This is a multicenter, open-label Phase 1 study of orally administered CB-5339 in
participants with R/R AML or participants with R/R intermediate- to high-risk MDS. The study
will include two parts:1) a Dose Escalation phase in participants with R/R AML, or R/R
intermediate- to high-risk MDS and 2) a Dose Expansion phase in participants with R/R AML for
whom there is no standard of care therapy available that is likely to lead to disease
remission. Additional cohorts for participants with R/R intermediate- to high-risk MDS
following hypomethylating agents or other AML cohorts may be added at a later time.
1. Male or female and ≥ 18 years of age at the time of signing the consent form
2. One of the following advanced hematologic malignancies including:
- Relapsed or refractory AML as defined by 2016 WHO criteria and are not candidates
for curative therapies such as allogeneic hematopoietic cell transplant or for
whom there is no standard of care therapy available that is likely to lead to
disease remission according the investigator
- MDS high-very high risk by the revised international scoring system for
evaluating prognosis in myelodysplastic syndromes that is recurrent or refractory
or the participant is intolerant to established therapy known to provide clinical
benefit for their condition (e.g., relapsed following treatment with
hypomethylating agent or lack of response after > 4 cycles), according to
treating physician. Potential participants who meet the criteria for intermediate
risk may be considered with approval by the medical monitor if the participant
has severe cytopenia(s) and/or elevated bone marrow blast counts.
3. Adequate organ function defined as:
- Serum creatinine ≤1.5 mg/dL or an estimated glomerular filtration rate of ≥60
mL/min as calculated by the Cockcroft-Gault glomerular filtration rate equation
- Total bilirubin ≤ 1.5 × the upper limit of normal (ULN) unless considered due to
Gilbert's disease or leukemic disease
- Aspartate aminotransferase (AST) ≤3 × the ULN; alanine aminotransferase (ALT) ≤3
× the ULN. Levels of AST and/or ALT ≤5 × the ULN may be acceptable for
participants with known leukemic involvement of the liver after discussion with
the study medical monitor
4. Eastern Cooperative Oncology Group (ECOG) performance status ≤2.
5. Contraceptive use by men or women should be consistent with local regulations
regarding the methods of contraception for those participating in clinical studies. If
of childbearing potential, agree to use an effective barrier method of birth control
(i.e., latex condom, diaphragm, cervical cap, etc.) to avoid pregnancy during the
study and 90 days after the last dose of CB-5339. Female participants of childbearing
potential need a negative serum or urine pregnancy test within 7 days of study
enrollment. Non-childbearing is defined as ≥ 1 year postmenopausal or surgically
6. Capable of giving signed informed consent as described in Appendix 1 which includes
compliance with the requirements and restrictions listed in the informed consent form
(ICF) and in this protocol
1. Acute promyelocytic leukemia with t(15;17)(q22;q12); or abnormal promyelocytic
leukemia/retinoic acid receptor alpha (PML-RARA).
2. Participants with clinical symptoms suggestive of active central nervous system (CNS)
leukemia or known CNS leukemia. Evaluation of cerebrospinal fluid is only required if
there is a clinical suspicion of CNS involvement by leukemia during screening.
3. Participants with immediately life-threatening, severe complications of leukemia such
as uncontrolled bleeding, pneumonia with hypoxia or shock, and/or disseminated
4. Concomitant malignancy, requiring active treatment, except for basal-cell or squamous
cell carcinoma of the skin, carcinoma-in-situ of the uterine cervix, or localized
• Adjuvant therapy for breast cancer or prostate cancer is allowed.
5. Active, uncontrolled, systemic infection or severe localized infection during
screening or prior to Cycle 1 Day 1 (C1D1; unless considered due to tumor by the
• Note, participants receiving prophylactic anti-infectives are allowed on study.
6. Known human immunodeficiency virus (HIV) infection with CD4+ T cell counts <350
cells/μL, initiation of antiretroviral therapy within 4 weeks before C1D1, or acquired
immunodeficiency syndrome (AIDS)-related infection within 12 months before C1D1.
7. Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection with viral load above the
limit of quantification
8. Major cardiac abnormalities as defined but not limited to the following: uncontrolled
angina or unstable life-threatening arrhythmias, history of myocardial infarction
within 12 weeks prior to Baseline, Class 3 or higher New York Heart Association (NYHA)
congestive heart failure, or left ventricular ejection fraction (LVEF) <45% as
measured by echocardiogram (ECHO) within 28 days of C1D1
9. Persistent (3 consecutive ECGs performed ≥5 minutes apart) prolongation of the
corrected QT interval by Fredericia's method (QTcF) to > 480 msec
10. Gastrointestinal conditions that may interfere with the absorption of
orally-administered drugs including but not limited to short gut syndrome,
gastroparesis, inflammatory bowel disease, or acute pancreatitis.
11. Any other severe, acute, or chronic medical or psychiatric condition, or laboratory
abnormality that may increase the risk associated with study participation or CB-5339
administration, may interfere with the informed consent process and/or with compliance
with the requirements of the study, may interfere with the interpretation of the study
results and, in the Investigator's opinion, or would make the participant
inappropriate for entry into this study
12. A condition that is expected to require concomitant use of any medication listed as
prohibited while on study.
13. Known hypersensitivity to any components of CB-5339.
14. Use of chemotherapy (except hydroxyurea), radiation or monoclonal antibodies within 14
days or 5 half-lives for small molecule inhibitors prior to first dose of CB-5339
15. Participants who have undergone a hematopoietic cell transplant (HCT) within 100 days
of the first dose of CB-5339, or participants on immunosuppressive therapy post-HCT at
the time of screening, use of calcineurin inhibitors within 4 weeks prior to first
dose of CB-5339, or with clinically significant graft-versus-host disease (GVHD).
• Note: The use of topical steroids or <10mg oral prednisone for ongoing skin GVHD is
16. Major surgery within 4 weeks prior to first dose of CB-5339. Participant must have
recovered from surgery and be without current complications of infection or dehiscence
17. Enrollment in other clinical trials unless approved by Medical Monitor