APG-2575 Study of Safety, Tolerability ,PK/PD in Patients With Hematologic Malignancies

APG-2575 will be administered orally, once daily for consecutive 4 weeks as one cycles.
Initially, the start dose is 20mg. Single patient cohorts will be evaluated, the dose of
APG-2575 will be increased in subsequent cohorts, to 50 mg, 100 mg, 200 mg, 400 mg, 600mg and
800mg accordingly. If there is any one of the following event is observed, a DLT, two drug
related Grade 2 toxicities or one drug related ≥ Grade 3 toxicity, or laboratory or clinical
TLS, or suspected hypersensitivity reaction occur in Cycle 1, or dose level of 400 mg is
reached, the dose escalation will convert to the standard 3+3 design, If ≥ 2/6 patients
develop DLT at any dose level dose escalation will cease and the dose level immediately below
will be expanded to 6 patients. If ≤ 1/6 patients develop a DLT at the highest dose reached
this will be declared the MTD. After the MTD is defined, a maximum of 20 patients will be
treated at that dose level.

Inclusion Criteria:

1. Age ≥18 years old.

2. Histologically confirmed diagnosis of either one of the B-cell hematologic
malignancies including multiple myeloma, chronic lymphocytic leukemia,
lymphoplasmacytic lymphoma, and non-Hodgkin's lymphoma such as mantle cell lymphoma,
diffuse large B cell lymphoma, Waldenstrom macroglobulinemia (WM) and acute myeloid
leukemia

3. Patient must have relapsed or refractory to, intolerant to, or are considered
ineligible for therapies known to provide clinical benefit. In addition,

a. AML Patients will be eligible if they have failed standard induction regimen, are
not considered candidate for further chemotherapy or stem cell transplantation or have
primary refractory AML.

4. Life expectancy ≥ 3 months.

5. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS): 0 -1 in dose
escalation ; 0-2 in dose expansion.

6. QTc interval ≤450ms in males, and ≤470ms in females.

7. Adequate bone marrow function independent of growth factor:

8. Absolute neutrophil count (ANC) ≥1.0 X 109/L.

9. Hemoglobin ≥ 8.0 g/dL.

10. Platelets count ≥ 30 X 109/L (entry platelet count must be independent of transfusion
within 7 days of first dose).

11. Adequate renal and liver function as indicated by:

Exclusion Criteria:

Patients who meet any of the following exclusion criteria are not to be enrolled in this
study:

1. Prior history of allogeneic cell transplant.

2. Subjects have been diagnosed with Burkitt's lymphoma, Burkitt-like lymphoma, or
lymphoblastic lymphoma/leukemia.

3. Received chemotherapy within 14 days (42 days for nitrosoureas or mitomycin C) prior
to entering the study.

4. Received biologic (< 28 days), small molecule targeted therapies (< 5 half-life) or
other anti-cancer therapy within 21 days of study entry.

5. Radiation within 14 days of study entry, thoracic radiation within 28 days of study
entry.

6. Has gastrointestinal conditions that could affect the absorption of APG-2575 in the
opinion of the Investigator.

7. Has known active central nervous system (CNS) involvement.

8. Continuance of toxicities due to prior radiotherapy or chemotherapy agents that do not
recover to ≤ Grade 1 except alopecia or neuropathy.

9. Concurrent treatment with an investigational agent, 14 days for small molecular agents
and/or 28 days for biologics treatment prior to the first dose of therapy.

10. Failure to recover adequately, as judged by the investigator, from prior surgical
procedures. Patients with active wound healing, patients who have had major surgery
within 28 days from study entry, and patients who have had minor surgery within 14
days of study entry.

11. Unstable angina, myocardial infarction, or a coronary revascularization procedure
within 180 days of study entry.

12. Active rheumatoid arthritis (RA), active inflammatory bowel disease, chronic
infections, or any other disease or condition associated with chronic inflammation.

13. Active infection requiring systemic antibiotic/ antifungal medication, known
clinically active hepatitis B or C infection, or on antiretroviral therapy for HIV
disease.