- 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
- Patients must be at least 18 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.
- 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)
- Known active tuberculosis.
- Concurrent active inoperable locally advanced or metastatic malignancy (except for
malignancies which the 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.