Clinical Trials /

A Study of GNC-038, a Tetra-specific Antibody, in Participants With R/R Non-Hodgkin Lymphoma

NCT04606433

Description:

In this study, the safety and tolerability of GNC-038 in participants with recurrent or refractory Non-Hodgkin lymphoma will be investigated to assess the dose-limiting toxicity (DLT), maximum tolerated dose (MTD) or maximum administered dose (MAD) for MTD is not reached of GNC-038. The recommended dose for future clinical study will also be determined.

Related Conditions:
  • Non-Hodgkin Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Study of GNC-038, a Tetra-specific Antibody, in Participants With R/R Non-Hodgkin Lymphoma
  • Official Title: An Open-Label, Multi-Center, Phase Ia Study to Evaluate the Safety, Tolerability and Pharmacokinetic Characteristics of Tetra-specific Antibody GNC-038 in Participants With Recurrent or Refractory Non-Hodgkin Lymphoma

Clinical Trial IDs

  • ORG STUDY ID: GNC-038-101
  • NCT ID: NCT04606433

Conditions

  • Non-hodgkin Lymphoma

Interventions

DrugSynonymsArms
GNC-038Study treatment

Purpose

In this study, the safety and tolerability of GNC-038 in participants with recurrent or refractory Non-Hodgkin lymphoma will be investigated to assess the dose-limiting toxicity (DLT), maximum tolerated dose (MTD) or maximum administered dose (MAD) for MTD is not reached of GNC-038. The recommended dose for future clinical study will also be determined.

Trial Arms

NameTypeDescriptionInterventions
Study treatmentExperimentalPatients receive GNC-038 as intravenous infusion for one cycle. Participants with no intolerable AEs could continue for another three cycles. Participants with a clinical benefit after four cycles' treatment could also receive additional treatment for another four cycles at the same dose level.
  • GNC-038

Eligibility Criteria

        Inclusion Criteria:

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

          2. No gender limit;

          3. Age: ≥18 years old

          4. Expected survival time ≥ 3 months.

          5. Has suffered from Non-Hodgkin lymphoma confirmed by histology or cytology.

          6. Those who have recurrent or refractory Non-Hodgkin lymphoma, including:

               -  Participants with first recurrence and progress during second-line treatment;

               -  Participants with recurrence after second-line or multi-line treatment;

               -  Refractory participants referred to those with no remission or progression after
                  full dose and full cycle use of standard or current clinically commonly selected
                  combination treatment regimens, and those with no remission or progression after
                  replacement of second-line regimens;

               -  Recurrent or refractory participants that are, determined by the investigators,
                  not applicable/tolerated to other treatments.

          7. For non-Hodgkin's lymphoma, there are measurable lesions during the screening period
             (any long diameter of lymph node lesions ≥ 1.5 cm or any long diameter of extra-nodal
             lesions greater than 1.0 cm); CLL/SLL: peripheral blood leukemia cells ≥5.0×109/L; One
             length diameter of lymph node lesions ≥1.5cm; WM: IgM﹥2×ULN.

          8. Physical fitness score ECOG≤2 points.

          9. The toxicity of the previous anti-tumor therapy has been restored to the level ≤1
             defined by NCI-CTCAE v5.0 (except for hair loss).

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

               -  Bone marrow function: In the case of no blood transfusion, no use of G-CSF (no
                  use 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); Platelet count ≥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 in
                  participants with Gilbert's syndrome), transaminase (AST/ALT) ≤ 2.5 ULN
                  (participants with tumor infiltration in the liver ≤5.0 ULN), and/or alkaline
                  phosphatase (AP) ≤5 ULN.

               -  Kidney function: creatinine (Cr) ≤ 1.5 ULN and creatinine clearance (Ccr) ≥ 50
                  mL/min (calculated by the research center).

               -  Coagulation function: fibrinogen (FIB) ≥1.0g/L; activated partial thromboplastin
                  time (APTT) ≤1.5×ULN; prothrombin time (PT) ≤1.5×ULN.

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

        Exclusion Criteria:

          1. Has received live virus vaccines (including live attenuated vaccines) within 28 days
             prior to GNC-038 treatment.

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

          3. Has grade 3 or above lung disease defined according to NCI-CTCAE v5.0, including
             resting dyspnea, or requiring continuous oxygen therapy, or a history of interstitial
             lung disease (ILD).

          4. Severe systemic infections occurred within 4 weeks prior to screening, including but
             not limited to severe pneumonia, bacteremia, or severe infection complications caused
             by fungi, bacteria, and viruses.

