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
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.
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.
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 →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.
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.
Pathohistological verification of MPNST.
Normal marrow function and recovery of blood cell counts from any myelosuppressive chemotherapy prior to entering study:
Adequate organ function, including:
Liver function:
Renal function:
Performance status at time of screening:
Exclusion Criteria:
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.
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.
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.
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
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.
“Side effects of earlier treatment resolved to grade 1 or less” means they have settled to mild or gone.
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.
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).
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.
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.
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.
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.
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.
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.
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.
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.
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.
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 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.
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.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Metastases
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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.
“Side effects of earlier treatment resolved to grade 1 or less” means they have settled to mild or gone.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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).
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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.
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.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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
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.
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
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
Overall survival (OS)
OS is defined as the time from treatment initiation to death from any cause.
Time frame: Up to 2 years
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)
Rate of treatment discontinuation
Proportion of participants discontinuing treatment due to toxicity will be calculated.
Time frame: Up to 2 years
Plan to share: No
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Studies of the drug tested here: Navlimetostat