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Safety and Tolerability of Recombinant Humanized Anti-PD-1 Monoclonal Antibody Toripalimab for Patients With Advanced Solid Tumors

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ClinicalTrials.gov Identifier: NCT02836795
Recruitment Status : Active, not recruiting
First Posted : July 19, 2016
Last Update Posted : March 11, 2019
Sponsor:
Information provided by (Responsible Party):
Shanghai Junshi Bioscience Co., Ltd.

Brief Summary:
This is a mono-center, open-label, phase 1 study evaluating the humanized anti-PD-1 antibody JS001, as a monotherapy in patients with advanced melanoma or urological cancers who have failed in routine systemic treatment. The study will be conducted in 2 parts: dose escalation and cohort expansion to investigate tolerability and efficacy.

Condition or disease Intervention/treatment Phase
Melanoma Urological Cancer Biological: humanized anti-PD-1 monoclonal antibody Toripalimab (JS001) Phase 1

Detailed Description:
This is a mono-center, open-label, phase 1 study evaluating the humanized anti-PD-1 antibody JS001, as a monotherapy in patients with advanced solid tumor (melanoma or urological cancers) who have failed in previous routine systemic treatment. The study will be conducted in 2 parts: dose escalation and cohort expansion. In the first part, nine patients are injected with different dosage of the humanized anti-PD-1 antibody (1mg/kg or 3mg/kg or 10mg/mg, three patients in one group ) once and observed carefully in the following 4 weeks. If no dose-limiting toxicity (DLT) occurs, then they are injected every 2 weeks until disease progresses or unacceptable toxicity occurs. This part is to confirm DLT, maximum tolerated dose (MTD) and recommended dose (RD). In the second part, 6-12 patients are enrolled in each dosage group and injected with the humanized anti-PD-1 antibody every 2 weeks until disease progresses or unacceptable toxicity occurs. This part is to further analyze safety and efficacy of the humanized anti-PD-1 antibody.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 35 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I, Open Label, Single Center and Dose Escalation Study Investigating Tolerance and Pharmacokinetics of Single and Multiple Doses of Recombinant Humanized Anti-PD-1 Monoclonal Antibody for Injection in Patients With Advanced Solid Tumors
Actual Study Start Date : April 2016
Actual Primary Completion Date : September 2018
Estimated Study Completion Date : September 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: humanized anti-PD-1 monoclonal antibody Toripalimab
humanized anti-PD-1 monoclonal antibody is to be injected intravenously 1mg/kg or 3mg/kg or 10mg/kg until disease progresses or unacceptable tolerability occurs.
Biological: humanized anti-PD-1 monoclonal antibody Toripalimab (JS001)
humanized anti-PD-1 monoclonal antibody (JS001) is a programmed death-1 (PD-1) immune checkpoint inhibitor antibody, which selectively interferes with the combination of PD-1 with its ligands, PD-L1 and PD-L2, resulting in the activation of lymphocytes and elimination of malignancy theoretically.
Other Name: JS001, TAB001




Primary Outcome Measures :
  1. Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 [ Time Frame: 1.5 years ]

Secondary Outcome Measures :
  1. PD-1 receptor occupancy of blood [ Time Frame: 1.5 years ]
  2. Objective Response Rate (ORR) by irRC and RECIST 1.1 [ Time Frame: 3 years ]
  3. Duration of Response (DOR) by irRC and RECIST 1.1 [ Time Frame: 3 years ]
  4. Disease Control Rate (DCR) by irRC and RECIST 1.1 [ Time Frame: 3 year ]
  5. Time to response (TTR) by irRC and RECIST 1.1 [ Time Frame: 3 years ]
  6. Progression-free survival(PFS) by irRC and RECIST 1.1 [ Time Frame: 3 years ]
  7. Overall survival (OS) by irRC and RECIST 1.1 [ Time Frame: 3 years ]
  8. Maximum Plasma Concentration (Cmax) after single dose injection of Anti-PD-1 Monoclonal Antibody (mAb) [ Time Frame: 1.5 years ]
  9. Peak Time (Tmax) after single dose injection of Anti-PD-1 mAb [ Time Frame: 1.5 years ]
  10. Area Under the Curve (AUC) after single dose injection of Anti-PD-1 mAb [ Time Frame: 1.5 years ]
  11. t1/2 after single dose injection of Recombinant Humanized Anti-PD-1 mAb [ Time Frame: 1.5 years ]
  12. Plasma clearance (CL) after single dose injection of Anti-PD-1 mAb [ Time Frame: 1.5 years ]
  13. Apparent volume of distribution (V) after single dose injection of Anti-PD-1 mAb [ Time Frame: 1.5 years ]
  14. Minimum Plasma Concentration (Cmin) of steady state after multiple dose injection of Anti-PD-1 mAb [ Time Frame: 1.5 years ]
  15. Average Plasma Concentration (Cav) of steady state after multiple dose injection of Anti-PD-1 mAb [ Time Frame: 1.5 years ]
  16. degree of fluctuation (DF) of steady state after multiple dose injection of Anti-PD-1 mAb [ Time Frame: 1.5 years ]
  17. Apparent volume of distribution of steady state (Vss) after multiple dose injection of Anti-PD-1 mAb [ Time Frame: 1.5 years ]

