A Study of GNC-038 Injection in Patients With Relapsed or Refractory NK/ T-cell Lymphoma, AITL, and Other NHL

Overview

To explore the safety and efficacy of GNC-038 in relapsed or refractory NK/T cell lymphoma, vascular immunomother T cell lymphoma, and other relapsed or refractory NHL, and to determine MTD, MAD, DLT, and RP2D of GNC-038, as well as its pharmacokinetic characteristics and immunogenicity.

Description

Phase Ib: To explore the safety and preliminary effectiveness of GNC-038 under the administration mode of "intravenous infusion for 2h to 4h, once a week (IV, QW), 2 weeks as one cycle", and to determine MTD, MAD, DLT and RP2D of GNC-038. The pharmacokinetic characteristics and immunogenicity of GNC-038 will be evaluated. Phase II: To explore the efficacy, safety and tolerability, pharmacokinetic characteristics and immunogenicity of GNC-038.

Eligibility

Inclusion Criteria:

1. Subjects can understand the informed consent, voluntarily participate in and sign the informed consent.
2. No gender restriction.
3. Age: ≥18 and ≤75 years old.
4. Expected survival time ≥3 months.
5. Patients with histologically confirmed NK/T cell lymphoma or vascular immunomother T cell lymphoma.
6. Patients with relapsed/refractory NK/T cell lymphoma (R/R NKTCL) or relapsed/refractory vascular immunomother T cell lymphoma (AITL):
   1. Patients with recurrent or refractory vascular immunomother T cell lymphoma after initial treatment.
   2. Patients with NK/T cell lymphoma need to have received systematic therapy with asparaginase regimen in the past, and have received radiotherapy for single lesion recurrence or refractory treatment.

        Difficult-to-treat definition: i) the curative effect of end-line treatment did not reach
        PR; Or ii) disease progression within 6 months after terminal line treatment.
        7. In the screening period, there were measurable lesions (lymph node lesions with any
        length ≥1.5cm or exodal lesions with any length > 1.0cm, all of which had metabolic
        activity).
        8. Physical status score ECOG ≤2 points. 9. The adverse reactions of previous antitumor
        therapy were restored to CTCAE level 5.0 evaluation ≤ level 1 (except for indicators that
        the researchers considered might be related to the disease, such as anemia, and toxicities
        that the researchers judged to have no safety risk, such as hair loss, grade 2 peripheral
        neurotoxicity, stable hypothyroidism after hormone replacement therapy, etc.).
        10. Organ function level before initial administration meets the following requirements:
        Bone marrow function: without blood transfusion within 7 days prior to screening, without
        G-CSF (without long-acting rising white needle within 2 weeks) and drug correction:
        Absolute neutrophil count (ANC) ≥1.0×109/L (≥0.5×109/L for subjects with bone marrow
        infiltration); Hemoglobin ≥80 g/L (≥70g/L for subjects with bone marrow infiltration);
        Platelet count ≥75×109/L; Liver function: total bilirubin ≤1.5 ULN (Gilbert's syndrome ≤3
        ULN), transaminase (AST/ALT) ≤2.5 ULN (subjects with liver tumor invasive changes ≤5.0 ULN)
        within 7 days before screening without liver protection drugs; Renal function: creatinine
        (Cr) ≤1.5 ULN and creatinine clearance (Ccr) ≥50 ml/min (according to Cockcroft and Gault
        formula); Urine routine /24 hours urine protein quantification: qualitative urine protein
        ≤1+ (if qualitative urine protein ≥2+, 24 hours urine protein < 1g can be included in the
        group); Cardiac function: left ventricular ejection fraction ≥50%; Coagulation function:
        fibrinogen ≥1.5g/L; Activated partial thrombin time (APTT) ≤1.5 ULN; Prothrombin time (PT)
        ≤1.5 ULN.
        11. Fertile female subjects or fertile male subjects with partners must use highly
        effective contraception from 7 days prior to the first dose until 12 weeks after
        termination of treatment. A fertile female subject must have a negative serum/urine
        pregnancy test within 7 days prior to initial dosing.
        12. Subject is able and willing to comply with visits, treatment plans, laboratory tests,
        and other study-related procedures as specified in the study protocol.
        Exclusion Criteria:
          1. According to NCI-CTCAE v5.0, it was defined as ≥ grade 3 pulmonary disease; Patients
             who currently have interstitial lung disease (ILD) (except those who previously had
             interstitial pneumonia and have recovered).
          2. Active infections requiring systemic treatment, such as severe pneumonia, bacteremia,
             sepsis, etc.
          3. Active tuberculosis.
          4. Patients with hemophagocytic syndrome.
          5. Patients with lesions invading pulmonary great vessels.
          6. Active patients with autoimmune diseases, such as: systemic lupus erythematosus,
             systemic treatment of psoriasis, rheumatoid arthritis, inflammatory bowel disease, and
             hashimoto's thyroiditis, etc., with the exception of type I diabetes, only replacement
             therapy can control the hypothyroidism, no systemic treatment of skin disease (e.g.,
             vitiligo, psoriasis), B cells caused by autoimmune disease.
          7. Non-melanoma skin cancer in situ, superficial bladder cancer in situ, cervical cancer
             in situ, gastrointestinal intramucosal cancer, breast cancer, localized prostate
             cancer and other malignant tumors that were combined with other malignant tumors
             within 5 years prior to the first administration of the drug, except those that the
             researchers thought could be included.
          8. HBsAg positive or HBcAb positive, and HBV-DNA detection ≥ detection value lower limit
             (HBV-DNA detection in the normal range and regular use of anti-HBV drugs except
             patients); HCV antibody was positive and HCV-RNA≥ lower limit of detection value.
          9. Poorly controlled hypertension (systolic blood pressure &gt;160 mmHg or diastolic
             blood pressure &gt;100 mmHg).
         10. A history of severe cardiovascular and cerebrovascular diseases, including but not
             limited to:
             Severe cardiac rhythm or conduction abnormalities, such as ventricular arrhythmias and
             degree III atrioventricular block that require clinical intervention; Prolonged QT
             interval at rest (QTc > 450 msec in men or 470 msec in women); Acute coronary
             syndrome, congestive heart failure, aortic dissection, stroke, or other grade 3 or
             higher cardiovascular and cerebrovascular events occurring within 6 months prior to
             initial administration; Present with heart failure ≥II on the New York Heart
             Association (NYHA) cardiac function scale.
         11. Patients with a history of allergy to recombinant humanized antibodies or to any
             excipient component of GNC-038.
         12. Pregnant or breastfeeding women.
         13. Patients with central nervous system invasion.
         14. Patients who received major surgery within 28 days prior to drug administration in
             this study, or planned to undergo major surgery during the study period (except for
             procedures such as puncture or lymph node biopsy).
         15. Previous recipients of organ transplantation or allogeneic hematopoietic stem cell
             transplantation (Allo-HSCT).
         16. Autologous hematopoietic stem cell transplantation (Auto-HSCT) within 24 weeks before
             starting GNC-038 therapy.
         17. Immunosuppressants are being used, including, but not limited to, cyclosporine,
             tacrolimus, etc. within 2 weeks prior to treatment with GNC-038.
         18. Radiotherapy was received within 4 weeks prior to the initiation of GNC-038 therapy.
         19. Received chemotherapy and small molecule targeted therapy within 2 weeks prior to
             treatment.
         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 of
             this trial.
         22. A history of immunodeficiency, including HIV positive testing, or other acquired,
             congenital immunodeficiency diseases.
         23. Other conditions deemed unsuitable for participation in this clinical trial by the
             investigator.