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出境医 / 临床实验 / A Study of SHR-1501 in Patients With Advanced Tumors

A Study of SHR-1501 in Patients With Advanced Tumors

Study Description
Brief Summary:
The purpose of this study is to evaluate the safety and tolerability of SHR-1501 in patients with advanced malignancies .

Condition or disease Intervention/treatment Phase
Advanced Malignancies Drug: SHR-1501 Phase 1

Study Design
Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 48 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I Study on Tolerance, Safety and Pharmacokinetics of SHR-1501 in Patients With Advanced Malignancies.
Actual Study Start Date : October 30, 2019
Estimated Primary Completion Date : December 2020
Estimated Study Completion Date : December 2021
Arms and Interventions
Arm Intervention/treatment
Experimental: SHR-1501 dose escalation
SHR-1501 given subcutaneously
Drug: SHR-1501
Administered subcutaneously

Experimental: SHR-1501 dose expansion
SHR-1501 given subcutaneously
Drug: SHR-1501
Administered subcutaneously

Outcome Measures
Primary Outcome Measures :
  1. Dose-limiting toxicity [ Time Frame: Approximately 2 years ]
    Dose-limiting toxicity in patients with advanced tumors treated by SHR-1501.

  2. Maximum tolerated dose [ Time Frame: Approximately 2 years ]
    Maximum tolerated dose in patients with advanced tumors treated by SHR-1501.

  3. Adverse event/Serious adverse event [ Time Frame: Approximately 2 years ]
    Incidence/severity of adverse events/serious adverse events (rated based on CTC AE v5.0)


Secondary Outcome Measures :
  1. Pharmacokinetic (PK) [ Time Frame: Approximately 2 years ]
    Single dose: maximum concentration (Cmax)

  2. Pharmacokinetic (PK) [ Time Frame: Approximately 2 years ]
    Single dose: time to maximum concentration (Tmax)

  3. Pharmacokinetic (PK) [ Time Frame: Approximately 2 years ]
    Single dose: areas under the concentration-time curve (AUClast and AUCinf)

  4. Pharmacokinetic (PK) [ Time Frame: Approximately 2 years ]
    Single dose: half-life (t1/2)

  5. Pharmacokinetic (PK) [ Time Frame: Approximately 2 years ]
    Single dose: clearance (CL)

  6. Pharmacokinetic (PK) [ Time Frame: Approximately 2 years ]
    Single dose: mean residence time (MRT)

  7. Pharmacokinetic (PK) [ Time Frame: Approximately 2 years ]
    Single dose: volume at steady state (Vss)

  8. Pharmacokinetic (PK) [ Time Frame: Approximately 2 years ]
    Multiple doses (at steady state, if applicable): maximum concentration at steady state (Css_max)

  9. Pharmacokinetic (PK) [ Time Frame: Approximately 2 years ]
    Multiple doses (at steady state, if applicable):time to maximum concentration (Tmax)

  10. Pharmacokinetic (PK) [ Time Frame: Approximately 2 years ]
    Multiple doses (at steady state, if applicable):area under the concentration-time curve at steady state (AUCss)

  11. Pharmacokinetic (PK) [ Time Frame: Approximately 2 years ]
    Multiple doses (at steady state, if applicable): t1/2

  12. Pharmacokinetic (PK) [ Time Frame: Approximately 2 years ]
    Multiple doses (at steady state, if applicable):steady-state minimum concentration at steady state (Css_min)

  13. Pharmacokinetic (PK) [ Time Frame: Approximately 2 years ]
    Multiple doses (at steady state, if applicable):average concentration at steady state(Cavg)

  14. Pharmacokinetic (PK) [ Time Frame: Approximately 2 years ]
    Multiple doses (at steady state, if applicable):accumulation ratio (Rac)

  15. Immune-related biomarkers [ Time Frame: Approximately 2 years ]
    indicated by the count of CD8+ T-lymphocytes in peripheral blood at scheduled post-dose time points.

