rate of treatment discontinuation

    Proportion of participants discontinuing treatment due to toxicity will be calculated.

    Time frame: Up to 2 years

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Study locations

1 of 1 sites recruiting
08

References and documents

Publications

  • Miller DT, Freedenberg D, Schorry E, Ullrich NJ, Viskochil D, Korf BR; COUNCIL ON GENETICS; AMERICAN COLLEGE OF MEDICAL GENETICS AND GENOMICS. Health Supervision for Children With Neurofibromatosis Type 1. Pediatrics. 2019 May;143(5):e20190660. doi: 10.1542/peds.2019-0660. PubMed 31010905 ↗
  • 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.
  • Montoya, P., et al. (2023). Methylthioadenosine Phosphorylase Deficiency in MPNST: Implications for Targeted Therapies. Neuro-Oncology. 25(S5): v238. doi:10.1093/neuonc/noad243.
  • 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.
  • 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.
  • Chang, L., et al. (2021). Protein arginine methyltransferase 5 inhibitors as therapeutic agents for cancer. Journal of Medicinal Chemistry.
  • 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.
  • 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.

Individual participant data

Plan to share: No

09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Aug 11, 2026, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT07549022
Lead sponsor
Ankit Mangla, MD
Responsible party
Ankit Mangla, MD (Principal Investigator, Case Comprehensive Cancer Center) — Sponsor-investigator
First posted
Apr 23, 2026
Start date
Aug 2026 (estimated)
Primary completion
Apr 2028 (estimated)
Completion
Jul 2028 (estimated)
Last update
Aug 11, 2026

Study contacts

Ankit Mangla, MD
Contact
ankit.mangla@uhhospitals.org
216-844-6031
Ankit Mangla, MD
principal investigator · Case Comprehensive Cancer Center, University Hospitals

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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