Phase Ib/II Clinical Trial of TQB2825 Injection Combined Immunochemotherapy in Subjects With Diffuse Large B Cell Lymphoma
To explore the efficacy and safety of TQB2825 injection combined immunochemotherapy in subjects with untreated or R/R DLBCL. The efficacy evaluation indicators are objective response rate (ORR), complete response rate (CR rate),progression free survival (PFS), duration of response (DOR) and overall survival(OS). The safety evaluation indicators are dose-limiting toxicity (DLT) , maximum tolerated dose (MTD)and recommended phase II dose (RP2D).
• Subjects voluntarily participate in this study, sign the informed consent form, and have good compliance;
• Age 18 to under 80 years old (calculated from the date of signing the informed consent form);
• Eastern Cooperative Oncology Group (ECOG) score of 0 to 2;
• Life expectancy greater than 12 weeks;
• In the dose expansion phase, previously untreated patients with International Prognostic Index (IPI) scores of 2-5;
• A confirmed diagnosis of diffuse large B-cell lymphoma or grade 3b follicular lymphoma, in accordance with the 2022 World Health Organization (WHO) diagnostic criteria, based on histology or cytology (including diffuse large B-cell lymphoma-not otherwise specified and transformed from indolent lymphomas, not allowing for the following types or components: double-hit, triple-hit, or high-grade B-cell lymphoma-not otherwise specified, mediastinal large B-cell lymphoma, T/histiocyte-rich large B-cell lymphoma, human herpesvirus 8 (HHV8)-positive/primary effusion lymphoma, Anaplastic lymphoma kinase (ALK)-positive large B-cell lymphoma, Burkitt's lymphoma, and Hodgkin's lymphoma, etc.);
• Immunophenotypic analysis shows that the tumor is CD20 positive;
• Previous treatment meets the following criteria:
‣ Combined with R-CHOP patients: previously untreated diffuse large B-cell lymphoma patients, allowing for corticosteroid pre-treatment (with or without vincristine) or non-curative palliative local radiotherapy.
⁃ Combined with GemOx patients: patients with diffuse large B-cell lymphoma who have received at least one line of systemic treatment (including at least one line with CD20 monoclonal antibody) and are not suitable for hematopoietic stem cell transplantation or have failed treatment after transplantation or relapsed, and whose disease progressed during the most recent treatment or relapsed after completion of treatment or confirmed no objective response after adequate treatment.
• According to the 2014 Lugano criteria, there is at least one measurable lesion, i.e., lymph node lesions with a long diameter \>15 mm or extranodal lesions with a long diameter \>10 mm based on CT cross-sectional imaging; Positron emission tomography (PET)-computed tomography (CT) scan shows PET positivity;
• Laboratory tests meet the following criteria (not corrected with blood transfusion or hematopoietic growth factors within 14 days before screening):
‣ Hemoglobin (HGB) ≥80g/L;
⁃ Absolute neutrophil count (NEUT) ≥1.0×10∧9/L;
⁃ Platelet count (PLT) ≥ 75×10∧9/L (if accompanied by bone marrow invasion, platelets ≥50×10∧9/L).
⁃ Total bilirubin (TBIL) ≤ 1.5 times the upper limit of normal (ULN);
⁃ Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 ULN. If accompanied by liver metastasis, then ALT and AST ≤ 5 ULN;
⁃ Serum creatinine (CR) ≤ 1.5 ULN or estimated glomerular filtration rate ≥50 ml/min by the Cockcroft-Gault formula.
⁃ Prothrombin time (PT), activated partial thromboplastin time (APTT), international normalized ratio (INR) ≤ 1.5×ULN (not on anticoagulant therapy);
• Women of childbearing age must agree to use effective contraceptive measures during the study and for 12 months after the study ends, with a negative serum or urine pregnancy test within 7 days before study enrollment; men must agree to use effective contraceptive measures during the study and for 12 months after the study ends.