Phase I Clinical Trial in Chinese Patients of Advanced and (or) Recurrent Solid Tumor/Lymphoma

Study Overview
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Brief Summary
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With open, single/ multiple dosing and dose escalation, phase I clinical trial scheme to evaluate safety, tolerance and pharmacokinetic properties of Genolimzumab injection in Chinese patients of advanced and (or) recurrent solid tumor/lymphoma

Detailed Description
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Recombinant Programmed death-1(PD-1) humanized monoclonal antibody injection (company code: GB226) is joint developed by Genor Biopharma Co. Ltd and Crown Bioscience,Inc., it is the reorganization of deoxyribonucleic acid (DNA) technology in the Chinese hamster ovary (CHO) cells express system expressed in a immunoglobulin G4 (IgG4) kappa type single resistance to predominate. GB226 had the different new amino acid sequence and molecular structure compared with two marketed PD-1 monoclonal antibody injection and got the approval of China Food and Drug Administration (CFDA) for clinical trial.Pharmaceutical research indicated GB226 cell strain had security source, production process is stable, quality can control, preparation stability, has good compatibility with packaging materials, it has the condition of industrialization, can prepare investigational medicinal product with safety, effective, and controlled quality for clinical research.Pharmacodynamics study show the targets and mechanisms of GB226 is clear, tumor suppression effect is obvious.Toxicology studies show this product in high doses with low toxic, and the toxic is reversible, the most common toxicity is specific to the drug action mechanism.

Official Title
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With Open, Single/Multiple Dosing and Dose Escalation, Phase I Clinical Trial Scheme to Evaluate Safety, Tolerance and Pharmacokinetic Properties of Genolimzumab Injection

Conditions
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Recurrent Lymphocyte Depleted Classical Hodgkin Lymphoma, Advanced Solid Tumor, Recurrent Solid Tumor, Lymphoma

Intervention / Treatment
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* Biological: Geptanolimab Injection 1mg/kg
* Biological: Geptanolimab Injection 3mg/kg
* Biological: Geptanolimab Injection 10mg/kg
* Biological: Geptanolimab Injection 1mg/kg, q2w*6
* Biological: Geptanolimab Injection 3mg/kg, q2w*6
* Biological: Geptanolimab Injection 10mg/kg, , q2w*6
* Biological: Geptanolimab Injection 280mg, q3w
* Biological: Geptanolimab Injection 3mg/kg, q2w


