Malignant Peripheral Nerve Sheath Tumors (MPNST)Phase 2NCT04872543
A Study of ASTX727 in People With Malignant Peripheral Nerve Sheath Tumors (MPNST)
A Phase 2 study testing ASTX727 in people with Malignant Peripheral Nerve Sheath Tumors (MPNST), run by Memorial Sloan Kettering Cancer Center at 7 sites in United States.
Trial summary
The purpose of this study is to see whether the study drug ASTX727 is an effective treatment for people who have MPNST with a PCR2 mutation. ASTX727 is a combination of two drugs (cedazuridine and decitabine) that have been designed to target cancer cells with a PCR2 mutation and to disrupt the cells' ability to… Read more about this study
- Who is it for?
- Ages 16 years and older
- Conditions the study is for
- Malignant Peripheral Nerve Sheath Tumors (MPNST)
- What is being tested?
- ASTX727
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 7 sitesUnited States
- Study dates
- 29 Apr 2021to Apr 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 16 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Patients must have pathologically confirmed PRC2 loss MPNSTs (e.g. IHC of loss H3K27me2 and/or H3K27me3 immunostaining, and/or inactivating mutations in EED, SUZ12, EZH2 by CLIA approved genetic assays), which are advanced, unresectable or metastatic and have progressed on at least one line of standard of care systemic therapy, or administration of cytotoxic chemotherapy is not considered in the best interest for the patient.
- Patients must be at least 16 years of age
- Patients must have Eastern Cooperative Oncology Group (ECOG) performance status of ≤2.
- Disease must be measurable by RECIST 1.1.
- Patients must be able to take oral medications.
- Patient or legally authorized representative can understand and comply with the protocol and must sign an informed consent document.
Show all 10Show fewer
- Adequate renal, hepatic and hematologic function as the following: serum creatinine ≤ 1.5 x upper limit of normal (ULN), total serum bilirubin ≤ 1.5 x ULN, serum AST (SGOT) ≤ 2.5 x ULN (or ≤ 5.0 x ULN if considered due to tumor (liver metastases)), serum ALT (SGPT) ≤ 2.5 x ULN (or ≤ 5.0 x ULN if considered due to tumor (liver metastases)), ANC ≥ 1500/µL, platelets ≥ 75,000/µL, and hemoglobin ≥ 9 g/dL(can be transfused to achieve this). Prothrombin time (PT), international normalized ratio (INR), and partial thromboplastin time > 1.5 x ULN. Patients on a stable maintenance regimen of anticoagulation therapy for at least 30 days prior to screening may have PT/INR measurements > 1.5 x ULN
- Patients of childbearing potential must have a negative serum pregnancy test at screening and at cycle 1 day 1 (-3 days) prior to the first dose of study therapy being administered. Female patients of childbearing potential must agree to use two reliable methods of contraception starting at signing the ICF, during and for 6 months following the last dose of study drug
- Women must agree not to breastfeed during treatment with study drug and for 2 weeks after the last dose.
- Sexually active males must agree to use a condom during intercourse and agree to not donate sperm while taking the drug and for 3 months after stopping treatment and should not father a child in this period. A condom is required to be used also by vasectomized men to prevent delivery of the drug via seminal fluid.
Who cannot join
- Patients have a severe and/or uncontrolled medical disease (e.g., uncontrolled diabetes, chronic renal disease, or active uncontrolled infection).
- Patients have known active brain metastasis or leptomeningeal disease.
- Active or chronic infection with hepatitis C virus (HCV) or hepatitis B virus (HBV) or known active or chronic infection with human immunodeficiency virus (HIV). Prior hepatitis infection that has been treated with highly effective therapy with no evidence of residual infection (including undetectable viral loads while on antiviral therapy) and with normal liver function (ALT, AST, total and direct bilirubin ≤ ULN) is allowed.
- Known active tuberculosis.
- Concurrent active inoperable locally advanced or metastatic malignancy (except for malignancies which the treating investigator determines are unlikely to interfere with treatment and safety analysis or are less of a treatment priority than their diagnosis of advanced MPNST).
