Pirtobrutinib, Lisaftoclax, and Rituximab in the Treatment of R/R DLBCL

Inclusion Criteria:

1. ≥18 years old.
2. Capable of understanding and voluntarily signing written informed consent.
3. ECOG performance 0 \~ 3.
4. Anticipated survival ≥3 months
5. Histologically or cytologically confirmed DLBCL.
6. PET-CT-defined measurable disease with a short axis diameter of ≥1.5 cm.
7. Have received at least one prior line of systemic therapy for DLBCL.
8. Resolution of any prior treatment-related non-hematologic toxicities to Grade ≤1 or baseline.
9. Adequate Bone Marrow and Organ Function, defined as:

   Bone Marrow Function: ANC≥1.5 × 10⁹/L, Platelets ≥80 × 10⁹/L, Hemoglobin ≥80 g/L Hepatic Function: Total bilirubin ≤1.5 × ULN (≤3.0 × ULN if liver metastases present); AST/SGOT and ALT/SGPT ≤2.5 × ULN (≤5.0 × ULN if liver metastases present) Coagulation: INR and aPTT≤1.5 × ULN Renal Function: Serum creatinine ≤1.5 × ULN or estimated creatinine clearance (CrCl) ≥60 mL/min;
10. Subjects with childbearing or childbearing potential must be willing to practice birth control from the date of registration in this study to the follow-up period of the study.
11. Able to swallow tablets/capsules without difficulty.
12. Adhere to scheduled visits, treatment plans, laboratory tests, and other study procedures.

Exclusion Criteria:

1. Prior treatment failure or resistance to pirtobrutinib or BCL2 inhibitors.
2. Prior Anticancer Therapy:Chemotherapy, radiotherapy, immunotherapy, or antibody-based anticancer therapy within the specified washout period.Traditional Chinese herbal medicine with antitumor indications.Small-molecule targeted therapy within 2 weeks before study treatment initiation. ADCs or cytotoxic therapy within 10 weeks before study treatment initiation.
3. Participation in another investigational drug study within 4 weeks prior to the first dose of study treatment.
4. Systemic corticosteroid therapy (\>5 days within 14 days prior to treatment) at doses exceeding \>10 mg/day dexamethasone (or equivalent) for CNS disease control.
5. Requiring ongoing anticancer therapy.
6. Uncontrolled or Severe Cardiovascular Disease,
7. Active infection requiring IV antibiotics or systemic antimicrobial therapy.
8. Active HBV/HCV:Exceptions. Inactive HBsAg carriers, HBV patients with sustained viral suppression (HBV-DNA \< LLOD),HCV-cured patients are allowed.
9. Clinically significant abnormalities affecting drug absorption or prior total gastrectomy/gastric banding.
10. History of hemorrhagic diathesis or requirement for long-term oral anticoagulation.
11. Prior allogeneic hematopoietic stem cell transplantation (HSCT) or planned allogeneic HSCT.
12. Women who are pregnant or breastfeeding.
13. Known allergy to the study drug or its excipients.
14. Active psychiatric illness or history of alcohol/drug abuse .
15. Any uncontrolled illness, organ dysfunction, or medical condition that, in the investigator's judgment, jeopardizes patient safety or adherence to study procedures.
16. Other conditions deemed inappropriate for study participation by the investigator.