Phase Ib/II Study of GNC-038 Injection in Patients With Relapsed or Refractory Non-Hodgkin's Lymphoma

Inclusion Criteria:

1. The subject can understand the informed consent form, voluntarily participatein and sign the informed consent form;

2. Both sexes;

3. Age: ≥18 years and ≤75 years;

4. Expected survival time ≥3 months;

5. Patients with histologically confirmed non-Hodgkin's lymphoma;

6. Patients with relapsed and refractory non-Hodgkin's lymphoma (R/R NHL).Specifically include: Patients who have experienced at least a second-linetreatment failure; Investigator-determined patients with relapsed or refractorynon-Hodgkin's lymphoma who had no or were ineligible/intolerant to othertherapies.

7. The presence of measurable lesions (any length diameter of lymph node lesions ≥1.5cm or any length diameter of extranodal lesions > 1.0cm) during thescreening period;

8. ECOG score ≤2;

9. Adverse reactions of previous antitumor therapy returned to CTCAE 5.0 grade ≤1 (except for indicators that the investigator considered to be related to thedisease, such as anemia, and toxicity that the investigator judged to be of nosafety risk, such as hair loss, grade 2 peripheral neurotoxicity, and stablehypothyroidism after hormone replacement therapy);

10. The organ function level before the first administration met the followingrequirements: Bone marrow function: In the absence of blood transfusion within 7 days prior to screening, G-CSF (no long-acting white needle within 2 weeks),and medication correction: Absolute neutrophil count (ANC) ≥1.0×10^9/L (≥0.5×10^9/L for subjects with bone marrow infiltration); Hemoglobin ≥80 g/L (≥70g/L for subjects with bone marrow infiltration); Platelet count ≥75×10^9/L;Liver function: Total bilirubin ≤1.5 ULN (≤3 ULN for Gilbert's syndrome) andtransaminase (AST/ALT) ≤2.5 ULN (≤5.0 ULN for subjects with tumor invasivechanges in the liver) without correction with hepatoprotective agents within 7days before screening; Kidney function: creatinine (Cr) ≤1.5 ULN and creatinineclearance (Ccr) ≥50 ml/min (according to Cockcroft and Gault formula);

• Urine routine / 24-hour urinary protein quantification: urine proteinqualitative ≤1+ (if urine protein qualitative ≥2+, 24-hour urinary protein < 1gcan be enrolled);

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

• Coagulation function: fibrinogen ≥1.5g/L; Activated partial thromboplastin time (APTT) ≤1.5 ULN; Prothrombin time (PT) ≤1.5 ULN.

11. Fertile female subjects or male subjects with a fertile partner must use highlyeffective contraception from 7 days before the first dose until 12 weeks afterdiscontinuation of treatment. Fertile female subjects must have a negativeserum/urine pregnancy test within 7 days before the first dose;

12. Subjects are able and willing to comply with the study protocol for visits,treatment plans, laboratory tests, and other study-related procedures.

Exclusion Criteria:

1. Pulmonary disease grade ≥3 as defined by NCI-CTCAE V5.0; Patients with currentinterstitial lung disease (ILD) (except those who have recovered from previousinterstitial pneumonia);

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

3. Active pulmonary tuberculosis;

4. Patients with active autoimmune diseases, such as: Systemic lupuserythematosus, systemic treatment of psoriasis, rheumatoid arthritis,inflammatory bowel disease, and hashimoto's thyroiditis, etc., with theexception of type I diabetes, only replacement therapy can control thehypothyroidism, no systemic treatment of skin disease (e.g., vitiligo,psoriasis), B cells caused by autoimmune disease;

5. Other malignant tumors were complicated within 5 years before the firstadministration, except non-melanoma skin cancer in situ, superficial bladdercancer, cervical cancer in situ, gastrointestinal intramucosal cancer, breastcancer, localized prostate cancer that had been cured and had not recurredwithin 5 years.

