Clinical Trial of TQB2825 Injection Combined Immunochemotherapy in Subjects With Diffuse Large B Cell Lymphoma

Inclusion Criteria:

• Subjects voluntarily participate in this study, sign the informed consent form, andhave good compliance;

• Age 18 to under 80 years old (calculated from the date of signing the informedconsent 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 InternationalPrognostic Index (IPI) scores of 2-5;

• A confirmed diagnosis of diffuse large B-cell lymphoma or grade 3b follicularlymphoma, in accordance with the 2022 World Health Organization (WHO) diagnosticcriteria, based on histology or cytology (including diffuse large B-celllymphoma-not otherwise specified and transformed from indolent lymphomas, notallowing for the following types or components: double-hit, triple-hit, orhigh-grade B-cell lymphoma-not otherwise specified, mediastinal large B-celllymphoma, T/histiocyte-rich large B-cell lymphoma, human herpesvirus 8 (HHV8)-positive/primary effusion lymphoma, Anaplastic lymphoma kinase (ALK)-positivelarge 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:

1. Combined with R-CHOP patients: previously untreated diffuse large B-celllymphoma patients, allowing for corticosteroid pre-treatment (with or withoutvincristine) or non-curative palliative local radiotherapy.

2. Combined with GemOx patients: patients with diffuse large B-cell lymphoma whohave received at least one line of systemic treatment (including at least oneline with CD20 monoclonal antibody) and are not suitable for hematopoietic stemcell transplantation or have failed treatment after transplantation orrelapsed, and whose disease progressed during the most recent treatment orrelapsed after completion of treatment or confirmed no objective response afteradequate 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 along diameter >10 mm based on CT cross-sectional imaging; Positron emissiontomography (PET)-computed tomography (CT) scan shows PET positivity;

• Laboratory tests meet the following criteria (not corrected with blood transfusionor hematopoietic growth factors within 14 days before screening):

1. Hemoglobin (HGB) ≥80g/L;

2. Absolute neutrophil count (NEUT) ≥1.0×10∧9/L;

3. Platelet count (PLT) ≥ 75×10∧9/L (if accompanied by bone marrow invasion,platelets ≥50×10∧9/L).

4. Total bilirubin (TBIL) ≤ 1.5 times the upper limit of normal (ULN);

5. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 ULN.If accompanied by liver metastasis, then ALT and AST ≤ 5 ULN;

6. Serum creatinine (CR) ≤ 1.5 ULN or estimated glomerular filtration rate ≥50ml/min by the Cockcroft-Gault formula.

7. 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 duringthe study and for 12 months after the study ends, with a negative serum or urinepregnancy test within 7 days before study enrollment; men must agree to useeffective contraceptive measures during the study and for 12 months after the studyends.

Exclusion Criteria:

• The subject has had or currently has other malignant tumors that occurred within 5years before the first dose of the study drug. The following two situations areeligible for enrollment: other malignant tumors that have been treated with singlesurgery and have achieved continuous 5 years of disease-free survival (DFS); curedcarcinoma in situ of the cervix, non-melanoma skin cancer, and superficial bladdertumors [Ta (non-invasive tumors), Tis (carcinoma in situ), and T1 (tumorsinfiltrating the basement membrane)];

• Adverse reactions from previous treatments have not recovered to a CommonTerminology Criteria for Adverse Events (CTCAE) v5.0 grade score of ≤1, except forgrade 2 alopecia, non-clinically significant and asymptomatic laboratoryabnormalities, and hypothyroidism stabilized with hormone replacement therapy, whichare deemed to have no safety risks by the investigator;

• Received major surgical treatment, significant traumatic injury within 4 weeksbefore the first dose, or expected to undergo major surgery during the studytreatment period, or has long-term unhealed wounds or fractures;

• Any subject with bleeding or bleeding events ≥CTC AE grade 3 within 4 weeks beforethe first dose;

• A history of arterial/venous thrombotic events within 6 months before the firstdose, such as cerebrovascular accidents (including transient ischemic attacks), deepvein thrombosis, and pulmonary embolism, or any other history of seriousthromboembolism (thrombosis from implanted venous access ports or catheters, orsuperficial vein thrombosis is not considered "serious" thromboembolism);

• Clinically significant uncontrollable pleural effusion requiring repeated drainage,ascites, moderate or greater pericardial effusion;

• Decompensated cirrhosis (Child-Pugh liver function rating of B or C) and activehepatitis (hepatitis B reference: positive HBsAg, and positive hepatitis B virus (HBV) DNA or detection value exceeding the lower limit of detection; hepatitis Creference: positive HCV antibody, and positive hepatitis C virus (HCV) RNA ordetection value exceeding the lower limit of detection); Note: Subjects withhepatitis B who are positive for HBsAg, regardless of whether their HBV DNA isdetectable, must continue antiviral treatment (nucleoside analogs recommended) andregularly monitor HBV DNA; for subjects with hepatitis B who are positive for HBcAbbut negative for HBsAg, regular monitoring of HBV DNA is required, and prophylacticantiviral treatment is recommended; for hepatitis C subjects, regular monitoring ofHCV RNA is required.

