To evaluate the safety, pharmacokinetics (PK), and efficacy of ASTX660 when given alone and
in combination with ASTX727 in participants with relapsed/refractory (R/R) acute myeloid
leukemia (AML). The duration of the study is expected to be approximately 30 months.
This is a three-part dose escalation and dose expansion Phase 1 study of ASTX660 alone and in
combination with ASTX727 in adults with R/R AML.
Part 1 is an open-label, single arm, dose escalation with ASTX660 in combination with ASTX727
at the standard fixed dose combination (FDC).
Part 2 is an open-label, randomized, dose escalation intended to evaluate ASTX660 as a
monotherapy and ASTX660 in combination with ASTX727 FDC.
Part 3 is an exploratory single arm dose expansion to further expand the number of
participants treated with ASTX660 in combination with ASTX727 FDC.
1. Have a projected life expectancy of at least 12 weeks, as assessed by the
2. Have histological confirmation of AML by World Health Organization (WHO) 2016 criteria
and are either:
1. refractory to intensive induction chemotherapy OR
2. relapsed after intensive induction chemotherapy or stem cell transplant OR
3. relapsed after or refractory to treatment with molecularly targeted and/or
low-intensity chemotherapeutic regimens.
3. Have an Eastern Cooperative Oncology Group (ECOG) Performance status of 0 to 2.
4. Have adequate renal function as demonstrated by measured or calculated creatinine
clearance ≥60 mL/min.
5. Have adequate liver function as demonstrated by:
1. Aspartate aminotransferase (AST) ≤2.5 × upper limit of normal (ULN)
2. Alanine aminotransferase (ALT) ≤2.5 × ULN
3. Bilirubin ≤1.5 × ULN - unless considered due to leukemic organ involvement.
6. Women of child-bearing potential (according to recommendations of the Clinical Trial
Facilitation Group [CTFG]) must not be pregnant or breastfeeding and must have a
negative pregnancy test at screening.
1. Poor medical risk in the investigator's opinion because of systemic diseases in
addition to the cancer under study, for example, uncontrolled infections.
2. Known clinically active central nervous system (CNS) leukemia.
3. BCR-ABL-positive leukemia (chronic myelogenous leukemia in blast crisis).
4. Diagnosis of acute promyelocytic leukemia (M3 AML or APML).
5. Second malignancy currently requiring active therapy, except breast or prostate cancer
stable on or responding to endocrine therapy.
6. Graft Versus Host Disease (GVHD), or any GVHD requiring treatment with
immunosuppression. Any GVHD treatment (including calcineurin inhibitors) must be
discontinued at least 28 days prior to Day 1 of study treatment.
7. Presence of persistent toxicities of Grade >1 from prior treatment including
chemotherapy, targeted therapy, immunotherapy, experimental agents, radiation, and
surgery (except for alopecia).
8. Hypersensitivity to decitabine, ASTX727, ASTX660, or any of their excipients.
9. Liver cirrhosis, or chronic liver disease Child-Pugh Class B or C.
10. Life-threatening illness, significant organ system dysfunction, or other condition
that, in the investigator's opinion, could compromise participant safety, or the
integrity of study outcomes, or interfere with the absorption or metabolism of ASTX660
11. History of, or at risk for, cardiac disease.
12. Known human immunodeficiency virus (HIV), active hepatitis B virus (HBV), or active
hepatitis C virus (HCV) infection (participants with laboratory evidence of no active
replication will be permitted).
13. Known significant mental illness or other conditions, such as active alcohol or other
substance abuse that, in the opinion of the investigator, predispose the participant
to high risk of noncompliance with the protocol treatment or assessments.
14. Treated with any investigational therapy within 2 weeks of the first dose of study
15. Prior treatment with hypomethylating agent (ie, decitabine or azacitidine) for more
than 2 cycles.
16. Inability to swallow oral medication or inability or unwillingness to comply with the
administration requirements related to ASTX660-02 (Note: G-tube administration is not