Study on BP1001 Combined with Venetoclax and Decitabine for Acute Myeloid Leukemia (AML)

Inclusion Criteria

At the time of Screening, participants must meet all of the following criteria to be considered eligible to participate in the study:

1. Adults ≥18 years of age

2. Females must be of non-childbearing potential, surgically sterile, postmenopausal, or practice adequate methods of contraception during the study and for 30 days after the last dose of study drug or decitabine

3. Males must agree to use an adequate method of contraception during the study and for at least 30 days after the last dose of study drug or decitabine

4. Histologically documented diagnosis (based on the 2008 World Health Organization [WHO] Classification) (Vardiman et al. 2009) of one of the following:

   1. Newly diagnosed untreated AML; or
   2. Untreated secondary AML, including AML that has progressed from MDS
   3. In some cases of AML associated with specific genetic abnormalities, however, the diagnosis of AML may be made if the blast count is less than 20% (Dohner et al. 2017) - specifically AML with t(15;17), t(8;21), inv(16), or t(16;16))
   4. Relapsed or Refractory AML

5. Investigator considers previously untreated participant ineligible for (or unwilling to receive) intensive induction therapy based on medical reasons, disease characteristics such as genetics, type of AML (untreated or secondary), or participant characteristics such as age, performance status, co-morbidities, organ dysfunctions, or patient election of low-intensity treatment

6. Eligible for venetoclax and decitabine therapy, based on Investigator assessment

7. Participant's WBC count is 25 x 10^9/L or less at study initiation. The use of leukapheresis or hydroxyurea before treatment initiation to achieve this is permitted.

8. Adequate hepatic and renal functions as defined by:

   1. Aspartate transaminase (AST) and alanine transaminase (ALT) ≤2.5 times the upper limit of normal (ULN); and
   2. Usually total bilirubin ≤ 1.5 ULN. In specific cases the PI may request a waiver of this requirement with medical justification and agreement with the medical monitor and Bio-Path holdings. And;
   3. Estimated glomerular filtration rate (eGFR) of at least 40 ml/min. These estimations can be calculated using any of the following methods (Appendix E: Formulas):

   i. Chronic Kidney Disease Epidemiology Collaboration (CKD-Epi) equation

   • GFR = 141 × min (Scr /κ, 1)^α × max(Scr /κ, 1)^-1.209 × 0.993^Age × 1.018 [if female] × 1.159 [if black] ii. Cockcroft gault equation
   • Cockcroft Gault equation utilizing the TBW (Total body weight) to calculate an estimated creatinine clearance
   • CrCl = [(140 - age) x TBW] / (Scr x 72) x 0.85 [if female] iii. Modification of Diet in Renal Disease (MDRD) Study equation
   • GFR (mL/min/1.73 m^2) = 175 × (Scr)^-1.154 × (Age)^-0.203 × 0.74 [if female] x 1.212 [if African American (AA)] iv. Creatinine clearance estimated by 24-hr urine collection for creatinine clearance

9. Documented Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2

10. Recovered from the effects of any prior surgery, radiotherapy, or antineoplastic treatment (with the exception of alopecia), based on Investigator assessment

11. Willing and able to provide written informed consent 7.2. Exclusion Criteria

At the time of Screening, participants who meet any of the following criteria will be excluded from participating in the study:

1. Active non-hematologic or lymphoid malignancy other than AML treated with immuno- or chemotherapy within the previous 12 months except active non- melanoma, non-invasive skin cancer will be allowed.
2. Known, active leptomeningeal leukemia requiring intrathecal therapy. NOTE: Patients with a history of CNS disease may be allowed to participate based on at least 1 documented, negative spinal fluid assessment within 28 days prior to Screening
3. Isolated extramedullary leukemia without also meeting bone marrow criteria for acute leukemia (for AML usually = 20% blasts in BMA or BMB). Patients may have leukemia with lower blast counts (Dohner et al. 2010). Bio-Path Holdings and Investigator concurrence required.
4. Acute promyelocytic leukemia (APL) with t(15;17)(q22;q12) PML-RARA
5. Chronic myeloid leukemia (CML) in any phase
6. Receipt of any anti-cancer therapy within 14 days prior to C1D1, with the exception of hydroxyurea or anagrelide (within 24 hours), TKI (within 1day), a single dose of cytarabine (for proliferative disease)
7. Uncontrolled active, untreated, or progressive infection
8. Receipt of any investigational agent or study treatment within 30 days prior to C1D1
9. Females who are capable of becoming pregnant, test positive for pregnancy, or are breast-feeding during the Screening period, or intend to become pregnant or breast-feed during the course of the study or within 30 days after last dose of study drug
10. Serious intercurrent medical or psychiatric illness which, in the opinion of the Investigator, would interfere with the ability of the participant to complete the study
11. Known active or clinically significant hepatitis B infection (based on positive surface antigen [HBsAg]), hepatitis C infection (based on positive antibody [HCV Ab]), or human immunodeficiency virus (HIV-1 or HIV-2, based on positive antibody)
12. History of any hypersensitivity to venetoclax or decitabine, unless reaction is deemed irrelevant to the study by the Investigator and Medical Monitor
13. Presence of concurrent conditions that, in the opinion of the Investigator and/or Medical Monitor, may compromise the participant's ability to tolerate study treatment or interfere with any aspect of study conduct or interpretation of results. This includes but is not limited to, unstable or uncontrolled angina, New York Heart Association (NYHA) class III or IV congestive heart failure, uncontrolled and sustained hypertension, clinically significant cardiac dysrhythmia or clinically significant baseline ECG abnormality (e.g., QTcF >470 msec)
14. Within the past 6 months, has had any of the following: myocardial infarction, unstable angina pectoris, coronary/peripheral artery bypass graft, cerebrovascular accident or transient ischemic attack
15. Uncontrolled seizure disorder (i.e., seizures within the past 2 months)
16. Cannot receive live attenuated vaccine immunization prior to, during, or after treatment with venetoclax until B-cell recovery occurs
17. Unable or unwilling to communicate or cooperate with the Investigator or follow the protocol for any reason