  16. Immune-related biomarkers [ Time Frame: Approximately 2 years ]
    indicated by the percentage of CD8+ T-lymphocytes in peripheral blood at scheduled post-dose time points.

  17. Immune-related biomarkers [ Time Frame: Approximately 2 years ]
    indicated by the count of natural killer (NK) cells in peripheral blood at scheduled post-dose time points.

  18. Immune-related biomarkers [ Time Frame: Approximately 2 years ]
    indicated by the percentage of natural killer (NK) cells in peripheral blood at scheduled post-dose time points.

  19. Objective response rate [ Time Frame: Approximately 2 years ]
    Percentage of participants with CR or PR.

  20. Disease control rate [ Time Frame: Approximately 2 years ]
    Percentage of participants with CR or PR or SD.

  21. Immunogenicity [ Time Frame: Approximately 2 years ]
    The immunogenicity of SHR-1501 single drug. The indicator includes number of participants with anti-drug antibody positive or neutralizing antibody positive.


Eligibility Criteria
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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:

  • All Patients All patients must meet all the following criteria to be eligible to participate:

    1. Voluntarily participate in this clinical study, understand the research procedure and be able to sign informed consent in writing;
    2. Subjects must be willing and able to follow the research protocol;
    3. Aged 18-70 years old when the informed consent form is signed;
    4. Have a histologically or cytologically confirmed diagnosis of advanced or metastatic tumor malignancy;
    5. Patients' malignancies must be relapsed or refractory to standard treatment, or patients cannot tolerate standard treatment, or patients have actively refused standard therapy;
    6. Eastern Cooperative Oncology Group ECOG PS score of 0-1;
    7. Have a life expectancy of ≥ 12 weeks;
    8. Adequate organ function defined according to the protocol, These results should be completed within 14 days prior to the first study treatment:
    9. Non-surgically sterilized women of childbearing age or male subjects are required to consent to the use of at least one medically approved contraceptive (eg intrauterine devices, contraceptives or condoms) is performed during the study treatment period and within 3 months of the end of the study treatment period.

Exclusion Criteria:

  1. Patients with cancerous meningitis (ie meningeal metastasis);
  2. Patients with active central nervous system (CNS) metastasis.
  3. Spinal cord compression that cannot be radically treated with surgery and/or radiotherapy cannot be enrolled.
  4. Patients with double primary cancers;
  5. Patients with a history of autoimmune diseases;
  6. Significant clinical significance in the history of cardiovascular disease;
  7. Arterial/venous thrombosis events such as cerebrovascular accidents deep vein thrombosis and pulmonary embolism within 6 months prior to first administration;
  8. Have a history of immunodeficiency including HIV infection;
  9. Active hepatitis B or hepatitis C patients;
  10. Any disease or symptom that is not appropriate for inclusion in this study determined by the investigator.;
  11. Patients have undergone major surgery within 28 days prior to the first dose (except for diagnostics);
  12. Those who used a live attenuated vaccine within 4 weeks prior to the first dose or expect a live attenuated vaccine during the study period;
  13. Those who received other clinical trials within 4 weeks prior to the first study;
  14. Those who received systemic immunosuppressive therapy within 2 weeks prior to the first study dose;
  15. Patients who have previously received allogeneic bone marrow transplantation or solid organ transplantation;
  16. A history of severe allergic reactions to other monoclonal antibody/fusion protein drugs;
  17. Mental illness, alcohol abuse, drug abuse or substance abuse;
  18. Any disease or condition that causes reasonable suspicion to prohibit the use of the study drug or affect the interpretation of the study results or the patient is at high risk of treatment complications (any other disease, metabolic disorder, physical examination results or laboratory tests abnormalities);
  19. Pregnant or lactating women or women planning to become pregnant during the study.
Contacts and Locations

Contacts
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Contact: Jianjun Zou, MD 021-68868570 zoujianjun@hrglobe.cn
Contact: Wei Shi, MD 021-68868570 shiwei@hrglobe.cn