- Patients have clinically significant cardiovascular disease, including any of the following: 1) History of acute coronary syndrome including myocardial infarction, unstable angina, CABG, coronary angioplasty or stenting < 6 months prior to screening; 2) symptomatic chronic heart failure (New York Heart Association Criteria, Class II-IV); 3) evidence of clinically significant cardiac arrhythmias and/or conduction abnormalities < 6 months prior to screening except atrial fibrillation (AF) and paroxysmal supraventricular tachycardia (PSVT).
Show all 13Show fewer
- A screening Fridericia corrected QT interval (QTcF) ≥ 450 ms (men) or ≥ 470 ms (women) (average of triplicates).
- Left ventricular ejection fraction (LVEF) <50% as determined by a multigated acquisition (MUGA) scan or echocardiogram.
- History of thromboembolic or cerebrovascular events ≤ 3 months prior to starting study treatment, including transient ischemic attacks, cerebrovascular accidents, deep vein thrombosis or pulmonary emboli.
- Impairment of gastrointestinal function or gastrointestinal disease (e.g., uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, ulcerative diseases, bowel resection with decreased intestinal absorption).
- Patients had a major surgery within 3 weeks prior to study entry or who have not recovered from side effects of such procedure.
- Patients with any significant history of non-compliance to medical regimens or with inability to grant reliable informed consent.
- Treatment with anti-cancer therapy within 14 days prior to the first dose of study drug therapy. For prior biological therapies, e.g., monoclonal antibodies with a half-life longer than 3 days, the interval must be at least 28 days prior to the first dose of study drug.
Trial locations and contacts
7 sites in 1 country. Contact the study team or a site near you to ask about taking part.
7 sites in 1 country
United States7 sites, 7 recruiting
- Recruiting
Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities)
Basking Ridge, New Jersey, 07920
Ping Chi, MD, PhD, 646-888-4166, zzPDL_MED_Sarcoma_Clinical_Trials@mskcc.org
- Recruiting
Memorial Sloan Kettering Commack (Limited Protocol Activities)
Commack, New York, 11725
Ping Chi, MD, PhD, 646-888-4166, zzPDL_MED_Sarcoma_Clinical_Trials@mskcc.org
- Recruiting
Memorial Sloan Kettering Westchester (Limited Protocol Activities)
Harrison, New York, 10604
Ping Chi, MD, PhD, 646-888-4166, zzPDL_MED_Sarcoma_Clinical_Trials@mskcc.org
- Recruiting
Memorial Sloan Kettering Monmouth (Limited Protocol Activities)
Middletown, New Jersey, 07748
Ping Chi, MD, PhD, 646-888-4166, zzPDL_MED_Sarcoma_Clinical_Trials@mskcc.org
- Recruiting
Memorial Sloan Kettering Bergen (Limited Protocol Activities)
Montvale, New Jersey, 07645
Ping Chi, MD, PhD, 646-888-4166, zzPDL_MED_Sarcoma_Clinical_Trials@mskcc.org
- Recruiting
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
Ping Chi, MD, PhD, 646-888-4166, zzPDL_MED_Sarcoma_Clinical_Trials@mskcc.org
Ciara Kelly, MBBCH BAO, 646-888-4312
- Recruiting
Memorial Sloan Kettering Nassau (Limited Protocol Activities)
Uniondale, New York, 11553
Ping Chi, MD, PhD, 646-888-4166, zzPDL_MED_Sarcoma_Clinical_Trials@mskcc.org
About this study
Official title: A Phase II Study of ASTX727 in Patients With PRC2 Loss Malignant Peripheral Nerve Sheath Tumor (MPNST)
The purpose of this study is to see whether the study drug ASTX727 is an effective treatment for people who have MPNST with a PCR2 mutation.
ASTX727 is a combination of two drugs (cedazuridine and decitabine) that have been designed to target cancer cells with a PCR2 mutation and to disrupt the cells' ability to survive and grow. The study researchers think that the study drug allows decitabine to work better than decitabine given alone.
