Phase I Clinical Study of GNC-038 in Patients With Non-Hodgkin's Lymphoma or Acute Lymphoblastic Leukemia

Inclusion Criteria:

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

2. No gender limit.

3. Age: ≥18 years old.

4. Expected survival time ≥ 3 months.

5. Histologically or cytologically confirmed non-Hodgkin's lymphoma or acutelymphoblastic leukemia.

6. Patients with relapsed refractory non-Hodgkin lymphoma (R/R NHL). Specifically,patients who relapsed for the first time and still progressed during second-linetreatment; Patients with relapse after second-line or multiline therapy; Refractorypatients showed no remission or progress after full dose and full cycle use ofstandard or current clinically commonly selected combination therapy regimen, and noremission or progress after replacement of second-line regimen; Patients withrelapsed or refractory non-Hodgkin lymphoma who were determined to have no or noother treatments available/intolerant.

7. Relapsed or refractory acute lymphoblastic leukemia (R/R ALL), including: noresponse after more than 6 weeks of induction chemotherapy, or no response after 2cycles of induction chemotherapy; A second or more recurrence of bone marrow; Orrelapse for the first time after chemotherapy with no remission after at least 1cycle of salvage therapy; Bone marrow recurrence after autologous stem celltransplantation (auto-HSCT); Patients with relapsed or refractory acutelymphoblastic leukemia were determined to have no or no other treatments/intolerant.

8. Patients with Philadelphia chromosome positive (Ph+) ALL who are intolerant to orfail to treat 1 and/or 2 generation tyrosine kinase inhibitors (TKI), or Ph+ALL whohave a T315I mutation, do not require TKI salvage therapy.

9. For patients with NHL, there were measurable lesions in the screening period (lymphnode lesions with any length ≥1.5cm or exodal lesions with any length > 1.0cm);CLL/SLL: peripheral blood leukemia cells ≥5.0×109/L; Or lymph node lesions of anylength ≥1.5cm; WM: IgM> 2 x ULN.

10. For AITL and NK/T lymphoma, a membrane CD3 negative test is required.

11. Physical status score ECOG ≤2 points.

12. The toxicity of previous antitumor therapy has returned to ≤ Class 1 as defined byNCI-CTCAE v5.0 (except for toxicities that the investigators judged to be of nosafety risk, such as alopecia, grade 2 peripheral neurotoxicity, and stablehypothyroidism after hormone replacement therapy).

13. The organ function level meets the following requirements: Bone marrow function (forNHL patients only) : without blood transfusion within 7 days prior to screening,without G-CSF (without long-acting rising white needle within 2 weeks), and withoutdrug correction: Absolute neutrophil count (ANC) ≥1.0×109/L (≥0.5×109/L for subjectswith bone marrow infiltration); Hemoglobin ≥80 g/L (≥70g/L for subjects with bonemarrow infiltration); Platelet count ≥50×109/L; Liver function: Total bilirubin ≤1.5ULN (Gilbert's syndrome ≤3 ULN), transaminase (AST/ALT) ≤2.5ULN (in subjects withtumor invasive changes in the liver ≤5.0 ULN), and/or alkaline phosphatase ≤5 ULNwhen not corrected with hepatoprotective drugs within 7 days prior to screening;Renal function: creatinine (Cr) ≤1.5 ULN and creatinine clearance (Ccr) ≥50 ml/min (based on the center's calculation criteria). The investigators judged renalfunction intact without injury, except that abnormal creatinine index was caused bytumor. Coagulation function: fibrinogen ≥1.5g/L; Activated partial thromboplastintime (APTT) ≤1.5×ULN; Prothrombin time (PT) ≤1.5×ULN.

14. Fertile female subjects or male subjects with fertile partners must use highlyeffective contraception from 7 days before the first dose until 6 months after thelast dose. A fertile female subject must have a negative serum pregnancy test within 7 days prior to initial dosing.

15. The subject is able and willing to comply with visits, treatment plans, laboratorytests, and other study-related procedures as specified in the study protocol.

Exclusion Criteria:

1. Live virus vaccine (including attenuated live vaccine) was administered within 28days prior to administration in this study.

