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

Inclusion criteria

• ≥18 years old.
• Capable of understanding and voluntarily signing written informed consent.
• ECOG performance 0 ~ 3.
• Anticipated survival ≥3 months
• Histologically or cytologically confirmed DLBCL.
• PET-CT-defined measurable disease with a short axis diameter of ≥1.5 cm.
• Have received at least one prior line of systemic therapy for DLBCL.
• Resolution of any prior treatment-related non-hematologic toxicities to Grade ≤1 or baseline.
• 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;

• 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.
• Able to swallow tablets/capsules without difficulty.
• Adhere to scheduled visits, treatment plans, laboratory tests, and other study procedures.

Exclusion criteria

• Prior treatment failure or resistance to pirtobrutinib or BCL2 inhibitors.
• 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.
• Participation in another investigational drug study within 4 weeks prior to the first dose of study treatment.
• Systemic corticosteroid therapy (>5 days within 14 days prior to treatment) at doses exceeding >10 mg/day dexamethasone (or equivalent) for CNS disease control.
• Requiring ongoing anticancer therapy.
• Uncontrolled or Severe Cardiovascular Disease,
• Active infection requiring IV antibiotics or systemic antimicrobial therapy.
• Active HBV/HCV:Exceptions. Inactive HBsAg carriers, HBV patients with sustained viral suppression (HBV-DNA < LLOD),HCV-cured patients are allowed.
• Clinically significant abnormalities affecting drug absorption or prior total gastrectomy/gastric banding.
• History of hemorrhagic diathesis or requirement for long-term oral anticoagulation.
• Prior allogeneic hematopoietic stem cell transplantation (HSCT) or planned allogeneic HSCT.
• Women who are pregnant or breastfeeding.
• Known allergy to the study drug or its excipients.
• Active psychiatric illness or history of alcohol/drug abuse .
• Any uncontrolled illness, organ dysfunction, or medical condition that, in the investigator's judgment, jeopardizes patient safety or adherence to study procedures.
• Other conditions deemed inappropriate for study participation by the investigator.