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