A Study of GNC-035 in Relapsed or Refractory Chronic Lymphocytic Leukemia and Other Hematological Malignancies

Inclusion Criteria:

1. Subjects can understand the informed consent form, voluntarily participate in andsign the informed consent form;

2. No gender limit;

3. Age: ≥18 years old (≤75 years old for climbing);

4. expected survival time ≥3 months;

5. Patients with hematological malignancies such as relapsed/refractory chroniclymphocytic leukemia confirmed by histology or cytology;

6. For relapsed or refractory chronic lymphocytic leukemia (CLL/SLL), specifically: Patients who have relapsed after at least one line of standard therapy or have noresponse to or intolerance to standard regimens; Patients with relapsed orrefractory chronic lymphocytic leukemia who were not or were ineligiblefor/intolerant of other therapies according to investigator assessment. Relapsed and refractory were defined as follows: Relapse was defined as disease progression after a response to adequate treatment,including at least one regimen containing a BTK inhibitor. Refractory was defined as refractory to BTK inhibitor, failure to achieve remissionafter adequate treatment with BTK inhibitor-containing regimens (combination therapyor monotherapy), or disease progression during treatment or within 6 months aftercompletion of adequate treatment.

7. For other patients with relapsed refractory non-Hodgkin lymphoma. These include: Patients who experience failure of at least two lines of therapy; Relapsed orrefractory patients who are not or are ineligible for/intolerant of other therapiesas judged by the investigator. Relapsed and refractory were defined as follows: Relapse was defined as disease progression after a response to adequate treatment,including at least one anti-CD20 monoclonal antibody. Refractory was defined as refractory to anti-CD20 monoclonal antibody, failure toachieve remission after adequate treatment with anti-CD20 monoclonal antibody (combination therapy or monotherapy), or disease progression during treatment or 6months after completion of adequate treatment. Among them, "adequate treatment with anti-CD20 monoclonal antibody" refers to thecompletion of full cycle of anti-CD20 monoclonal antibody combined with chemotherapyaccording to pathological type and disease stage, or anti-CD20 monoclonal antibodymonotherapy at a dose of 375 mg/m2 once a week for at least 4 injections.Progression during treatment required the completion of at least one cycle ofanti-CD20 monoclonal antibody combined with chemotherapy or monotherapy ifprogression occurred during induction therapy. At least one dose was completed ifprogression occurred during maintenance therapy. "Response" included complete andpartial responses.

8. CLL/SLL: peripheral blood leukemia cells ≥5.0×109/L; Or the long diameter of anylymph node lesion ≥1.5cm; Patients with non-Hodgkin's lymphoma had measurabledisease at screening (nodal disease ≥1.5cm in the greatest dimension or extranodaldisease > 1.0cm in the greatest dimension).

9. ECOG ≤2;

10. Toxicity of previous antineoplastic therapy has returned to ≤ grade 1 defined byNCI-CTCAE v5.0 (except alopecia);

11. Organ function within 7 days before the first dose: Bone marrow function (for patients with non-Hodgkin lymphoma only) : without bloodtransfusion, G-CSF (for 2 weeks), and medication correction within 7 days prior toscreening; Absolute neutrophil count (ANC) ≥1.0×109/L (≥0.5×109/L if the subject hasbone marrow infiltration); Hemoglobin ≥80 g/L (≥70g/L if the subject has bone marrowinfiltration); Platelet count ≥75×109/L; Liver function: total bilirubin, ≤1.5 ULN (Gilbert's syndrome, ≤3 ULN), and aminotransferase (AST/ALT), ≤2.5 ULN (for thosewith liver tumor invasive changes, ≤5.0 ULN) without correction withhepatoprotective medication within 7 days before screening examination; Renalfunction: creatinine (Cr) ≤1.5 ULN or creatinine clearance (Ccr) ≥60 mL/ minute (based on center calculation criteria) Coagulation: activated partial thromboplastintime (APTT) ≤1.5×ULN Prothrombin time (PT) ≤1.5×ULN.

