A Phase I/II Dose Escalation and Expansion Study of BST-236 Plus Venetoclax in Patients With Unfit Newly Diagnosed AML

Inclusion Criteria

• Adult ≥18 years of age
• Diagnosis of AML (de-novo AML or AML secondary to MDS or secondary to exposure to potentially leukemogenic therapies or agents)
• Not eligible for standard induction chemotherapy
• Peripheral white blood cell (WBC) count of <25,000/μL
• Creatinine clearance ≥45 mL/min
• AST and/or aALT ≤2.5 X ULN)
• Total bilirubin ≤1.5 x ULN
• ECOG PS of:
• 0 to 2 for patients ≥75 years of age
• 0 to 3 for patients <75 years of age
• Women of reproductive potential must have a negative serum pregnancy test within 48 hours of Study Day 1

Exclusion Criteria

• Patient has acute promyelocytic leukemia
• Any previous treatment for AML
• Patient has a known history of myeloproliferative neoplasm (MPN)
• Patient has known active central nervous system (CNS) involvement with AML
• Use of an investigational drug within 5 half-lives (or 30 days in case the half-life is unknown) prior to Study Day 1
• Previous BM/stem cell transplantation (SCT)
• Previous treatment for MDS with cytarabine, hypomethylating agents, or venetoclax
• For Part 1 only - use of known strong or moderate CYP3A inducers within 7 days prior to Study Day 1
• Patient has consumed grapefruit, grapefruit products, Seville oranges (including marmalade containing Seville oranges), or starfruit within 3 days prior to Study Day 1
• Patient has a malabsorption syndrome or other condition that precludes enteral route of drug administration
• Uncontrolled systemic fungal, bacterial, or viral infection (defined as ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics or other treatment)
• Any medical or surgical condition, presence of clinical safety laboratory abnormalities, or psychiatric illness that may preclude safe and complete study participation based on the Investigator's judgment.
• Diagnosis of malignant disease other than AML within the previous 12 months
• Diagnosis of myeloid sarcoma as a sole manifestation of AML
• Unstable angina, significant cardiac arrhythmia, or New York Heart Association (NYHA) Class IV CHF
• History of allergic reactions attributed to compounds of similar chemical composition as BST-236 and/or cytarabine and/or venetoclax.
• Surgical procedure, excluding central venous catheter placement or other minor procedures (e.g. skin biopsy) in the 14 days prior to enrollment