6. HBsAg positive or HBcAb positive, and HBV-DNA detection ≥ the lower limit ofthe detection value; HCV antibody positive and HCV-RNA≥ lower limit ofdetection value; HIV antibody positive;

7. Poorly controlled hypertension (systolic blood pressure & GT; 160 mmHg ordiastolic blood pressure & GT; 100 mmHg);

8. History of serious cardiovascular and cerebrovascular diseases, including butnot limited to:

• Severe cardiac rhythm or conduction abnormalities, such as ventriculararrhythmias requiring clinical intervention, degree ⅲ atrioventricular block,etc.; At rest, the QT interval is prolonged (QTc > 450 msec in men or QTc > 470msec in women); Acute coronary syndrome, congestive heart failure, aorticdissection, stroke, or other grade 3 or higher cardiovascular andcerebrovascular events occurring within 6 months before the first dose;

• The presence of New York Heart Association (NYHA) class II or higher heartfailure;

9. Patients with a history of allergy to recombinant humanized antibodies or toany excipient components of GNC-038;

10. Women who are pregnant or breastfeeding;

11. Patients with central nervous system invasion;

12. Patients who underwent major surgery within 28 days before the administrationof the drug in this study, or who were to undergo major surgery during thestudy period (except for puncture or lymph node biopsy);

13. Previous organ transplantation or allogeneic hematopoietic stem celltransplantation (allo-HSCT);

14. Autologous hematopoietic stem cell transplantation (Auto-HSCT) was performedwithin 12 weeks before starting GNC-038 treatment.

15. Pulmonary disease grade ≥3 as defined by NCI-CTCAE V5.0; Patients with currentinterstitial lung disease (ILD) (except those who have recovered from previousinterstitial pneumonia);

16. Active infections that require systemic treatment, such as severe pneumonia,bacteremia, sepsis, etc.;

17. Active pulmonary tuberculosis;

18. Patients with active autoimmune diseases, such as: Systemic lupuserythematosus, systemic treatment of psoriasis, rheumatoid arthritis,inflammatory bowel disease, and hashimoto's thyroiditis, etc., with theexception of type I diabetes, only replacement therapy can control thehypothyroidism, no systemic treatment of skin disease (e.g., vitiligo,psoriasis), B cells caused by autoimmune disease;

19. Other malignant tumors were complicated within 5 years before the firstadministration, except non-melanoma skin cancer in situ, superficial bladdercancer, cervical cancer in situ, gastrointestinal intramucosal cancer, breastcancer, localized prostate cancer that had been cured and had not recurredwithin 5 years.

20. HBsAg positive or HBcAb positive, and HBV-DNA detection ≥ the lower limit ofthe detection value; HCV antibody positive and HCV-RNA≥ lower limit ofdetection value; HIV antibody positive;

21. Poorly controlled hypertension (systolic blood pressure & GT; 160 mmHg ordiastolic blood pressure & GT; 100 mmHg);

22. A history of serious cardiovascular and cerebrovascular diseases, including butnot limited to:

23. Severe cardiac rhythm or conduction abnormalities, such as ventriculararrhythmias requiring clinical intervention, degree ⅲ atrioventricular block,etc.;

24. At rest, the QT interval was prolonged (QTc > 450 msec in men or QTc > 470 msecin women).

25. Acute coronary syndrome, congestive heart failure, aortic dissection, stroke,or other grade 3 or higher cardiovascular and cerebrovascular events occurredwithin 6 months before the first dose;

26. The presence of New York Heart Association (NYHA) heart failure grade II orhigher;

27. Patients with a history of allergy to recombinant humanized antibodies or toany excipient component of GNC-038;

28. Women who are pregnant or breastfeeding;

29. Patients with central nervous system invasion;

30. Patients who underwent major surgery within 28 days before the administrationof the drug in this study, or who were to undergo major surgery during thestudy period (except for puncture or lymph node biopsy);

31. Previous recipients of organ transplantation or allogeneic hematopoietic stemcell transplantation (allo-HSCT);

32. Autologous hematopoietic stem cell transplantation (Auto-HSCT) was performedwithin 12 weeks before starting GNC-038 treatment.