A Study of GNC-038, a Tetra-specific Antibody, in Participants With R/R Diffuse Large B-cell Lymphoma (DLBCL)

Inclusion Criteria:

1. he participants could understand and sign the informed consent form, and mustparticipate voluntarily;

2. No gender limit;

3. Age: ≥18 years old and ≤75 years;

4. Expected survival time ≥ 3 months;

5. Has suffered from Diffuse Large B-cell lymphoma (DLBCL) confirmed by histology orcytology;

6. a. Those who have recurrent or refractory Diffuse Large B-cell lymphoma (DLBCL). b. Recurrent or refractory participants that are, determined by the investigators,not applicable/tolerated to other treatments. Recurrent and refractory are defined as follows: Recurrent is the progression of disease after adequate treatment to remission, withat least one regimen containing rituximab. Refractory refers to failure to respond to adequate treatment with rituximabcontaining regimen (combination chemotherapy or monotherapy) or disease progressionduring treatment/within 6 months of completion of adequate treatment.

"Adequate treatment with rituximab regimen" refers to the completion of rituximabcombined with chemotherapy based on pathological type and disease stagerequirements, or rituximab monotherapy with 375 mg/m2 injections at least 4 times aweek. "Progress during treatment" requires completion of at least one cycle ofrituximab plus chemotherapy or monotherapy if progress during induction therapy; Atleast one injection is completed if progress is made during maintenance therapy. "Mitigation" includes complete and partial mitigation.

7. There are measurable lesions during the screening period (any long diameter of lymphnode lesions ≥ 1.5 cm or any long diameter of extra-nodal lesions greater than 1.0cm);

8. Physical fitness score ECOG≤2；

9. The toxicity of the previous anti-tumor therapy has been restored to the level ≤1defined by NCI-CTCAE v5.0 (the investigators considered indicators that might beassociated with the disease, such as anemia, and excluded toxicities that theinvestigators considered to be of no safety risk, such as alopecia, grade 2peripheral neurotoxicity, and hypothyroidism stabilized by hormone replacementtherapy);

10. The organ function within 7 days prior to the first administration meets thefollowing requirements:

• Bone marrow function: In the case of no blood transfusion, no use of G-CSF (nouse of long-acting whitening needles within 2 weeks) and drug correction within 7 days prior to screening, the absolute value of neutrophil count (ANC) ≥1.0×109/L (participants with bone marrow infiltration ≥0.5×109/L); Hemoglobin ≥80 g/L (for participants with bone marrow infiltration, ≥70 g/L); Plateletcount ≥50×109/L;

• Liver function: In the absence of hepatoprotective drugs for correction within 7 days prior to screening, total bilirubin (TBIL) ≤ 1.5 ULN (TBIL ≤3 ULN inparticipants with Gilbert's syndrome), transaminase (AST/ALT) ≤ 2.5 ULN (participants with tumor infiltration in the liver ≤5.0 ULN);

• Kidney function: creatinine (Cr) ≤ 1.5 ULN and creatinine clearance (Ccr) ≥ 50mL/min (according to the Cockcroft and Gault formula);

• Routine urine / 24h urine protein quantification: qualitative urine protein ≤1+ (if qualitative urine protein ≥2+, 24h urine protein < 1g can be included);

• Cardiac function: left ventricular ejection fraction ≥50%;

• Coagulation function: fibrinogen (FIB) ≥1.5g/L; activated partialthromboplastin time (APTT) ≤1.5×ULN; prothrombin time (PT) ≤1.5×ULN.

11. Female participants with fertility or male participants whose partner(s) are fertilemust take effective contraceptive measures from 7 days prior to the firstadministration to 24 weeks after the administration. Female participants withfertility must have a negative serum/urine pregnancy test in 7 days prior to thefirst dose.

12. The subjects are able and willing to follow the visits, treatment plans, laboratorytests, and other study-related procedures specified in the study protocol.

Exclusion Criteria:

1. Has grade 3 or above lung disease defined according to NCI-CTCAE v5.0; Patients withcurrent interstitial lung disease (ILD) (except those who have recovered fromprevious interstitial pneumonia;

2. Active infections requiring systemic treatment, such as severe pneumonia,bacteremia, sepsis, etc;

3. Active tuberculosis;

4. Participants at risk of active autoimmune diseases, such as: systemic lupuserythematosus, systemic treatment of psoriasis, rheumatoid arthritis, inflammatorybowel disease, and hashimoto's thyroiditis, etc., with the exception of type Idiabetes, only replacement therapy can control the hypothyroidism, no systemictreatment of skin disease (such as vitiligo, psoriasis), B cells caused byautoimmune disease;

5. Complicated with other malignant tumors within 5 years prior to GNC-038 treatment,except for non-melanoma skin cancer in situ, superficial bladder cancer, cervicalcancer in situ, gastrointestinal intramucosal cancer, breast cancer and localizedprostate cancer that have been cured and have not recurred within 5 years;

6. HBsAg or HBcAb positive and HBV-DNA test ≥ULN; HCV antibody positive andHCV-RNA≥ULN; HIV antibody positive;

7. Participants with poorly controlled hypertension by antihypertensive drugs (systolicblood pressure>150 mmHg or diastolic blood pressure>100 mmHg);

8. History of severe heart disease, including but not limited to:

• There are serious cardiac rhythm or conduction abnormalities, such asventricular arrhythmias, III grade atrioventricular block, which requireclinical intervention;

• Participants with prolonged QT interval (male QTc > 450 msec or female QTc > 470 msec);

• Acute coronary syndrome, congestive heart failure, aortic dissection, stroke,or other grade 3 or above cardiovascular and cerebrovascular events occurredwithin 6 months before the first administration;

• New York Heart Association (NYHA) grade II, III or IV congestive heart failure;

9. Patients with a history of allergy to recombinant humanized antibodies or to anyexcipient component of GNC-038;

10. Pregnant or breastfeeding women;

11. There is an invasion of the central nervous system;

12. Has undergone major surgery within 28 days prior to the administration of thisstudy, or planned to undergo major surgery during the study period (except forsurgery such as puncture or lymph node biopsy);

13. Has accepted organ transplantation or allogeneic hematopoietic stem celltransplantation (ALLo-HSCT);

14. Has accepted autologous hematopoietic stem cell transplantation (Auto-HSCT) within 12 weeks prior to GNC-038 treatment;

15. Currently using immunosuppressive agents within 2 weeks prior to GNC-038 treatment,including but not limited to: Cyclosporine, tacrolimus, etc.; receiving high-doseglucocorticoids within 2 weeks prior to GNC-038 treatment (longer than 14 days, astable dose of >30 mg of prednisone or other glucocorticoids at the same dose perday);

16. Has received radiotherapy within 4 weeks prior to GNC-038 treatment;

17. Has received anti-CD20 or anti-CD79b treatment within 4 weeks prior to GNC-038treatment, and continued to respond;

18. Has received chemotherapy, small molecule targeted drugs within 2 weeks prior toGNC-038 treatment;

19. Has received CAR-T treatment within 12 weeks prior to GNC-038 treatment.

20. Has participated in any other clinical trials within 4 weeks prior to GNC-038treatment;

21. Other conditions that the investigator believes that it is not suitable forparticipating in this clinical trial.