2. Patients who received major surgery within 28 days prior to administration of thedrug or planned to undergo major surgery during the study period (except forprocedures such as puncture or lymph node biopsy).

3. Defined as ≥ Grade 3 pulmonary diseases according to NCI-CTCAE v5.0; Patients withpresent or history of interstitial lung disease (ILD).

4. Systemic serious infections occurred within 1 week before screening, including butnot limited to severe pneumonia caused by fungi, bacteria and viruses, bacteremia orserious infectious complications.

5. Active tuberculosis.

6. People with active autoimmune disease, or a history of autoimmune disease, Includingbut not limited to Crohn's disease, ulcerative colitis, systemic lupuserythematosus, sarcoidosis, Wegener syndrome, polyvasculitis granulomatosis,autoimmune hepatitis, systemic sclerosing disease, autoimmune vasculitis, autoimmuneneuropathy (Guillain-Barre syndrome), etc. Exceptions include type I diabetes,hypothyroidism stable on hormone replacement therapy (including hypothyroidismcaused by autoimmune thyroid disease), psoriasis or vitiligo that does not requiresystemic therapy, and B-cell autoimmune disease.

7. Non-melanoma skin cancer in situ, superficial bladder cancer in situ, cervicalcancer in situ, gastrointestinal intramucosal cancer, breast cancer, localizedprostate cancer and other malignant tumors that were combined with other malignanttumors within 5 years prior to the first administration of the drug, and those thathad been cured and had not recurred within 5 years were excluded.

8. HBsAg positive; HBcAb positive and HBV-DNA detection ≥ lower limit of detectionvalue; HCV antibody positive and HCV-RNA≥ lower limit of detection value; HIVantibody positive.

9. Poorly controlled hypertension (systolic blood pressure > 150 mmHg or diastolicblood pressure > 100 mmHg).

10. A history of severe cardiovascular and cerebrovascular diseases, including but notlimited to: severe cardiac rhythm or conduction abnormalities, such as ventriculararrhythmia requiring clinical intervention, degree III atrioventricular block, etc.;At rest, the QT interval was prolonged (QTc > 450 msec in men or 470msec in women);Acute coronary syndrome, congestive heart failure, aortic dissection, stroke, orother grade 3 or higher cardiovascular and cerebrovascular events occurred within 6months prior to initial administration; There is heart failure ≥II on the New YorkHeart Association (NYHA) cardiac function scale.

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

12. Pregnant or breastfeeding women.

13. Patients with central nervous system invasion.

14. Previous recipients of organ transplantation or allogeneic hematopoietic stem celltransplantation (Allo-HSCT).

15. Autologous hematopoietic stem cell transplantation (AutoHSCT) was performed within 12 weeks prior to initiation of GNC-038 therapy.

16. Immunosuppressants are being used, including but not limited to: cyclosporine,tacrolimus, etc., within 2 weeks prior to treatment with GNC-038; GNC-038 receivedhigh doses of glucocorticoids within 2 weeks prior to treatment (longer than 14days, daily steady dose > 30mg of prednisone or equal doses of othercorticosteroids), except for patients with R/R ALL, Dexamethasone should besymptomatic when R/R ALL patients have more than 50% bone marrow protocells orperipheral protocells ≥15000/μL during the screening period (see 4.6.2 Availabilityof drugs during the trial).

17. Received radiotherapy within 4 weeks prior to initiation of GNC-038 treatment.

18. Patients with NHL who had received anti-CD20 or anti-CD79B therapy within 4 weeksbefore starting GNC-038 therapy continued to respond; ALL patients were treated withTKI, anti-CD19 or anti-CD22 within 4 weeks prior to GNC-038 and still responded, andwere treated with bonatumab (CD19×CD3) and izumab - oxomicin (CD22-ADC) within 4weeks prior to treatment.

19. Received chemotherapy and small-molecule targeted therapy within 2 weeks prior totreatment.

20. Received CAR T therapy within 12 weeks prior to initiation of GNC-038 therapy.

21. Participants in any other clinical trial within 4 weeks prior to administration ofthis trial.

22. Other conditions deemed unsuitable for participation in this clinical trial by theinvestigator.