Safety and Efficacy of Recombinant Humanized Anti-PD-1 mAb for Patients With Locally Advanced or Metastatic Melanoma
Primary Purpose
Advanced Melanoma, Metastatic Melanoma
Status
Unknown status
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
humanized anti-PD-1 monoclonal antibody toripalimab
Sponsored by
About this trial
This is an interventional treatment trial for Advanced Melanoma focused on measuring anti-PD-1 monoclonal antibody, advanced, metastatic, melanoma
Eligibility Criteria
Inclusion Criteria:
- Male and Female aged 18 and older are eligible;
- Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1;
- Histologic diagnosis of locally advanced or metastatic melanoma, while ocular melanoma is excluded, and the overall rate of mucousal melanoma is no more than 25%.
- Have failed at least 1 prior routine regimen for advanced disease.
- Providing with tumor specimen (for testing the expression of PD -L1 and the infiltrating lymphocytes);
- documentary evidence of BRAF mutation status;
- 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 >=3 months;
- Brain or meningeal metastases must be disposed with surgery or radiation, and be stable clinically for at least 3 months (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) PT/INR, aPTT≤1.5 x ULN;
- 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:
- Prior treatment with anti-PD-1/PD-L1/PD-L2 antibody;
- Hypersensitivity to recombinant humanized anti-PD-1 monoclonal Ab or its components.
- Prior treatment with mAb within past 4 weeks.
- 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;
- Positive tests for HIV, HCV, HBsAg or HBcAb with positive test for HBV DNA (>500IU/ml)
- History with 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 active CNS disease.
- meningeal carcinomatosis;
- Prior treatment with bone marrow stimulating factors,such as CSF (colony stimulating factor), EPO (erythropoietin), within past 2 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.
Sites / Locations
- Beijing Cancer Hospital
- Sun Yat-sen University Cancer center
- Wuhan Union Hospital
- The 81st Hospital of Chinese People's Liberation Army
- The First Hospital of Jilin University
- Yunnan Cancer Hospital
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
humanized anti-PD-1monoclonal antibody
Arm Description
humanized anti-PD-1 monoclonal antibody is to be injected intravenously 3mg/kg Q2w until disease progresses or unacceptable tolerability occurs
Outcomes
Primary Outcome Measures
Objective response rate (ORR) by RECIST 1.1 and irRECIST Objective response rate (ORR) by RECIST 1.1 and irRECIST
Secondary Outcome Measures
Duration of response (DOR) by RECIST1.1 and irRECIST
Progression free survival (PFS) by RECIST1.1 and irRECIST
Overall survival (OS)
Immunogenicity of anti-PD-1 monoclonal antibody
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Full Information
NCT ID
NCT03013101
First Posted
January 4, 2017
Last Updated
September 28, 2020
Sponsor
Shanghai Junshi Bioscience Co., Ltd.
1. Study Identification
Unique Protocol Identification Number
NCT03013101
Brief Title
Safety and Efficacy of Recombinant Humanized Anti-PD-1 mAb for Patients With Locally Advanced or Metastatic Melanoma
Official Title
A Phase II, Open, Multi-center and Single Arm Study Investigating Safety and Efficacy of Recombinant Humanized Anti-PD-1 mAb for Injection in Patients With Locally Advanced or Metastatic Melanoma and Standard Treatment Failure
Study Type
Interventional
2. Study Status
Record Verification Date
September 2020
Overall Recruitment Status
Unknown status
Study Start Date
December 28, 2016 (Actual)
Primary Completion Date
September 16, 2018 (Actual)
Study Completion Date
December 2021 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Shanghai Junshi Bioscience Co., Ltd.
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This is a multi-center, open-label, phase 2 study evaluating the humanized anti-PD-1 antibody JS001, as a monotherapy in patients with locally advanced or metastatic melanoma who have failed in routine systemic treatment.
Detailed Description
This is a multiple-center, open-label, phase 2 study evaluating the humanized anti-PD-1 antibody JS001, as a monotherapy in patients with locally advanced or metastatic melanoma who have failed in previous routine systemic treatment. Patients are injected with JS001 with 3mg/kg every 2 weeks until disease progresses or unacceptable toxicity occurs. Response assessment is conducted by every 8 weeks.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Advanced Melanoma, Metastatic Melanoma
Keywords
anti-PD-1 monoclonal antibody, advanced, metastatic, melanoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
128 (Actual)
8. Arms, Groups, and Interventions
Arm Title
humanized anti-PD-1monoclonal antibody
Arm Type
Experimental
Arm Description
humanized anti-PD-1 monoclonal antibody is to be injected intravenously 3mg/kg Q2w until disease progresses or unacceptable tolerability occurs
Intervention Type
Biological
Intervention Name(s)
humanized anti-PD-1 monoclonal antibody toripalimab
Other Intervention Name(s)
JS001, TAB001
Intervention Description
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.
