A Phase IIa, Open-label, Clinical Trial to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics, and Efficacy of BP1001 (a Liposomal Grb2 Antisense Oligonucleotide) in Combination With Venetoclax Plus Decitabine in Patients With AML Who Are Ineligible for Intensive Induction Therapy
The primary objectives of this study are to assess: (1) whether the combination of BP1001 plus venetoclax plus decitabine provides greater efficacy (Complete Remission \[CR\], Complete Remission with incomplete hematologic recovery \[CRi\], Complete Remission with partial hematologic recovery \[CRh\], than venetoclax plus decitabine alone (by historical comparison) in participants with untreated AML that cannot or elect not to be treated with more intensive chemotherapy; (2) whether BP1001-based treatment provides greater efficacy (CR, CRi, CRh) than intensive chemotherapy (by historical comparison) in participants with refractory/relapsed AML.
• At the time of Screening, participants must meet all of the following criteria to be considered eligible to participate in the study:
• Adults ≥18 years of age
• 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
• 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
• Histologically documented diagnosis (based on the 2008 World Health Organization \[WHO\] Classification) (Vardiman et al. 2009) of one of the following:
∙ Newly diagnosed untreated AML; or
‣ Untreated secondary AML, including AML that has progressed from MDS
‣ 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))
‣ Relapsed or Refractory AML
• 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
• Eligible for venetoclax and decitabine therapy, based on Investigator assessment
• 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.
• Adequate hepatic and renal functions as defined by:
∙ Aspartate transaminase (AST) and alanine transaminase (ALT) ≤2.5 times the upper limit of normal (ULN); and
‣ 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;
‣ 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
• Documented Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
⁃ Recovered from the effects of any prior surgery, radiotherapy, or antineoplastic treatment (with the exception of alopecia), based on Investigator assessment