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Treatment for Malignant Peripheral Nerve Sheath Tumors with ASTX727

A Phase II Study of ASTX727 in Patients With PRC2 Loss Malignant Peripheral Nerve Sheath Tumor (MPNST)

Phase 2 Interventional Memorial Sloan Kettering Cancer Center · NCT04872543

This study is testing if a new combination treatment called ASTX727 can help people with advanced malignant peripheral nerve sheath tumors that have a specific mutation feel better compared to using decitabine alone.

Quick facts

PhasePhase 2
Study typeInterventional
Enrollment25 (estimated)
Ages16 Years and up
SexAll
SponsorMemorial Sloan Kettering Cancer Center Academic / other
Drugs / interventionschemotherapy
Locations7 sites (Basking Ridge, New Jersey and 6 other locations)
Trial IDNCT04872543 on ClinicalTrials.gov

What this trial studies

This study evaluates the effectiveness of ASTX727, a combination of cedazuridine and decitabine, in treating patients with malignant peripheral nerve sheath tumors (MPNST) that have a PRC2 mutation. The aim is to determine if this combination therapy can improve outcomes compared to decitabine alone. Participants must have advanced, unresectable, or metastatic MPNST that has progressed after at least one line of standard treatment. The study will assess the drug's ability to disrupt cancer cell survival and growth.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with pathologically confirmed PRC2 loss MPNSTs that are advanced and have not responded to previous therapies.

Not a fit: Patients with MPNST that do not have a PRC2 mutation or those who are not eligible for oral medications may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new effective option for patients with MPNST and PRC2 mutations.

How similar studies have performed: Other studies have shown promise with similar combination therapies targeting specific mutations, suggesting potential for success in this approach.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria:

* 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.
* 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.

Exclusion Criteria:

* 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).
* 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.

Where this trial is running

Basking Ridge, New Jersey and 6 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Malignant Peripheral Nerve Sheath TumorsASTX727CedazuridineDecitabinePRC2 mutation21-048
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.