Primary Outcome Measure Information:
Title
Objective response rate (ORR) by RECIST 1.1 and irRECIST Objective response rate (ORR) by RECIST 1.1 and irRECIST
Time Frame
3 years
Secondary Outcome Measure Information:
Title
Duration of response (DOR) by RECIST1.1 and irRECIST
Time Frame
3 years
Title
Progression free survival (PFS) by RECIST1.1 and irRECIST
Time Frame
3 years
Title
Overall survival (OS)
Time Frame
3 years
Title
Immunogenicity of anti-PD-1 monoclonal antibody
Time Frame
1.5 years
Title
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Time Frame
1.5 years
Other Pre-specified Outcome Measures:
Title
Correlation analysis of PD-L1 expression of tumor by Immunohistochemistry and ORR
Time Frame
3 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Male and Female aged 18 and older are eligible;
Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1;
Histologic diagnosis of locally advanced or metastatic melanoma, while ocular melanoma is excluded, and the overall rate of mucousal melanoma is no more than 25%.
Have failed at least 1 prior routine regimen for advanced disease.
Providing with tumor specimen (for testing the expression of PD -L1 and the infiltrating lymphocytes);
documentary evidence of BRAF mutation status;
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 >=3 months;
Brain or meningeal metastases must be disposed with surgery or radiation, and be stable clinically for at least 3 months (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) PT/INR, aPTT≤1.5 x ULN;
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:
Prior treatment with anti-PD-1/PD-L1/PD-L2 antibody;
Hypersensitivity to recombinant humanized anti-PD-1 monoclonal Ab or its components.
Prior treatment with mAb within past 4 weeks.
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;
Positive tests for HIV, HCV, HBsAg or HBcAb with positive test for HBV DNA (>500IU/ml)
History with 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 active CNS disease.
meningeal carcinomatosis;
Prior treatment with bone marrow stimulating factors,such as CSF (colony stimulating factor), EPO (erythropoietin), within past 2 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jun Guo, PhD, MD
Organizational Affiliation
Peking University Cancer Hospital & Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
Beijing Cancer Hospital
City
Beijing
State/Province
Beijing
ZIP/Postal Code
100142
Country
China
Facility Name
Sun Yat-sen University Cancer center
City
Guangzhou
State/Province
Guangdong
Country
China
Facility Name
Wuhan Union Hospital
City
Wuhan
State/Province
Hubei
Country
China
Facility Name
The 81st Hospital of Chinese People's Liberation Army
City
Nanjing
State/Province
Jiangsu
Country
China
Facility Name
The First Hospital of Jilin University
City
Changchun
State/Province
Jilin
Country
China
Facility Name
Yunnan Cancer Hospital
City
Kunming
State/Province
Yunnan
Country
China
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Citations:
PubMed Identifier
22658127
Citation
Topalian SL, Hodi FS, Brahmer JR, Gettinger SN, Smith DC, McDermott DF, Powderly JD, Carvajal RD, Sosman JA, Atkins MB, Leming PD, Spigel DR, Antonia SJ, Horn L, Drake CG, Pardoll DM, Chen L, Sharfman WH, Anders RA, Taube JM, McMiller TL, Xu H, Korman AJ, Jure-Kunkel M, Agrawal S, McDonald D, Kollia GD, Gupta A, Wigginton JM, Sznol M. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med. 2012 Jun 28;366(26):2443-54. doi: 10.1056/NEJMoa1200690. Epub 2012 Jun 2.
Results Reference
background
PubMed Identifier
24590637
Citation
Topalian SL, Sznol M, McDermott DF, Kluger HM, Carvajal RD, Sharfman WH, Brahmer JR, Lawrence DP, Atkins MB, Powderly JD, Leming PD, Lipson EJ, Puzanov I, Smith DC, Taube JM, Wigginton JM, Kollia GD, Gupta A, Pardoll DM, Sosman JA, Hodi FS. Survival, durable tumor remission, and long-term safety in patients with advanced melanoma receiving nivolumab. J Clin Oncol. 2014 Apr 1;32(10):1020-30. doi: 10.1200/JCO.2013.53.0105. Epub 2014 Mar 3.
Results Reference
background
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Safety and Efficacy of Recombinant Humanized Anti-PD-1 mAb for Patients With Locally Advanced or Metastatic Melanoma
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