12. Female subjects of childbearing potential or male subjects with a fertile partnermust use highly effective contraception from 7 days before the first dose until 12weeks after the last dose. Female subjects of childbearing potential must have anegative serum/urine pregnancy test within 7 days before the first dose;

13. Participants were able and willing to comply with protocol-specified visits,treatment plans, laboratory tests, and other study-related procedures.

Exclusion Criteria:

1. Patients who underwent major surgery within 28 days before study administration orwho were scheduled to undergo major surgery during the study (" major surgery "wasdefined by the investigator);

2. Pulmonary disease grade ≥3 according to NCI-CTCAE v5.0, including dyspnea at rest orrequiring continuous oxygen therapy; Patients with current interstitial lung disease (ILD) (except those who have recovered from previous interstitial pneumonia);

3. Severe systemic infection occurred within 4 weeks before screening, including butnot limited to severe pneumonia caused by fungi, bacteria, or viruses, bacteremia,or serious infectious complications;

4. Patients with active autoimmune disease or a history of autoimmune disease. Patientswith type I diabetes mellitus, hypothyroidism that is stable withhormone-replacement therapy (including hypothyroidism due to autoimmune thyroiddisease), psoriasis, or vitiligo that does not require systemic therapy, as deemedby the investigators, were excluded.

5. Patients with other malignant tumors within 3 years before the first drugadministration, cured non-melanoma skin cancer in situ, superficial bladder cancer,cervical cancer in situ, gastrointestinal mucosal cancer, breast cancer, localizedprostate cancer, and other patients without recurrence within 3 years were excluded.

6. Human immunodeficiency virus antibody (HIVAb) positive, active tuberculosis, activehepatitis B virus infection (HBsAg positive or HBcAb positive and HBV-DNA test ≥central detection lower limit) or hepatitis C virus infection (HCV antibody positiveand HCV-RNA≥ central detection lower limit);

7. Hypertension poorly controlled by medication (systolic blood pressure > 150 mmHgor diastolic blood pressure > 100 mmHg);

8. Left ventricular ejection fraction ≤45%, or history of major heart disease within 1year:

9. New York Heart Association (NYHA) class III or IV congestive heart failure;

10. Acute coronary syndrome, myocardial infarction or bypass or stent surgery (except those judged by the investigator to be stable);

11. Patients with unstable angina pectoris;

12. QT prolongation (QTcf > 450 msec in men or > 470 msec in women), complete leftbundle branch block, degree III atrioventricular block, and arrhythmiarequiring medical intervention;

13. Other cardiac conditions deemed by the investigator to be ineligible forenrollment.

14. Patients with a history of allergy to recombinant humanized antibodies or to any ofthe excipients of GNC-035;

15. Women who are pregnant or breastfeeding;

16. Presence of central nervous system invasion;

17. Prior organ transplantation or allogeneic hematopoietic stem cell transplantation (ALLo-HSCT);

18. Autologous hematopoietic stem cell transplantation (Auto-HSCT) within 12 weeksbefore starting GNC-035 therapy;

19. Current use of immunosuppressive agents, including, but not limited to,cyclosporine, tacrolimus, etc., within 2 weeks or 5 half-life periods prior toGNC-035 treatment, whichever is shorter;

20. Received radiotherapy, macromolecular targeted drugs within 4 weeks before GNC-035treatment; Chemotherapy and a small-molecule targeted agent were administered 2weeks or within five half-lives before treatment, whichever was less.

21. Received anti-CD20 therapy within 4 weeks prior to GNC-035 therapy and isresponding;

22. Received CAR-T therapy within 12 weeks before GNC-035 treatment;

23. Use of a study drug from another clinical trial within 4 weeks or 5 half-lives,whichever was shorter, before the trial dose;

24. Other circumstances that the investigator deemed inappropriate for participation inthe trial.