          5. Participants at risk of active autoimmune diseases, or with a history of autoimmune
             diseases, including but not limited to Crohn's disease, ulcerative colitis, systemic
             lupus erythematosus, sarcoidosis, Wegener syndrome (polyangiitis granuloma Disease,
             Graves' disease, rheumatoid arthritis, pituitary inflammation, uveitis), autoimmune
             hepatitis, systemic sclerosis, Hashimoto' s thyroiditis, autoimmune vasculitis,
             autoimmune neuropathy (Guillain-Barré syndrome), etc. Except for the following
             conditions: Type I diabetes, hormone replacement therapy for stable hypothyroidism
             (including hypothyroidism caused by autoimmune thyroid disease), psoriasis or vitiligo
             that does not require systemic treatment.

          6. Complicated with other malignant tumors within 5 years prior to GNC-038 treatment,
             except for cured skin squamous cell carcinoma, basal cell carcinoma, superficial
             bladder cancer, prostate/cervix/breast carcinoma in situ (only phase Ib).

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

          8. Participants with poorly controlled hypertension by antihypertensive drugs (systolic
             blood pressure>150 mmHg or diastolic blood pressure>100 mmHg).

          9. Left ventricular ejection fraction ≤45%, (hypersensitivity) troponin>ULN.

         10. History of severe heart disease:

               -  New York Heart Association (NYHA) grade III or IV congestive heart failure;

               -  Have had myocardial infarction, bypass or stent surgery within 6 months prior to
                  administration;

               -  Other heart diseases that the investigator judges are not suitable for including
                  in the group.

         11. Participants with prolonged QT interval (male QTc> 450 msec or female QTc> 470 msec),
             complete left bundle branch block, III grade atrioventricular block.

         12. Has a history of allergies to recombinant humanized antibodies or human-mouse chimeric
             antibodies or any of the components of SI-B003.

         13. Pregnant or breastfeeding women.

         14. Other conditions that the investigator believes that it is not suitable for
             participating in this clinical trial.

         15. Has suffered from or accompanied by central nervous system diseases, including but not
             limited to: epilepsy, paralysis, stroke, severe brain injury, Alzheimer's, Parkinson's
             disease, cerebellar disease, cerebral organic syndrome, and psychosis.

         16. There is an invasion of the central nervous system.

         17. Has accepted organ transplantation or allogeneic hematopoietic stem cell
             transplantation (ALLo-HSCT).

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

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

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

         21. Has received anti-CD20 or anti-CD79b treatment within 4 weeks prior to GNC-038
             treatment, and has received chemotherapy, small molecule targeted drugs and anti-tumor
             traditional Chinese medicine within 2 weeks prior to GNC-038 treatment.

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

         23. Has participated in any other clinical trials within 4 weeks prior to GNC-038
             treatment.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Dose limiting toxicity (DLT)
Time Frame:Up to 14 days after the first dose of GNC-038
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Adverse Events of special interest (AESI)
Time Frame:Up to approximately 24 months
Safety Issue:
Description:
Measure:Cmax: Maximum serum concentration of GNC-038
Time Frame:Up to 14 days after the first dose of GNC-038
Safety Issue:
Description:
Measure:Css: Concentration of GNC-038 at steady state plateau
Time Frame:Up to 14 days after the first dose of GNC-038
Safety Issue:
Description:
Measure:Tmax: Time to maximum serum concentration (Tmax) of GNC-038
Time Frame:Up to 14 days after the first dose of GNC-038
Safety Issue:
Description:
Measure:T1/2: Half-life of GNC-038
Time Frame:Up to 14 days after the first dose of GNC-038
Safety Issue:
Description:
Measure:AUC0-inf: Area under the serum concentration-time curve from time 0 to infinity
Time Frame:Up to 14 days after the first dose of GNC-038
Safety Issue:
Description:
Measure:AUC0-t: Area under the serum concentration-time curve from time 0 to the time of the last measurable concentration
Time Frame:Up to 14 days after the first dose of GNC-038
Safety Issue:
Description:
Measure:CL: Clearance in the serum of SI-B001 per unit of time
Time Frame:Up to 14 days after the first dose of GNC-038
Safety Issue:
Description:
Measure:ADA (Anti-drug antibody)
Time Frame:Up to approximately 24 months
Safety Issue:
Description:
Measure:Nab (Neutralizing antibody)
Time Frame:Up to approximately 24 months
Safety Issue:
Description:
Measure:ORR (Objective Response Rate )
Time Frame:Up to approximately 24 months
Safety Issue:
Description:
Measure:DCR (Disease Control Rate)
Time Frame:Up to approximately 24 months
Safety Issue:
Description:
Measure:PFS (Progression-free Survival)
Time Frame:Up to approximately 24 months
Safety Issue:
Description:
Measure:DOR (Duration of Response)
Time Frame:Up to approximately 24 months
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Sichuan Baili Pharmaceutical Co., Ltd.

Trial Keywords

  • NHL

Last Updated

October 23, 2020