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1. Age: 18-65. Unisex. 2. Understand trial procedure and content and sign informed consent voluntarily; 3. Patients of advanced (phase Ⅲb, multidisciplinary treatment is not appropriate), metastatic (phase IV) or recurrent solid tumor (including melanoma, NSCLC, renal cell carcinoma, head & neck cancer, esophagus cancer, liver cancer, bladder cancer, spongioblastoma) or lymphoma (classical hodgkin lymphoma and (or) peripheral T-cell lymphoma, natural killer (NK)-T cell lymphoma and mediastinal B cell lymphoma) conformed by histology or cytology and cannot be cured by surgery. There is no effective standard treatment now. 4. Agree to provide recorded tumor tissue sample or fresh tissue sample. 5. Eastern Cooperative Oncology Group (ECOG): 0-1; 6. Expected life ≥ 3 months; 7. With at least one measurable and evaluable tumor (solid tumor is subject to criteria for evaluating efficacy of Immune-Related Response Criteria (irRC)/RECIST and lymphoma is subject to criteria/revised criteria of international working group); 8. Chemotherapy of the whole body is completed at least 4 weeks before inclusion. 9. Radiotherapy of the whole body and partial palliative radiotherapy are completed at least 4 weeks before inclusion. 10. Corticosteroids (prednisone>10mg/d or equivalent) has been stopped at least 2 weeks before inclusion. 11. Autotransplantation is completed at least 3 months before inclusion. 12. Major surgeries with the need of general anesthesia are completed at least 4 weeks. Surgeries with the need of local anesthesia/epidural anesthesia are completed at least 2 weeks and the subjects have recovered. Skin biopsies with the need of local anesthesia are completed at least 1 hour before inclusion. 13. Previous tumor biotherapy (tumor vaccine, cell factor or growth factor for the purpose of tumor control) is completed at least 4 weeks before inclusion; 14. Without severe haematological, cardiopulmonary, liver and kidney diseases except protopathic. For patients of solid tumor, hemoglobin≥9g/dl, neutrophile granulocyte≥1.5×109/L, blood platelet≥100×1012/L. For patients of hematologic tumor, hemoglobin≥8g/dl, neutrophile granulocyte≥1.0×109/L, blood platelet≥80×1012/L. 15. Serum creatinine≤1.5xUpper Limit Of Normal (ULN) or creatinine clearance rate≥50mL/min and urine protein<2+ in test paper of urine. For patients with urine protein great than or equal to 2+ in test paper of urine, urine shall be collected in 24 hours and urine protein must less than or be equal to 1g. etc. Exclusion Criteria: 1. Active central nervous system metastasis; If central nervous system (CNS) metastasis of patients can be treated and their symptoms of nervous system can recover to the baseline level (excluding residual signs or symptoms related to CNS treatment) for 2 weeks when they are included, they can participate in the research. Cranial CT or MRI scanning shall be made for the patients 30 days before inclusion. 2. Meningeal metastases or meningeal infiltration of tumors; 3. Patients with other malignant tumors (excluding cured cervical carcinoma in situ and skin basal cell carcinoma) shall not participate in the research, unless he/she has been fully relieved at least 2 years without the need of other treatment or other treatment is not needed during the research. 4. With active, known or suspected autoimmune disease. 5. With previous usage of PD-1 antibody, PD-L1 antibody, PD-L2 antibody or cytotoxic T-lymphocyte-associated antigen-4 immunoglobulin (CTLA-4) antibody for treatment (or other antibody for co-stimulation or check point assess of T cells) 6.With severe internal medicine diseases, including severe heart disease, cerebrovascular disease, uncontrolled diabetes, uncontrolled high blood pressure, active peptic ulcer, active bleeding. 7. With active infection. 8. With active tuberculosis infection; with active tuberculosis infection in the past. 9. Positive hepatitis B surface antigen (HBsAg), hepatitis C antibody (HCV-Ab), acquired immunodeficiency syndrome antibody (Anti-HIV) and treponema pallidum antibody (TP-Ab). Positive subjects of HBsAg may not be excluded from patients of liver cancer. 10. Complication with the need of immunosuppressive drug or complication with the need of corticosteroids for whole or partial body in the dosage of immunosuppressive action. etc.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GB226 1mg/kg single-dose<br>Geptanolimab, 1mg/kg, i.v., single-dose | Biological: Geptanolimab Injection 1mg/kg<br>* single-dose:1mg/kg<br>* Other names: Recombinant PD-1 humanized monoclonal antibody injection, Geptanolimab Injection;|
| Experimental: GB226 3 mg/kg single-dose<br>Geptanolimab, 3mg/kg, i.v., single-dose | Biological: Geptanolimab Injection 3mg/kg<br>* single-dose: 3mg/kg<br>* Other names: Recombinant PD-1 humanized monoclonal antibody injection, Geptanolimab Injection;|
| Experimental: GB226 10mg/kg single-dose<br>Geptanolimab 10mg/kg, i.v., single-dose | Biological: Geptanolimab Injection 10mg/kg<br>* single-dose:10mg/kg<br>* Other names: Recombinant PD-1 humanized monoclonal antibody injection, Geptanolimab Injection;|
| Experimental: GB226 1mg/kg multiple dosing, every 2 weeks<br>Geptanolimab, 1mg/kg, i.v., q2w*6 | Biological: Geptanolimab Injection 1mg/kg, q2w*6<br>* multiple dosing: 1mg/kg, q2w*6<br>* Other names: Recombinant PD-1 humanized monoclonal antibody injection, Geptanolimab Injection;|
| Experimental: GB226 3mg/kg multiple dosing,every 2 weeks<br>Geptanolimab, 3mg/kg, i.v., q2w*6 | Biological: Geptanolimab Injection 3mg/kg, q2w*6<br>* multiple dosing: 3mg/kg, q2w*6<br>* Other names: Recombinant PD-1 humanized monoclonal antibody injection, Geptanolimab Injection;|
| Experimental: GB226 10mg/kg multiple dosing, every 2 weeks<br>Geptanolimab,10mg/kg, i.v., q2w*6 | Biological: Geptanolimab Injection 10mg/kg, , q2w*6<br>* multiple dosing: 10mg/kg, , q2w*6<br>* Other names: Recombinant PD-1 humanized monoclonal antibody injection, Geptanolimab Injection;|
| Experimental: GB226 280mg multiple dosing<br>Geptanolimab, 280mg, i.v., q3w | Biological: Geptanolimab Injection 280mg, q3w<br>* multiple dosing: 280mg, q3w<br>* Other names: Recombinant PD-1 humanized monoclonal antibody injection, Geptanolimab Injection;|
| Experimental: GB226 3mg/kg multiple dosing<br>Geptanolimab, 3mg/kg, i.v., q2w | Biological: Geptanolimab Injection 3mg/kg, q2w<br>* multiple dosing: 3mg/kg, q2w<br>* Other names: Recombinant PD-1 humanized monoclonal antibody injection, Geptanolimab Injection;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| adverse event | adverse event | all adverse events will be recorded from the time the consent form is signed through 30 days following cessation of treatment. | 
| Serious Adverse Event | Serious Adverse Event | all serious adverse events will be recorded from the time the consent form is signed through 30 days following cessation of treatment. | 
| Dose limiting Toxicity, DLT | Dose limiting Toxicity, DLT | Day 1 to Day 28 after first dose | 
| Maximum Tolerated Dose, MTD | Maximum Tolerated Dose, MTD | Day 1 to Day 28 after first dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC 0-t | AUC 0-t | up to 12 weeks | 
| C max | C max | up to 12 weeks | 
| AUC 0-∞ | AUC 0-∞ | up to 12 weeks | 
| T max | T max | up to 12 weeks | 
| Vd | Vd | up to 12 weeks | 
| Ke | Ke | up to 12 weeks | 
| t 1/2 | t 1/2 | up to 12 weeks | 
| CL | CL | up to 12 weeks | 
| Anti-drug antibody, ADA | Anti-drug antibody, ADA | up to 12 weeks | 
| IFN-γ concentration | IFN-γ concentration | up to 12 weeks | 
| peripheral blood CD8+PD-1 receptor occupying ratio | peripheral blood CD8+PD-1 receptor occupying ratio | up to 12 weeks |