The Study of ICP-248 in Patients With Mature B-cell Malignancies

Inclusion Criteria:

1. Age ≥ 18 and ≤ 80 years.

2. One of the following histopathologically and/or flow cytometry-confirmed diseasesaccording to the 2016 World Health Organization (WHO) classification criteria forlymphohematopoietic neoplasms or meeting the International Workshop on ChronicLymphocytic Leukemia (iwCLL) criteria: Histopathologically and/or flowcytometry-confirmed CLL/SLL; Pathologically confirmed MCL; Pathologically confirmedB-NHL, including diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL),marginal zone lymphoma (MZL), and lymphoplasmacytic lymphoma (LPL).

3. Relapsed disease or refractory disease

4. For subjects with B-NHL: Patients must have measurable diseasePatients with anEastern Cooperative Oncology Group (ECOG) performance status (PS) score of ≤ 2 and alife expectancy of ≥ 6 months.

5. Adequate hematologic function.

6. Patients with basically normal coagulation function.

7. Patients with adequate hepatic, renal, pulmonary and cardiac functions.

8. CLL/SLL Patients with an absolute lymphocyte count ≥ 50 x 109/L and any lymph nodes ≥ 5 cm in the long diameter or CLL/SLL or B-NHL patients with any lymph nodes ≥ 10cm in the long diameter will be enrolled in the study after weighing the risks andbenefits with the sponsor's MM.

9. Female patients of childbearing potential must have a negative blood pregnancy testwithin 7 days prior to the first dose of the investigational product; patients ofchildbearing potential (males and females) must agree to use a reliable birthcontrol method (hormonal or barrier method or abstinence) with their partners fromsigning the ICF until 90 days after the last dose.The last ICP- 248 dose or withinone month after the last dose of Orelabrutinib Or within 12 months after the lastdose of Rituximab (whichever is longer).

10. Subjects are able to communicate with the investigator well and to complete thestudy as specified in the study.

11. Before the trial, the subjects shall understand the nature, significance, possiblebenefits, inconveniences and potential risks, as well as the study procedures of thetrial in detail and voluntarily sign the written Informed Consent Form (ICF).

12. Subjects with CLL/SLL must have an indication for treatment as judged by theinvestigator.

Exclusion Criteria:

1. Prior malignancy (other than the disease under study) within 2 years before studyentryKnown

2. Central nervous system involvement by lymphoma/leukemia

3. Underlying medical conditions that, in the investigator's opinion, will render theadministration of the investigational product hazardous or obscure theinterpretation of the safety or efficacy results.

4. Prior autologous stem cell transplant (unless ≥ 3 months after transplant); or priorchimeric cell therapy (unless ≥ 3 months after cell infusion).

5. Received a BCL-2 inhibitor prior to initial use of the investigational drug and didnot achieve disease remission or disease recurrence/progression on treatment;Disease recurrence/progression after stopping or ending BCL-2 inhibitor therapy isacceptable.

6. A history of allogeneic stem cell transplantation.

7. Anti-cancer therapy within 14 days prior to the first dose of the investigationalproduct

8. An interval of less than 5 half-lives from the last dose of a strong CYP3A inhibitoror inducer (chemical agent, traditional Chinese medicine and dietary supplement) tothe first dose of the investigational product, or a plan to use concurrentlymedications, dietary supplements or food (e.g., grapefruit or grapefruit juice) withstrong CYP3A inhibitory or inductive effect during study participation.

9. Patients who have undergone major organ surgery (excluding aspiration biopsy) orsignificant trauma within 28 days prior to the first dose of the investigationalproduct, or who require elective surgery during the trial.

10. Patients who have received a live attenuated vaccine within 28 days prior to thefirst dose of the investigational product (except for vaccination to prevent a majorpublic health event).

11. Presence of active infection that currently requires intravenous systemicanti-infective therapy.

12. Patients with active hepatitis B or C virus infection.

13. History of immunodeficiency, including a positive human immunodeficiency virus (HIV)antibody test.

14. History of significant cardiovascular disease

15. Patients with previous or concomitant central nervous system disordersHistory orcurrent evidence of severe interstitial lung disease.

16. ≥ Grade 2 toxicity due to prior anti-cancer therapy at enrollment (except foralopecia, ANC, hemoglobin and PLT). For ANC, hemoglobin and PLT, please follow theinclusion criteria.

17. History of severe bleeding disorder

18. Known alcohol or drug dependence.

19. Presence of mental disorders or poor compliance.

20. Female patients who are pregnant or lactating.

21. Unable to swallow tablets or disease significantly affecting gastrointestinalfunction.

22. Hypersensitivity to the active substance or excipients of ICP-248 tablets orOrelabrutinib tablets (only applicable to subjects in cohort G/H/J/K).Severeallergic reaction or intolerance to murine monoclonal antibodies or murine products.

23 Invasive mantle cell lymphoma, such as mother cell subtypes, polymorphic subtypes, or Ki-67 proliferation index>50%, must be discussed with the sponsor's medical monitor regarding patient benefits and risks before being included in this study.