Inclusion Criteria:  Subject must be ≥ 18 years of age.  Subject must have a confirmed diagnosis of an advanced hematologic malignancy, specified as follows:  R/R AML (subjects who relapse after transplantation; subjects in second or later relapse; subjects who are refractory to initial induction or reinduction treatment; subjects who relapse within 1 year of initial treatment). Subjects with AML must have previously failed all prior therapies known to be active for treatment of their diagnosed hematologic disease. R/R MDS. Subjects with MDS must have previously failed treatment with at least 4 cycles of a hypomethylating agent, known to be active for treatment of their diagnosed hematologic disease. Subject must be able to understand and be willing to sign an informed consent. Subject must be willing and able to comply with scheduled study visits and treatment plans. Subject must be willing to undergo all study procedures (fresh bone marrow biopsy and/or aspirate at baseline within 28 days of first dose plus bone marrow evaluations every 4 weeks for the first 24 weeks, then every 8 weeks for the next 48 weeks of treatment, as clinically indicated thereafter, and 1 EOT bone marrow evaluation (unless contraindicated due to medical risk; other exceptions to this are at the discretion of the Sponsor's Medical Monitor), peripheral blood and tissue sampling, and urine sampling during the study. Subject must have an ECOG PS of ≤ 2. Subject must have a life expectancy of ≥ 3 months.  Subject must have adequate hepatic function as evidenced by:  Serum total bilirubin ≤ 1.5 × upper limit of normal (ULN), unless considered due to leukemic involvement following approval by the study Sponsor Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) ≤ 3.0 × ULN, unless considered due to leukemic involvement following approval by the study Sponsor Prothrombin time (PT) ≤ 1.5 × ULN or international normalized ratio (INR) ≤ 1.4 Activated partial thromboplastin time (aPTT) ≤ ULN No known portal vein thrombosis  Subject must have adequate renal function as evidenced by:  • Creatinine clearance > 60 mL/min based on the Cockcroft-Gault glomerular filtration rate (GFR) estimation  Subject must have an adequate platelet level, defined as:  • Platelets > 50 × 109/L (transfusions to achieve this level are allowed.) Subjects with a baseline platelet count of ≤ 50 × 109/L due to underlying malignancy are eligible with Medical Monitor approval.  Subject must have adequate cardiovascular, respiratory, and immune system function as evidenced by the below criteria and in the opinion of the Investigator:  • LVEF of ≥ 40% by ECHO  Subjects must agree to discontinue intake of beverages, herbal supplements, or food known to inhibit or induce cytochrome P450 (CYP) 3A such as grapefruit juice, St John's wort, echinacea, and goldenseal from 72 hours before admission until 72 hours following final dose of study drug.  Timing requirements with respect to prior therapy and surgery are as follows:  2 weeks and/or at least 5 half-lives, whichever is shorter, must have elapsed since administration of the last dose of any prior systemic anticancer therapy. Hydroxyurea is allowed prior to enrollment and after the start of FHD-286 for the control of peripheral leukemic blasts in subjects with leukocytosis (eg, white blood cell [WBC] counts > 30 × 109/L) with approval of the Medical Monitor. (Patients must either be intolerant to and/or have experienced disease progression on their prior therapy in the opinion of the treating physician.) 4 weeks must have elapsed since the last dose of post-transplant calcineurin inhibitors. 4 weeks must have elapsed since the last major surgery, 2 weeks for minor surgery (eg, port placement). 2 weeks must have elapsed since the last radiotherapy. Exceptions may be made in the case of palliative radiotherapy at the discretion of the Medical Monitor. Toxicity related to prior therapy must have returned to ≤ Grade 2 by CTCAE at least 14 days prior to study start or be deemed irreversible by the Investigator. Exceptions include alopecia, neuropathy, appropriately controlled endocrine toxicities, and other toxicities similar to these with discussion with the Medical Monitor.  Female subjects must be:  postmenopausal, defined as at least 12 months post cessation of menses (without an alternative medical cause), or permanently sterile following documented hysterectomy, bilateral salpingectomy, bilateral oophorectomy, or tubal ligation or having a male partner with vasectomy as affirmed by the subject, or nonpregnant, nonlactating, and if sexually active having agreed to use a highly effective method of contraception (ie, hormonal contraceptives associated with inhibition of ovulation or intrauterine device [IUD], or intrauterine hormone-releasing system [IUS], or sexual abstinence) from Screening Visit until 90 days after the final dose of the study drug.  Note: The potential risk to female fertility posed by FHD-286 is unknown; it is recommended that subjects discuss options for fertility preservation with their doctor prior to study start.  