Other Outcome Measures:
  1. correlation analysis of PD-L1 expression of tumor and ORR [ Time Frame: 3 years ]
  2. correlation analysis of PD-L1 expression of tumor and DOR [ Time Frame: 3 years ]
  3. correlation analysis of PD-L1 expression of tumor and DCR [ Time Frame: 3 years ]
  4. correlation analysis of PD-L1 expression of tumor and TTR [ Time Frame: 3 years ]
  5. correlation analysis of PD-L1 expression of tumor and PFS [ Time Frame: 3 years ]
  6. correlation analysis of PD-L1 expression of tumor and OS [ Time Frame: 3 years ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male and Female aged 18 to 70 years are eligible;
  • Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1
  • Histologic diagnosis of unresectable melanoma or urological cancer. Have failed at least 1 prior routine regimen for metastatic disease, or failed to tolerate the toxicity, or lack of any routine regimens.
  • Providing with tumor specimen (for testing the expression of PD -L1 and the infiltrating lymphocytes);
  • At least 1 measurable lesion (only 1 measurable lymph node lesion is excluded) (routine CT scan >=20mm, spiral CT scan >=10mm, no prior radiation to measurable lesions) Predicted survival >=6 months;
  • Brain or meningeal metastases must be disposed with surgery or radiation, and be stable clinically for at least 8 weeks (prior systemic steroids was allowed, but concurrent administration of systemic steroids with the study drug is excluded).
  • Screening laboratory values must meet the following criteria(within past 14 days):

hemoglobin ≥ 9.0 g/dL neutrophils ≥ 1500 cells/ µL platelets ≥ 100 x 10^3/ µL total bilirubin ≤ 1.5 x upper limit of normal (ULN) aspartic transaminase (AST) and alanine transaminase (ALT) ≤ 2.5 x ULN without, and ≤ 5 x ULN with hepatic metastasis serum creatinine ≤1╳ULN,creatinine clearance >50ml/min (Cockcroft-Gault equation)

  • Without systemic steroids within past 4 weeks
  • Males or female of childbearing potential must: agree to use using a reliable form of contraception (eg, oral contraceptives, intrauterine device, control sex desire, double barrier method of condom and spermicidal) during the treatment period and for at least 12 months after the last dose of study drug.
  • Must have read, understood, and provided written informed consent voluntarily. Willing to adhere to the study visit schedule and the prohibitions and restrictions specified in this protocol.

Exclusion Criteria:

  • Hypersensitivity to recombinant humanized anti-PD-1 monoclonal Ab or its components.
  • Prior treatment with mAb within past 3 months (locally administration excluded)
  • Prior antitumor therapy (including corticosteroids and immunotherapy) or participation in other clinical trials within past 4 weeks, or have not recovered from toxicities since the last treatment;
  • Pregnant or nursing
  • Abnormal Blood coagulation
  • Positive tests for HIV, HCV, HBsAg or HBcAb with positive test for HBV DNA (>500IU/ml)
  • History with pulmonary tuberculosis;
  • Patients with any active autoimmune disease or a documented history of autoimmune disease, or history of syndrome that required systemic steroids or immunosuppressive medications, such as hypophysitis, pneumonia, colitis, hepatitis, nephritis, hyperthyroidism or hypothyroidism.
  • Severe, uncontrolled medical condition that would affect patients' compliance or obscure the interpretation of toxicity determination or adverse events, including active severe infection, uncontrolled diabetes, angiocardiopathy (heart failure > class II NYHA, heart block >II grade, myocardial infarction, unstable arrhythmia or unstable angina within past 6 months, cerebral infarction within past 3 months) or pulmonary disease ( interstitial pneumonia, obstructive pulmonary disease or symptomatic bronchospasm).
  • Evidence with CNS disease.
  • Prior treatment with bone marrow stimulating factors,such as CSF (colony stimulating factor), EPO (erythropoietin), within past 1 weeks
  • Prior live vaccine therapy within past 4 weeks.
  • Prior major surgery within past 4 weeks (diagnostic surgery excluded).
  • Psychiatric medicines abuse without withdrawal, or history of psychiatric illness.
  • Prior malignancy active within the previous 5 years except for locally curable cancers that have been apparently cured, such as basal cell skin cancer or carcinoma in situ of the cervix.
  • Underlying medical condition that, in the Investigator's opinion, would increase the risks of study drug administration or obscure the interpretation of toxicity determination or adverse events.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02836795


Locations
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China, Beijing
Beijing Cancer Hospital
Beijing, Beijing, China, 100142
Sponsors and Collaborators
Shanghai Junshi Bioscience Co., Ltd.
Investigators
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Principal Investigator: Jun Guo, Phd MD Beijing Cancer Hospital

Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Shanghai Junshi Bioscience Co., Ltd.
ClinicalTrials.gov Identifier: NCT02836795     History of Changes
Other Study ID Numbers: Junshi-JS001-BJZL-I
First Posted: July 19, 2016    Key Record Dates
Last Update Posted: March 11, 2019
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes

Keywords provided by Shanghai Junshi Bioscience Co., Ltd.:
anti-PD-1 monoclonal antibody
advanced solid tumors
safety

Additional relevant MeSH terms:
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Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Antibodies
Immunoglobulins
Antibodies, Monoclonal
Antineoplastic Agents, Immunological
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents