Study of APG2575 Single Agent and Combination Therapy in Patients With Relapsed/Refractory CLL/SLL

Inclusion Criteria:

Subjects who meet each of the following inclusion criteria are eligible to participate in this study:

1. Age ≥18 years old.

2. Diagnosis as relapsed/refractory chronic lymphocytic leukemia/ small lymphocyticlymphoma according to the IWCLL NCI-WG guidelines revised in 2008.

3. Through radiological assessment, subjects with a lymph node length ≥ 10 cm requireprior approval from the sponsor before enrollment.

4. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS): 0 -1.

5. QTcF interval ≤450ms in males, and ≤470ms in females.

6. Adequate bone marrow function independent of growth factor and transfusion.

7. Adequate renal and liver function.

8. Willingness by males, female patients of child bearing potential, and their partnersto use contraception by effective methods throughout the treatment period and for atleast three months following the last dose of study drug.

9. Pregnancy test results of serum samples obtained within 14 days before the firststudy drug administration in fertile female subjects were negative; If the serumpregnancy test results obtained are> 7 days from the first administration, urinesample obtained before the first study dose of study drug must be negative.

10. Male subjects must avoid sperm donation throughout the treatment period and for atleast three months following the last dose of study drug.

11. Ability to understand and willingness to sign a written informed consent formapproved by EC committee (the consent form must be signed by the patient prior toany screening or study-specific procedures).

12. Willingness and ability to comply with study procedures and follow-up examination.

Exclusion Criteria:

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

1. Prior history of allogeneic hematopoietic stem cell transplantation, adoptive cellimmunotherapy within 24 months or autologous hematopoietic stem cell transplantationwithin 12 months.

2. Monoclonal antibody therapy against CLL was adopted within 4 weeks prior to thefirst dose of the study drug.

3. Receive any of the following treatments within 14 days or 5x half-life before thefirst dose of study drug, or clinically significant adverse reactions / toxicitiesdue to previous treatments have not recovered to ≤ Grade 1: Anti-tumor therapiesinclude chemotherapy, radiotherapy, anti-tumor steroid treatment, anti-tumor Chinesemedicine treatment; investigational treatment, including targeted small moleculedrugs.

4. Use the following drugs within 14 days before the first dose of study drug:moderately potent CYP3A inhibitors such as fluconazole, ketoconazole andclarithromycin; moderately potent CYP3A inducers such as rifampin, carbamazepine,phenytoin And St. John's wort.

5. Failure to recover adequately, at the discretion of the investigator, from priorsurgical procedures. Patients who have had major surgery within 28 days from studyentry, and patients who have had minor surgery within 14 days of study entry.

6. Received Bcl-2 inhibitor treatment.

7. Invasive NHL transformation or central nervous system (CNS) involvement. hasoccurred.

8. Cardiovascular disease of grade ≥2 (New York Heart Association Class).

9. A significant history of renal, neurological, psychiatric, pulmonary, endocrine,metabolic, immune, cardiovascular or liver disease. The investigator believes thatparticipating in this study will have an adverse effect on him / her. For subjectsrequiring intervention for any of the above diseases in the past 6 months, theinvestigator and the sponsor must discuss.

10. Warfarin or other anticoagulants is required.

11. Known to be allergic to study drug ingredients or their analogues.

12. Pregnancy or lactation, or pregnancy is expected during the study period or within 3months after the last administration of treatment.

13. Within 3 years before entering the study, the subject had a history of activemalignant tumors other than CLL / SLL, except that:

• Fully treated cervical carcinoma in situ;

• Completely resected basal cell carcinoma of the skin or localized squamous cellcarcinoma of the skin;

• confinement and resection of previously cured malignancies (or othertreatment).

14. Has malabsorption syndrome or other conditions that are not suitable for enteraladministration.

15. Uncontrolled other clinically significant symptoms, including but not limited to:uncontrolled systemic infections (viruses, bacteria, or fungi), including but notlimited to known hepatitis B virus (HBV) surface antigens and DNApositive(HBV-DNA≥2000copies/mL or ≥500IU/mL); Hepatitis C virus (HCV) antibodypositive or RNA positive; human immunodeficiency virus (HIV) antibody positive;Febrile neutropenia occured within 1 week before administration.

16. Primary active autoimmune diseases and connective tissue diseases, such as activeand uncontrolled primary autoimmune hemocytopenia, including autoimmune hemolyticanemia (AIHA) and primary immune thrombocytopenia (ITP).

17. Any other condition or circumstance that would, at the discretion of theinvestigator, make the patient unsuitable for participation in the study.