Phase Ⅰ Study to Evaluate the Safety and Tolerability of Using F520

NCT03657381 | Unknown Phase 1

• 1 other identifier: NTP-F520-001
• Study Type: interventional
• Target: 75
• Locations: 1 country
• Sites: 1

Brief Summary

Recombinant Programmed death-1(PD-1) humanized monoclonal antibody injection (company code: F520) is joint developed by Shandong New Time Pharmaceutical Co., LTD., it is the reorganization of deoxyribonucleic acid (DNA) technology in the Chinese hamster ovary (CHO) cells express system expressed in a immunoglobulin G1 (IgG1) kappa type single resistance to predominate. F520 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 F520 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 F520is 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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Number of participants with treatment-related adverse events as assessed by CTCAE v4.0.

  1.5 years

Secondary Outcomes (13)

• PD-1 receptor occupancy of blood

  3 years

• Objective Response Rate (ORR) by irRC/ RECIST 1.1/RANO/cheson2007

  3 years

• Disease Control Rate (DCR) by irRC/ RECIST 1.1/RANO/cheson2007

  3 years

• Maximum Plasma Concentration (Cmax) after single dose injection of Anti-PD-1 Monoclonal Antibody (mAb)

  1.5years

• Peak Time (Tmax) after single dose injection of Anti-PD-1 mAb

  1.5years

Other Outcomes (1)

• correlation analysis of Tumor marker and therapeutic effect

  3 years

Study Arms (11)

F520 0.2mg/kg single-dose

EXPERIMENTAL

F520 0.2mg/kg single-dose

Drug: Recombinant Humanized Anti-PD-1 Monoclonal Antibody Injection

F520 1.0mg/kg single-dose

EXPERIMENTAL

F520 1.0mg/kg single-dose

Drug: Recombinant Humanized Anti-PD-1 Monoclonal Antibody Injection

F520 3.0mg/kg single-dose

EXPERIMENTAL

F520 3.0mg/kg single-dose

Drug: Recombinant Humanized Anti-PD-1 Monoclonal Antibody Injection

F520 200mg/times single-dose

EXPERIMENTAL

F520 200mg/times single-dose

Drug: Recombinant Humanized Anti-PD-1 Monoclonal Antibody Injection

F520 10mg/kg single-dose

EXPERIMENTAL

F520 10mg/kg single-dose

Drug: Recombinant Humanized Anti-PD-1 Monoclonal Antibody Injection

F520 1mg/kg multiple dosing, every 2 weeks

EXPERIMENTAL

F520 1mg/kg every 2 weeks

Drug: Recombinant Humanized Anti-PD-1 Monoclonal Antibody Injection

F520 3mg/kg multiple dosing, every 2 weeks

EXPERIMENTAL

F520 3mg/kg every 2 weeks

Drug: Recombinant Humanized Anti-PD-1 Monoclonal Antibody Injection

F520 200mg/times multiple dosing, every 2 weeks

EXPERIMENTAL

F520 200mg/times every 2 weeks

Drug: Recombinant Humanized Anti-PD-1 Monoclonal Antibody Injection

F520 10mg/kg multiple dosing, every 2 weeks

EXPERIMENTAL

F520 10mg/kg every 2 weeks

Drug: Recombinant Humanized Anti-PD-1 Monoclonal Antibody Injection

F520 3mg/kg multiple dosing, every 3 weeks

EXPERIMENTAL

F520 3mg/kg every 3 weeks

Drug: Recombinant Humanized Anti-PD-1 Monoclonal Antibody Injection

F520 200mg/times multiple dosing, every 3 weeks

EXPERIMENTAL

F520 200mg/times every 3 weeks

Drug: Recombinant Humanized Anti-PD-1 Monoclonal Antibody Injection

Interventions

Recombinant Humanized Anti-PD-1 Monoclonal Antibody Injection DRUG

Biological: F520 single-dose:0.2mg/kg, 1.0mg/kg, 3.0mg/kg, 200mg/times, 10mg/kg; multiple dosing: 1mg/kg, 3mg/kg, 200mg/times, 10mg/kg, treat every 2 weeks; multiple dosing: 3mg/kg, 200mg/times, treat every 3 weeks.

