Pirtobrutinib+Sonrotoclax（PS) Regimen in the Treatment of B-Cell Lymphoma

Inclusion Criteria:

* Cohort 1: Histologically transformed DLBCL

  1. Histopathologically confirmed histologically transformed DLBCL, including transformation from indolent lymphomas such as CLL, WM, FL, and MZL.
  2. Whole-body PET/CT performed within 28 days prior to study enrollment demonstrating at least one measurable lesion in two perpendicular dimensions (longest diameter \>15 mm for nodal lesions, or longest diameter \>10 mm for extranodal lesions).
  3. Except patients with Richter transformation, patients transformed from MZL, FL, WM, etc., must have received at least one line of systemic anti-lymphoma therapy either during the indolent phase or after transformation.

Cohort 2: Relapsed/refractory CLL/SLL

1. Histopathologically confirmed relapsed/refractory CLL/SLL.
2. Disease relapse or refractoriness after at least one line of systemic anti-lymphoma therapy, which may include a BTK inhibitor.

Cohort 3: Relapsed/refractory MZL

1.Histopathologically confirmed relapsed/refractory MZL. 2.Received systemic therapy containing an anti-CD20 monoclonal antibody or a BTK inhibitor.

3.Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-2. 4.Age ≥ 18 years. 5.Adequate organ and bone marrow function defined as follows:

1. Hematologic function (assessed within 7 days prior to Cycle 1 Day 1 \[C1D1\]): a. Absolute neutrophil count (ANC) ≥ 0.5 × 10⁹/L. Patients with values below this threshold may be eligible if there is documented bone marrow involvement impairing hematopoiesis. b. Platelet count ≥ 50 × 10⁹/L without transfusion support. Patients with values below this threshold may be eligible if there is documented bone marrow infiltration impairing hematopoiesis. c. If transfusions are administered to treat thrombocytopenia or anemia, the patient must demonstrate a response to transfusion support.
2. Coagulation function: Activated partial thromboplastin time (aPTT), prothrombin time (PT), or international normalized ratio (INR) ≤ 1.5 × upper limit of normal (ULN).
3. Hepatic function: Serum total bilirubin (TBIL) ≤ 1.5 × ULN; alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN.
4. Renal function: Serum creatinine (Cr) ≤ 1.5 × ULN or creatinine clearance (CCr) ≥ 30 mL/min.
5. Cardiac function: New York Heart Association (NYHA) functional class less than Class III; ejection fraction ≥ 50% on echocardiogram.

6.Estimated survival \> 3 months. 7.Able to provide written informed consent and comply with protocol-specified study visits and procedures.

8.Female subjects of childbearing potential, or male subjects whose female partners are of childbearing potential, must utilize effective contraceptive measures throughout the treatment period and for 90 days after the last dose of study treatment.

Exclusion Criteria:

1. DLBCL with central nervous system or leptomeningeal involvement;
2. Prior treatment with a non-covalent BTK inhibitor;
3. Prior treatment with immune checkpoint inhibitors;
4. Contraindication or hypersensitivity to any drug in the combination treatment regimen;
5. Concurrent other malignancies requiring treatment or intervention;
6. Major surgery within 4 weeks prior to treatment (excluding vascular access catheterization or biopsy);
7. Any life-threatening disease, medical condition or organ dysfunction that, in the Investigator's opinion, may compromise patient safety or compliance with study procedures;
8. Uncontrolled clinical cardiac signs or diseases, including: i. Heart failure of NYHA Class ≥ II ii. Unstable angina pectoris iii. Myocardial infarction within the past 12 months iv. Clinically significant supraventricular or ventricular arrhythmias requiring treatment or intervention;
9. Patients with active bleeding;
10. Active and uncontrolled systemic bacterial, viral, fungal or parasitic infection (excluding fungal nail infection), or other clinically significant active disease process rendering the patient unsuitable for trial participation as judged by the Investigator.
11. Patients with active chronic hepatitis B or active hepatitis C. Patients positive for Hepatitis B surface antigen (HBsAg) and/or Hepatitis B core antibody (HBcAb), or Hepatitis C virus (HCV) antibody at screening must undergo further Hepatitis B virus (HBV) DNA testing (≤2500 copies/mL or ≤500 IU/mL) to rule out active hepatitis B or active hepatitis C requiring treatment before enrollment. Nevertheless, eligible patients with positive HBsAg and/or HBcAb must receive anti-hepatitis B antiviral therapy.
12. Patients infected with Human Immunodeficiency Virus (HIV) and/or patients with acquired immunodeficiency syndrome (AIDS);
13. Inability to swallow tablets, presence of malabsorption syndrome, or any other gastrointestinal disease or dysfunction that may affect absorption of the study drug;
14. Pregnant or lactating women;
15. Patients with psychiatric disorders or those unable to provide informed consent;
16. Patients deemed unsuitable for participation in this study by the Investigator.