- Being tested
- ASTX727
- Keywords
- ASTX727, Cedazuridine, Decitabine, PRC2 mutation, 21-048
- Medical subject headings
- Neurofibrosarcoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ASTX727Drug
ASTX727 will be self-administered orally by the patient on a once daily basis, days 1 through 5 of each 21-day cycle. Cycle 1 day 1 (C1D1) is defined as the first day that ASTX727 is administered.
| Study group | Role | What they receive |
|---|---|---|
| ASTX727 (cedazuridine and decitabine) | Experimental | Patients who meet the eligibility criteria will be treated with oral ASTX727 (INQOVI) on days 1-5 of each 21-day cycle with Pegfilgrastim support on day 7. A delay in the start of subsequent cycles due to holidays, weather, or other circumstances will be permitted up to 7 days and not considered a protocol deviation. Drug dosing will be interrupted for any Grade 4 adverse events or clinically significant laboratory abnormalities. For Grade 3 or 4 AE, if the AE returns to Grade 1 or baseline, the patient may be re-escalated. Receives: Drug: ASTX727 |
What is being measured
The primary outcome is the main question the study is designed to answer.
the best clinical benefit rate (CBR)
(complete response [CR] + partial response [PR] + stable disease [SD]) by RECIST1.1
Measured: at the end of 16 weeks
Secondary outcomes (1)
objective response rate (ORR)
by RECIST1.1
Measured: 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 May 2021
- Study start29 Apr 2021
- Primary completionApr 2027 (estimated)
- Study completionApr 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Malignant Peripheral Nerve Sheath Tumors (MPNST)Studies of the same condition, open and under way.
- More trials run by Memorial Sloan Kettering Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- This is a phase II trial to evaluate the efficacy of ASTX727 in patients with PRC2-loss MPNST.
- Masking
- None (open label)
- Enrolment
- 25 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Memorial Sloan Kettering Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- Taiho Pharmaceuticals, Inc.
- Responsible party
- Sponsor
- Investigators
- Ping Chi, MD, PhD, Principal investigator, Memorial Sloan Kettering Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04872543
- Sponsor's protocol ID
- 21-048
- Other IDs
- 1R01FD007544-01, Philanthropy
- Status last verified
- Feb 2026
- First submitted
- 30 Apr 2021
- Last updated
- 5 Feb 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.
Study at a glance
From the registry record, last updated by the sponsor on 5 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of ASTX727 in Patients With PRC2 Loss Malignant Peripheral Nerve Sheath Tumor (MPNST)
- ClinicalTrials.gov ID
- NCT04872543
- Acronym / sponsor ID
- 21-048
- Keywords
- ASTX727, Cedazuridine, Decitabine, PRC2 mutation, 21-048
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 25 participants (estimated)
- Lead sponsor
- Memorial Sloan Kettering Cancer CenterUniversity, hospital or other
- Collaborators
- Taiho Pharmaceuticals, Inc.
- Study start
- 29 Apr 2021 (actual)
- Primary completion
- Apr 2027 (estimated)
- Study completion
- Apr 2027 (estimated)
- First posted
- 4 May 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to see whether the study drug ASTX727 is an effective treatment for people who have MPNST with a PCR2 mutation.
ASTX727 is a combination of two drugs (cedazuridine and decitabine) that have been designed to target cancer cells with a PCR2 mutation and to disrupt the cells' ability to survive and grow. The study researchers think that the study drug allows decitabine to work better than decitabine given alone.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- This is a phase II trial to evaluate the efficacy of ASTX727 in patients with PRC2-loss MPNST.
| Arm | Type | Receives |
|---|---|---|
| ASTX727 (cedazuridine and decitabine) | Experimental | Drug: ASTX727Patients who meet the eligibility criteria will be treated with oral ASTX727 (INQOVI) on days 1-5 of each 21-day cycle with Pegfilgrastim support on day 7. A delay in the start of subsequent cycles due to holidays, weather, or other circumstances will be permitted up to 7 days and not considered a protocol deviation. Drug dosing will be interrupted for any Grade 4 adverse events or clinically significant laboratory abnormalities. For Grade 3 or 4 AE, if the AE returns to Grade 1 or baseline, the patient may be re-escalated. |
Who may qualify
- Ages
- 16 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (10 listed)
- Patients must have pathologically confirmed PRC2 loss MPNSTs (e.g. IHC of loss H3K27me2 and/or H3K27me3 immunostaining, and/or inactivating mutations in EED, SUZ12, EZH2 by CLIA approved genetic assays), which are advanced, unresectable or metastatic and have progressed on at least one line of standard of care systemic therapy, or administration of cytotoxic chemotherapy is not considered in the best interest for the patient.
