Pirtobrutinib in Combination With Rituximab, Gemcitabine, Oxaliplatin With or Without Polatuzumab Vedotin in Covalent BTK Inhibitor-Pretreated Relapsed/Refractory Diffuse Large B-Cell Lymphoma

Prior treatment

• Major surgery within 4 weeks prior to treatment (excluding vascular access placement or biopsy)

Other illness

• Contraindications or hypersensitivity to any drug in the combination regimen
• Any life-threatening illness, medical condition, or organ system dysfunction that, in the investigator's judgment, may compromise patient safety or compliance with study procedures
• Poorly controlled cardiac clinical symptoms or diseases, including:
  • NYHA Class II or higher heart failure ii. Unstable angina iii. Myocardial infarction within 1 year iv. Clinically significant supraventricular or ventricular arrhythmias requiring treatment/intervention
• Active hemorrhage
• Poorly controlled systemic bacterial, viral, fungal, or parasitic infections (excluding fungal nail infections), or other clinically significant active diseases that render patients unsuitable for trial participation per investigator assessment
• Patients with:Active chronic hepatitis B or C.Positive HBsAg and/or HBcAb or HCV antibodies at screening must demonstrate HBV DNA ≤2,500 copies/mL (or 500 IU/mL) to exclude active HBV/HCV infection requiring treatment.HBsAg/HBcAb-positive patients must receive antiviral prophylaxis.
  • HIV-infected patients and/or AIDS patients
• Inability to swallow tablets, malabsorption syndrome, or any gastrointestinal disorder/ dysfunction that may impair drug absorption
• Psychiatric disorders or inability to provide informed consent
• Any other condition deemed unsuitable for study participation by the investigator

Other

• DLBCL with central nervous system (CNS) or meningeal involvement
• Histologically transformed DLBCL
• Lactating or pregnant women

• Histologically confirmed DLBCL (2016 WHO criteria) of MCD, BN2, N1 subtypes, double-expressor, intravascular large B-cell lymphoma, or other BTK-sensitive subtypes
• Disease progression/relapse after covalent BTK inhibitor therapy
• ≥1 measurable lesion (nodal \>15mm/extranodal \>10mm) on PET/CT within 28 days
• Eastern Cooperative Oncology Group (ECOG) 0-2
• age ≥18 years
• Adequate organ function:
  • ANC ≥0.5×10⁹/L ；Platelets ≥50×10⁹/L (transfusion-independent)；Bilirubin ≤1.5×ULN; ALT/AST ≤2.5×ULN；Cr ≤1.5×ULN or CrCl ≥30mL/min；LVEF ≥50% (NYHA class \<III)
• Life expectancy \>3 months
• Sign the written ICF, and be able to comply with the visits and related procedures stipulated in the protocol;
• Female subjects of childbearing potential or male subjects with female partners of childbearing potential must use effective contraception throughout the treatment period and for 90 days after the last treatment.