• Pulmonary diseases, including any of the following conditions:

1. Past or present non-infectious pneumonia requiring treatment withcorticosteroids (including but not limited to acute respiratory distresssyndrome, acute hypersensitivity pneumonia, drug-related pneumonia,bronchospasm, acute interstitial pneumonia, idiopathic pulmonary interstitialfibrosis, etc.);

2. Past or present chronic obstructive pulmonary disease (COPD), and forcedexpiratory volume in one second (FEV1) <60% (predicted value);

• Brain or mental abnormalities, including any of the following conditions:

1. A history of substance abuse that cannot be quit;

2. Accompanying or past central nervous system disease history, includingepileptic seizures, hemorrhagic/ischemic stroke, severe brain injury, dementia,Parkinson's disease, cerebellar disease, paralysis, aphasia, mental illness,consciousness disturbance, unexplained coma, neuropathy, organic brainsyndrome, etc.;

3. Brain MRI evidence indicating inflammatory lesions and/or vasculitis;

4. Cerebrovascular accidents, cerebral infarction, etc., within 6 months beforethe first dose;

• Major cardiovascular diseases, including any of the following conditions:

1. Heart failure of more than grade II according to the New York Heart Association (NYHA) standards or cardiac ultrasound examination: Left ventricular ejectionfraction (LVEF) <50%;

2. A history of clinically significant ventricular arrhythmias (such as sustainedventricular tachycardia, ventricular fibrillation, torsades de pointesventricular tachycardia) or arrhythmias requiring continuous antiarrhythmicdrug treatment;

3. A history of myocardial infarction, serious arrhythmias, unstable angina, etc.,within 6 months before the first dose;

4. The Fridericia-corrected QT interval (QTcF) is >450 milliseconds (msec) formales and >470 msec for females (if QTc is abnormal, it can be measured threetimes continuously with an interval of more than 2 minutes, and the averagevalue can be taken);

5. A history or family history of congenital long QT syndrome;

6. Hypertension that cannot be controlled with a combination of two drugs (atleast two measurement results are systolic pressure ≥160 mmHg, diastolicpressure ≥100 mmHg);

• Active or uncontrolled infections (≥CTC AE grade 2 infections), including bacterial,fungal, or viral infections (including but not limited to active pneumonia,syphilis, tuberculosis, and Coronavirus disease 2019 (COVID-19), etc. During thescreening period, Polymerase chain reaction (PCR) testing or two antigen tests forCOVID-19 must be performed (with an interval of at least 24 hours), and the testresults must be negative to be eligible. Subjects who do not meet the COVID-19infection eligibility criteria must fail the screening, and can only be re-screenedunder the following conditions: asymptomatic subjects at least 10 days after thefirst positive test result, or symptomatic subjects at least 10 days after the onsetof symptoms);

• Renal failure requiring hemodialysis or peritoneal dialysis, history of nephroticsyndrome;

• A history of immunodeficiency, including HIV positivity or other acquired orcongenital immunodeficiency diseases;

• Having or having had autoimmune diseases that require treatment, subjects receivingstable replacement therapy for hypothyroidism, and type 1 diabetes can be enrolled.

• Prepared for or having received organ transplantation, or having obvious host-graftreactions, or having received allogeneic hematopoietic stem cell transplantation inthe past;

• Need for systemic immunosuppressive treatment, including but not limited to: use ofcyclosporine, tacrolimus, etc., within 4 weeks before the first dose, receivinghigh-dose glucocorticoid therapy (prednisone >30 mg/day or equivalent dose of otherglucocorticoids), or receiving any other immunosuppressive treatment. Subjectsreceiving inhaled or local corticosteroid treatment, or those who have beenreceiving a stable dose of prednisone <10 mg/day or equivalent dose of otherglucocorticoids for systemic treatment for at least 4 weeks before the first dose,or those receiving prophylactic medication to prevent infusion reactions before theadministration of the trial medication can be enrolled;

• Known or suspected history of hemophagocytic lymphohistiocytosis (HLH);

• For relapsed/refractory patients, previous anti-tumor treatments:

1. Received chemotherapy, immunotherapy, monoclonal antibody treatment within 4weeks before the first dose, radiotherapy or small molecule targeted drugswithin 2 weeks, or still within the 5 half-lives of the drug (the shortestappearing time shall prevail), the washout period is calculated from the end ofthe last treatment;

2. Received traditional Chinese medicine (including Compound Eschar Capsules,Kangai Injection, Kanglaite Capsules/Injection, Aidi Injection, Yanzaizi OilInjection/Capsules, Xiaocaiping Tablets/Injection, Huachansu Capsules, etc.)with anti-tumor indications approved by the National Medical ProductsAdministration (NMPA) in the drug instructions within 2 weeks before the firstdose;

3. Previously used other antibody drugs targeting both CD3 and CD20;

4. Received Chimeric antigen receptor T (CAR-T) treatment or other immune celltherapy, or autologous hematopoietic stem cell transplantation (auto-HSCT)within 3 months before the first dose;

5. Previously received R-GemOx or GemOx treatment;

• Known allergies to excipient components of the study drug.

• Participated in and used other anti-tumor clinical trial drugs within 4 weeks or 5half-lives before the first dose.

• In the judgment of the investigator, there are situations that seriously endangerthe safety of the subject or affect the subject's completion of the study.