A First in Human Study of AUR 103 Calcium to Evaluate Safety, Pharmacokinetics and Pharmacodynamics

Exclusion Criteria

• •Previous Treatments:
• •4. Eastern Cooperative Oncology Group (ECOG) (Appendix D) Performance status of 0 or 1 (Patients with disease related ECOG 2 are allowed, in addition to ECOG 0 and 1).
• •5. Acceptable bone marrow as described below:
• •Part 1 ANC greater than1500/μL (without WBC growth factor support). Platelet count greater than100,000/μL without transfusion support. Hemoglobin greater than 9 g/dL (Transfusion is allowed to achieve this Hb). Part 2A and 2B WBC Less than 20,000/μL (Hydroxyurea can be given to reduce WBC count to Less than 20,000/μl). Platelet count greater than 50,000/μL without transfusion support. Hemoglobin greater than 9 g/dL (Transfusion is allowed to achieve this Hb). Part 3A and 3BANCgreater than 1000 / μL. Platelet count greater than 50,000/μL without transfusion support. Hemoglobin greater than9 g/dL (Transfusion is allowed to achieve this Hb).
• •6. Acceptable organ function as described below:
• •Total Bilirubin less than 1.5 x ULN; (Patients with known Gilbert's syndrome are allowed with a Total Bilirubin Less than 2.5 x ULN). AST (SGOT) Less Than 3 x ULN (Less than 5 × ULN if known liver metastases). ALT (SGPT) Less than 3 x ULN (less than 5 × ULN if known liver metastases). Creatinine clearance (CrCl) greater than 60 mL/min (either measured or estimated by the Cockcroft-Gault formula). (Cockcroft-Gault formula for estimated creatinine clearance \[eCrCl\]: eCrCl = \[140 - Age\] × Weight \[kg\] × \[0.85 if Female\] / \[72 × serum creatinine (mg/dL)\]). Albumin greater than 3.0 g/dL
• •7. Ability to swallow and retain oral medications.
• •8. Negative serum pregnancy test in women of childbearing potential (WOCBP).
• •9. Women of childbearing potential and men who partner with such a woman of childbearing potential must agree to use one or more of highly effective method(s) for contraception for the duration of the study, i.e.,through 28-day follow up visit, after discontinuation of study drug(s).
• •10. Evidence of measurable disease per RECIST, v1.1 for solid tumors (Eisenhauer et al. 2009, Appendix E) and per Lugano Criteria for Lymphoma (Cheson et al. 2014, Appendix J). Measurable disease for solid tumors is defined as at least one lesion that can be accurately measured in at least 1 dimension with a minimum size of 10 mm for non-nodal lesions or 15 mm in short axis for nodal lesions. For malignant lymphomas, measurable disease is defined as a lesion that can be accurately measured with a minimum size of 10 mm in both dimensions or 15 mm in greatest transverse diameter. AML/MDS patients are per WHO 2016 criterion.
• •1. Systemic anti-cancer therapy, such as chemotherapy, or biological therapy, immunomodulatory drug therapy, received within the past 28 days or 5 half-lives, whichever is shorter, from the Cycle 1 Day 1 of the study. Concomitant use of prednisone or medroxyprogesterone is allowed. In Part 1, Patients with CRPC (castrate resistant prostate cancer) should continue to receive ongoing medical castration with LHRH analogues, and such patients are allowed.
• •2. Acute promyelocytic leukemia (AML M3 subtype).
• •3. Patients eligible for intensive chemotherapy for AML (such as the 3 + 7 regimen).
• •4. CML in blast crisis (i.e., patients with known bcr-abl positive disease).
• •5. Presence of an acute or chronic toxicity resulting from prior anti cancer treatment, with the exception of alopecia or nail changes, that has not resolved to Grade Less than 1, as determined by NCI CTCAE v 5.0 (Appendix G).
• •6. Definitive Radiotherapy within the last 21 days of Cycle 1 Day 1 (limited field palliative radiation is allowed and no restrictions during the screening period or during the trial).
• •7. Use of any investigational agent within 28 days or 5 half-lives (whichever is shorter) prior to Cycle 1 Day 1.
• •8. Known symptomatic or untreated or recently treated (Less than 6 months of screening) central nervous system (CNS) metastases or CNS lymphoma or CNS leukemia. Patients with previously treated (greater than 6 months of screening) CNS metastases or CNS lymphoma or CNS leukemia and are now stable and asymptomatic, from CNS perspective, are allowed.
• •9. Major surgery Less than 28 days from Cycle 1 Day 1 (major surgery is defined as a procedure requiring general anesthesia).
• •10. Known to be human immunodeficiency virus (HIV) positive or have an acquired immunodeficiency syndrome-related illness.
• •11. Known active or chronic hepatitis B or hepatitis C infection.
• •12. Uncontrolled congestive heart failure (New York Heart Association \[NYHA\] Class 2-4), angina, myocardial infarction, cerebrovascular accident, coronary/peripheral artery bypass graft surgery, or transient ischemic attack, or pulmonary embolism within 3 months prior to Cycle 1 Day 1
• •13. Ongoing cardiac dysrhythmias requiring treatment of any gradeor treatment of cardiac dysrhythmias in past 3 months, before Cycle 1 Day 1.
• •14. The QTcF (corrected QT interval Fridericia method) value in the screening ECG greater than 450 ms in males and greater than 460 ms in females.
• •15. Previous allogeneic stem cell or bone marrow transplantation
• •16. NHL subtypes of Burkitt Lymphoma, Lymphoblastic Lymphoma, AIDS related lymphoma, Primary CNS Lymphoma, Waldenstrom Macroglobulinemia, Castleman Disease, Post Transplant Lymphoproliferative Disorder and anaplastic large B cell lymphoma.