- Patients must be at least 16 years of age
- Patients must have Eastern Cooperative Oncology Group (ECOG) performance status of ≤2.
- Disease must be measurable by RECIST 1.1.
- Patients must be able to take oral medications.
Key exclusion criteria (13 listed)
- Patients have a severe and/or uncontrolled medical disease (e.g., uncontrolled diabetes, chronic renal disease, or active uncontrolled infection).
- Patients have known active brain metastasis or leptomeningeal disease.
- Active or chronic infection with hepatitis C virus (HCV) or hepatitis B virus (HBV) or known active or chronic infection with human immunodeficiency virus (HIV). Prior hepatitis infection that has been treated with highly effective therapy with no evidence of residual infection (including undetectable viral loads while on antiviral therapy) and with normal liver function (ALT, AST, total and direct bilirubin ≤ ULN) is allowed.
- Known active tuberculosis.
- Concurrent active inoperable locally advanced or metastatic malignancy (except for malignancies which the treating investigator determines are unlikely to interfere with treatment and safety analysis or are less of a treatment priority than their diagnosis of advanced MPNST).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ASTX727ASTX727 will be self-administered orally by the patient on a once daily basis, days 1 through 5 of each 21-day cycle. Cycle 1 day 1 (C1D1) is defined as the first day that ASTX727 is administered. | Drug | ASTX727 (cedazuridine and decitabine) |
Primary outcome
the best clinical benefit rate (CBR)
Time frame: at the end of 16 weeks
(complete response [CR] + partial response [PR] + stable disease [SD]) by RECIST1.1
1 secondary outcome
objective response rate (ORR)
Time frame: 8 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Feb 2026.
- Memorial Sloan Kettering Cancer CenterLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.
Related trials for Malignant Peripheral Nerve Sheath Tumors (MPNST)
RecruitingObservational study
Surveillance for Malignant Transformation of Neurofibromatosis Type 1 (NF1) Related Peripheral Nerve Sheath Tumors (PNST)
Neurofibromatosis 1, Nerve Sheath Neoplasms
Active, not recruitingPhase 2
Testing Whether Cancers With Specific Mutations Respond Better to Glutaminase Inhibitor, Telaglenastat Hydrochloride, Anti-Cancer Treatment, BeGIN Study
Advanced Malignant Solid Neoplasm, Metastatic Malignant Solid Neoplasm
RecruitingPhase 1
Metarrestin (ML-246) in Subjects With Metastatic Solid Tumors
Advanced Solid Tumors, Metastatic Pancreatic Cancer
RecruitingPhase 1
A First-in-Human Phase I Trial With Antibody Drug Conjugate ADCT-701 in Neuroendocrine Tumors, Carcinomas and Malignant Peripheral Nerve Sheath Tumors
Neuroendocrine Carcinomas, Neuroendocrine Tumors
Not yet recruitingPhase 2
Combination of Avutometinib and Defactinib for Treatment of Relapsed, Refractory, Metastatic, or Unresectable Malignant Peripheral Nerve Sheath Tumor
MPNST (Malignant Peripheral Nerve Sheath Tumor)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Ping Chi, MD, PhD principal investigator
Memorial Sloan Kettering Cancer Center
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing ASTX727 in people with Malignant Peripheral Nerve Sheath Tumors (MPNST), run by Memorial Sloan Kettering Cancer Center at 7 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 5 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Ping Chi, MD, PhD (646-888-4166, zzPDL_MED_Sarcoma_Clinical_Trials@mskcc.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
the best clinical benefit rate (CBR) (time frame: at the end of 16 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Feb 2026.