Locations
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China
Cancer hospital, Chinese academy of medical sciences Recruiting
Beijing, China, 100021
Contact: Jing Huang, MD    010-67781331    huangjingwg@163.com   
Sponsors and Collaborators
Jiangsu HengRui Medicine Co., Ltd.
Investigators
Layout table for investigator information
Study Director: Jing Huang, MD Cancer Institute and Hospital, Chinese Academy of Medical Sciences
Tracking Information
First Submitted Date  ICMJE July 14, 2019
First Posted Date  ICMJE July 19, 2019
Last Update Posted Date July 22, 2020
Actual Study Start Date  ICMJE October 30, 2019
Estimated Primary Completion Date December 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 18, 2019)
  • Dose-limiting toxicity [ Time Frame: Approximately 2 years ]
    Dose-limiting toxicity in patients with advanced tumors treated by SHR-1501.
  • Maximum tolerated dose [ Time Frame: Approximately 2 years ]
    Maximum tolerated dose in patients with advanced tumors treated by SHR-1501.
  • Adverse event/Serious adverse event [ Time Frame: Approximately 2 years ]
    Incidence/severity of adverse events/serious adverse events (rated based on CTC AE v5.0)
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 18, 2019)
  • Pharmacokinetic (PK) [ Time Frame: Approximately 2 years ]
    Single dose: maximum concentration (Cmax)
  • Pharmacokinetic (PK) [ Time Frame: Approximately 2 years ]
    Single dose: time to maximum concentration (Tmax)
  • Pharmacokinetic (PK) [ Time Frame: Approximately 2 years ]
    Single dose: areas under the concentration-time curve (AUClast and AUCinf)
  • Pharmacokinetic (PK) [ Time Frame: Approximately 2 years ]
    Single dose: half-life (t1/2)
  • Pharmacokinetic (PK) [ Time Frame: Approximately 2 years ]
    Single dose: clearance (CL)
  • Pharmacokinetic (PK) [ Time Frame: Approximately 2 years ]
    Single dose: mean residence time (MRT)
  • Pharmacokinetic (PK) [ Time Frame: Approximately 2 years ]
    Single dose: volume at steady state (Vss)
  • Pharmacokinetic (PK) [ Time Frame: Approximately 2 years ]
    Multiple doses (at steady state, if applicable): maximum concentration at steady state (Css_max)
  • Pharmacokinetic (PK) [ Time Frame: Approximately 2 years ]
    Multiple doses (at steady state, if applicable):time to maximum concentration (Tmax)
  • Pharmacokinetic (PK) [ Time Frame: Approximately 2 years ]
    Multiple doses (at steady state, if applicable):area under the concentration-time curve at steady state (AUCss)
  • Pharmacokinetic (PK) [ Time Frame: Approximately 2 years ]
    Multiple doses (at steady state, if applicable): t1/2
  • Pharmacokinetic (PK) [ Time Frame: Approximately 2 years ]
    Multiple doses (at steady state, if applicable):steady-state minimum concentration at steady state (Css_min)
  • Pharmacokinetic (PK) [ Time Frame: Approximately 2 years ]
    Multiple doses (at steady state, if applicable):average concentration at steady state(Cavg)
  • Pharmacokinetic (PK) [ Time Frame: Approximately 2 years ]
    Multiple doses (at steady state, if applicable):accumulation ratio (Rac)
  • Immune-related biomarkers [ Time Frame: Approximately 2 years ]
    indicated by the count of CD8+ T-lymphocytes in peripheral blood at scheduled post-dose time points.
  • Immune-related biomarkers [ Time Frame: Approximately 2 years ]
    indicated by the percentage of CD8+ T-lymphocytes in peripheral blood at scheduled post-dose time points.
  • Immune-related biomarkers [ Time Frame: Approximately 2 years ]
    indicated by the count of natural killer (NK) cells in peripheral blood at scheduled post-dose time points.
  • Immune-related biomarkers [ Time Frame: Approximately 2 years ]
    indicated by the percentage of natural killer (NK) cells in peripheral blood at scheduled post-dose time points.
  • Objective response rate [ Time Frame: Approximately 2 years ]
    Percentage of participants with CR or PR.
  • Disease control rate [ Time Frame: Approximately 2 years ]
    Percentage of participants with CR or PR or SD.
  • Immunogenicity [ Time Frame: Approximately 2 years ]
    The immunogenicity of SHR-1501 single drug. The indicator includes number of participants with anti-drug antibody positive or neutralizing antibody positive.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of SHR-1501 in Patients With Advanced Tumors
Official Title  ICMJE A Phase I Study on Tolerance, Safety and Pharmacokinetics of SHR-1501 in Patients With Advanced Malignancies.
Brief Summary The purpose of this study is to evaluate the safety and tolerability of SHR-1501 in patients with advanced malignancies .
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Advanced Malignancies
Intervention  ICMJE Drug: SHR-1501
Administered subcutaneously
Study Arms  ICMJE
  • Experimental: SHR-1501 dose escalation
    SHR-1501 given subcutaneously
    Intervention: Drug: SHR-1501
  • Experimental: SHR-1501 dose expansion
    SHR-1501 given subcutaneously
    Intervention: Drug: SHR-1501
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: July 18, 2019)
48
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2021
Estimated Primary Completion Date December 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • All Patients All patients must meet all the following criteria to be eligible to participate:

