Phase I Clinical Trial in Chinese Patients of Advanced and (or) Recurrent Solid Tumor/Lymphoma (GB226)

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

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

Study Overview

• Status: Recruiting
• Conditions: Lymphoma; Advanced Solid Tumor; Recurrent Solid Tumor; Recurrent Lymphocyte Depleted Classical Hodgkin Lymphoma
• Intervention / Treatment: 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

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 72
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100021
      • Not yet recruiting
      • Cancer Hospital Chinese Academy of Medical Sciences
  • Heilongjiang
    • Harbin, Heilongjiang, China, 150081
      • Recruiting
      • Harbin Medical University Cancer Hospital
      • Principal Investigator: Qingyuan Zhang, Doctor
      • Contact: Qingyuan Zhang, Doctor

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

8

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Genor Biopharma Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): October 19, 2017
• Primary Completion (Anticipated): June 1, 2022
• Study Completion (Anticipated): August 1, 2022

Study Registration Dates

• First Submitted: December 6, 2017
• First Submitted That Met QC Criteria: December 11, 2017
• First Posted (Actual): December 14, 2017

Study Record Updates

• Last Update Posted (Actual): August 16, 2021
• Last Update Submitted That Met QC Criteria: August 12, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Immune System Diseases; Neoplasms by Histologic Type; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Disease Attributes; Neoplasms; Lymphoma; Recurrence; Physiological Effects of Drugs; Antineoplastic Agents; Immunologic Factors; Antibodies; Immunoglobulins; Antibodies, Monoclonal; Antineoplastic Agents, Immunological
• Other Study ID Numbers: Gxplore-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: There is not a plan to make individual participant data available.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No