F520 0.2mg/kg single-dose; F520 1.0mg/kg single-dose; F520 10mg/kg multiple dosing, every 2 weeks; F520 10mg/kg single-dose; F520 1mg/kg multiple dosing, every 2 weeks; F520 200mg/times multiple dosing, every 2 weeks; F520 200mg/times multiple dosing, every 3 weeks; F520 200mg/times single-dose; F520 3.0mg/kg single-dose; F520 3mg/kg multiple dosing, every 2 weeks; F520 3mg/kg multiple dosing, every 3 weeks

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female 18-65 years of age;
• Histologically or cell confirmed advanced, unresectable or metastatic disease tumor and failure to standard therapies or lack of standard therapy(disease progress or failed to tolerate the toxicity, such as chemotherapy, targeted therapy, and other immunotherapies other than PD-1/PD-L1);
• Agree to provide archived tumor tissue specimens or fresh tissue specimens;
• ECOG performance status of 0 or 1;
• Life expectancy ≥ 12 weeks.;
• At least one measurable and evaluable tumor lesion (in accordance with international working group criteria/RANO/cheson 2007)；
• Adequate laboratory parameters during the screening period as evidenced by the following（No blood components and cell growth factors are allowed within 28 days prior to screening）:
• routine blood tests: Absolute neutrophil count ≥1.0×109/L ;Platelets ≥100×109/L;Hemoglobin ≥ 9.0 g/dL; Liver function：Total bilirubin (TBIL) ≤1.5×upper limit of normal (ULN), ALT and AST ≤2.5ULN; for subjects with liver metastases, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 5×ULN, Total bilirubin (TBIL) ≤3×upper limit of normal (ULN); Renal function CCr≤1.5×ULN，Creatinine clearance≥50 mL/min;
• Thyroid function indicators: thyroid-stimulating hormone (TSH) and free thyroxine (FT3/FT4) are within the normal range;
• Understand study procedures and contents, and voluntarily sign the written informed consent form.

You may not qualify if:

• Subjects with any active autoimmune disease or history of autoimmune disease, including but not limited to the following: Immune-related neurological diseases, multiple sclerosis, autoimmune (demyelinating) neuropathy, Guillain-Barre syndrome, myasthenia gravis, systemic lupus erythematosus, connective tissue disease, scleroderma, inflammatory bowel disease including Crowe Enthusiasm and ulcerative colitis, autoimmune hepatitis, toxic epidermal necrolysis or Stevens-Johnson syndrome；
• Presence of symptomatic central nervous system (CNS) metastases；
• Concurrent medical condition requiring the use of immunosuppressive medications, or immunosuppressive doses of systemic or absorbable topical corticosteroids. Doses \> 10 mg/day prednisone or equivalent are prohibited within 14 days before entering the group and during the study period;
• Prior radiotherapy, systemic chemotherapy hormone therapy, surgery or target therapy within 4 weeks or 5 half-lives(whichever is longer) before the study drug administration, or any unresolved AEs \> CTC-AE Grade 1;
• Autologous hematopoietic stem cell transplantation (ASCT) has been completed at least 3 months before receiveing first dose;
• Known history of hypersensitivity to macromolecular protein preparation or any components of the F520 formulation；
• Patients receiving any anti-infection vaccine within 4 weeks before enrollment;
• History or concurrent with other malignant disease, except completely cured basal cell skin cancers and carcinoma in situs of cervix;
• Uncontrolled clinically significant heart disease, including but not limited to the following: (1) \>2 NYHA 2 congestive heart failure; (2) unstable angina, (3) myocardial infarction within the past 1 year; (4) clinically significant supraventricular arrhythmia or ventricular arrhythmia requirement for treatment or intervention;
• Active infection（needing therapy） or an unexplained fever \> 38.5°C during screening or before the first scheduled day of dosing (subjects with tumor fever may be enrolled at the discretion of the investigator);
• Patients with active pulmonary tuberculosis; patients who previously had active pulmonary tuberculosis;
• History of immunodeficiency (HIV) or active hepatitis(Hepatitis B: HBsAg, Anti-HBs, HBeAg, Anti-HBe, Anti-HBc,HBV-DNA; Hepatitis C: Anti-HCV,HCV-RNA)
• Participation in a clinical study or less than 1 month from the last dose of investigational drug to sign ICF;
• History of PD-1/PD-L1 or CTLA-4 therapy;
• Patients with drug abuse history or alcohol addiction history;

Sponsors & Collaborators

• Shandong New Time Pharmaceutical Co., LTD: lead

Study Sites (1)

Shaohong Yin

Linyi, Shandong, 276006, China

RECRUITING

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 31, 2018
• First Posted: September 5, 2018
• Study Start: March 1, 2019
• Primary Completion: February 8, 2021
• Study Completion: October 8, 2022
• Last Updated: October 22, 2020

Record last verified: 2020-10

Locations

CN (1)