Male subjects must have documented vasectomy or if sexually active must agree to use a highly effective method of contraception with their partners of childbearing potential (ie, hormonal contraceptives associated with the inhibition of ovulation or IUD, or IUS, or sexual abstinence) from Screening until 90 days after the final dose of the study drug. Male subjects must agree to refrain from donating sperm during this time period.  Note: The potential risk to male fertility posed by FHD-286 is unknown; it is recommended that subjects discuss options for fertility preservation with their doctor prior to study start.  Exclusion Criteria:  Subject is unable to provide informed consent and/or to follow protocol requirements. Subject has undergone HSCT within 60 days of the first dose of FHD-286, or subject is on immunosuppressive therapy post-HSCT at the time of screening, or subject has clinically significant graft-versus-host disease (GVHD). The use of a stable dose of oral steroids post-HSCT is permitted with Medical Monitor approval. Subject has clinical symptoms suggesting active central nervous system (CNS) leukemia or known CNS leukemia. Evaluation of the cerebrospinal fluid is only required if there is a clinical suspicion of CNS involvement by leukemia during screening. Subject has an immediately life-threatening, severe complications of leukemia, such as uncontrolled bleeding, pneumonia with hypoxia or shock, and/or disseminated intravascular coagulation. Subject has other malignancy which may interfere with the diagnosis and/or treatment of advanced hematologic malignancies. Subject has active hepatitis B virus (HBV) or hepatitis C virus (HCV) infections; subjects with a sustained viral response to HCV treatment or immunity to prior HBV infection will be permitted. Subject has known positive human immunodeficiency virus (HIV)antibody results, or acquired immunodeficiency syndrome (AIDS)-related illness; subjects with CD4+ T-cell counts ≥ 350 cells/μL will be permitted as will subjects who have not had an AIDS-related illness within the past 12 months. Subject has an active severe infection that requires anti-infective therapy or has an unexplained temperature of > 38.5°C during screening visits or on their first day of study drug administration (at the discretion of the Investigator, subjects with tumor fever may be enrolled). Subject has an uncontrolled intercurrent illness. Subjects with corrected QT interval (QTc) using Fridericia's formula (QTcF) > 470 msecs or other factors that increase the risk of QTc prolongation or arrhythmic events (eg, heart failure, hypokalemia, family history of long QT interval syndrome) including heart failure that meets New York Heart Association (NYHA) class III and IV definitions are excluded. Subject has any other medical or psychological condition, deemed by the Investigator to be likely to interfere with a subject's ability to sign informed consent, cooperate, or participate in the study. Subject has known allergies or hypersensitivities to components of the FHD-286 formulation. Subject is unable to tolerate the administration of oral medication or has GI dysfunction that could interfere with absorption of FHD-286 (eg, ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, partial bowel resections). Subject is receiving any other investigational agents. Subject has participated in any other clinical trials within 2 weeks or at least 5 half-lives of a prior investigational drug at the start of study treatment. Exceptions include participation in any observational or nontherapeutic clinical trials. Subject is on medications that are strong CYP3A inhibitors, are strong CYP3A inducers, or are sensitive CYP3A substrates with narrow TIs. Exceptions may be made for therapy in the case of life-threatening infections, for example a triazole anti-fungal agent to reduce the risk of invasive fungal infections, at the discretion of the Medical Monitor. Subject is on medications with narrow TIs that are sensitive P-gp or breast cancer BCRP substrates and are administered orally, such as digoxin or on medications that are strong inhibitors of P-gp or BCRP. Subject on medications that are acid-reducing agents (ARA) such as histamine H2-receptor antagonists (H2 blockers), and proton pump inhibitors (PPIs). The last dose of PPIs must be administered 7 days prior to administration of study drug. Antacids are acceptable when administered in a staggered dosing manner with FHD-286. Subject is receiving systemic steroid therapy or any other systemic immunosuppressive medication. The use of a stable dose of oral steroids post-HSCT is permitted with Medical Monitor approval. Local steroid therapies (inhaled or topical steroids) are acceptable. Appropriate steroid replacement to manage endocrine toxicities resulting from prior anticancer systemic therapy is permitted. Subject has undergone any prior treatment with a BRG1/BRM inhibitor. Subject is pregnant or breastfeeding or is planning to become pregnant within 1 year of study start. Subject is a woman or man of childbearing capabilities who is unwilling to use effective contraception.