Study of APG-2575 in Patients With Relapsed/Refractory CLL/SLL

• Status: Not yet recruiting
• Trial end date: 2024-01-01
• Target enrollment: 0
• Participant gender: All

Summary

The purpose of this study is to assess the efficacy and safety of APG-2575 single agent in patients with relapsed/refractory CLL/SLL.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Ascentage Pharma Group Inc.

Criteria

Inclusion Criteria:

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

1. Age ≥18 years old.

2. Pathologically confirmed CLL/SLL according to the 2018 revised IWCLL NCI-WG guidelines, subject with measurable lesions (peripheral blood B lymphocytes ≥5×10^9/L, or lymphadenopathy (baseline LDi≥1.5cm), or or splenomegaly due to CLL).

3. Expected survival is at least 12 weeks.

4. Refractory, recurrent, or intolerant to BTK inhibitors and immunochemotherapy,or first-line treatment with BTK inhibitors fails and is not suitable for immunochemotherapy.

5. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS): 0 -2.

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

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

8. Adequate renal and liver function.

9. Clinically significant adverse reactions related to previous treatments returned to less than grade 2.

10. Willingness by males, female patients of child bearing potential, and their partners to use contraception by effective methods throughout the treatment period and for at least three months following the last dose of study drug.

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

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

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

Exclusion Criteria:

Subjects 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 cell immunotherapy or autologous hematopoietic stem cell transplantation within 24 months.

2. Use the following drugs within 7 days before the first dose of study drug: moderately potent CYP3A inhibitors such as fluconazole, ketoconazole and clarithromycin; moderately potent CYP3A inducers such as rifampin, carbamazepine, phenytoin And St. John's wort.

3. Failure to recover adequately, at the discretion of the investigator, from prior surgical procedures. 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.

4. Received Bcl-2 inhibitor treatment.

5. Invasive NHL transformation or central nervous system (CNS) involvement has occurred.

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

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

8. Warfarin or other anticoagulants is required.

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

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

11. Within 2 years before entering the study, the subject had a history of active malignant tumors other than CLL / SLL, except that:

• Fully treated cervical carcinoma in situ;

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

• Confinement and resection of previously cured malignancies (or other treatment).

12. Has malabsorption syndrome or other conditions that are not suitable for enteral administration.

13. Uncontrolled other clinically significant symptoms, including but not limited to:

uncontrolled systemic infections (viruses, bacteria, or fungi), including but not limited to active hepatitis B (non-active hepatitis B subjects with HBV-SURFACE antigen positive but HBV-DNA≤2,000 copies/mL or 500 IU/ mL can be enrolled) ; Hepatitis C virus (HCV) antibody positive; human immunodeficiency virus (HIV) antibody positive; Febrile neutropenia occured within 1 week before administration.

14. Primary active autoimmune diseases and connective tissue diseases, such as active and uncontrolled primary autoimmune hemocytopenia, including autoimmune hemolytic anemia (AIHA) and primary immune thrombocytopenia (ITP).

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