    1. Voluntarily participate in this clinical study, understand the research procedure and be able to sign informed consent in writing;
    2. Subjects must be willing and able to follow the research protocol;
    3. Aged 18-70 years old when the informed consent form is signed;
    4. Have a histologically or cytologically confirmed diagnosis of advanced or metastatic tumor malignancy;
    5. Patients' malignancies must be relapsed or refractory to standard treatment, or patients cannot tolerate standard treatment, or patients have actively refused standard therapy;
    6. Eastern Cooperative Oncology Group ECOG PS score of 0-1;
    7. Have a life expectancy of ≥ 12 weeks;
    8. Adequate organ function defined according to the protocol, These results should be completed within 14 days prior to the first study treatment:
    9. Non-surgically sterilized women of childbearing age or male subjects are required to consent to the use of at least one medically approved contraceptive (eg intrauterine devices, contraceptives or condoms) is performed during the study treatment period and within 3 months of the end of the study treatment period.

Exclusion Criteria:

  1. Patients with cancerous meningitis (ie meningeal metastasis);
  2. Patients with active central nervous system (CNS) metastasis.
  3. Spinal cord compression that cannot be radically treated with surgery and/or radiotherapy cannot be enrolled.
  4. Patients with double primary cancers;
  5. Patients with a history of autoimmune diseases;
  6. Significant clinical significance in the history of cardiovascular disease;
  7. Arterial/venous thrombosis events such as cerebrovascular accidents deep vein thrombosis and pulmonary embolism within 6 months prior to first administration;
  8. Have a history of immunodeficiency including HIV infection;
  9. Active hepatitis B or hepatitis C patients;
  10. Any disease or symptom that is not appropriate for inclusion in this study determined by the investigator.;
  11. Patients have undergone major surgery within 28 days prior to the first dose (except for diagnostics);
  12. Those who used a live attenuated vaccine within 4 weeks prior to the first dose or expect a live attenuated vaccine during the study period;
  13. Those who received other clinical trials within 4 weeks prior to the first study;
  14. Those who received systemic immunosuppressive therapy within 2 weeks prior to the first study dose;
  15. Patients who have previously received allogeneic bone marrow transplantation or solid organ transplantation;
  16. A history of severe allergic reactions to other monoclonal antibody/fusion protein drugs;
  17. Mental illness, alcohol abuse, drug abuse or substance abuse;
  18. Any disease or condition that causes reasonable suspicion to prohibit the use of the study drug or affect the interpretation of the study results or the patient is at high risk of treatment complications (any other disease, metabolic disorder, physical examination results or laboratory tests abnormalities);
  19. Pregnant or lactating women or women planning to become pregnant during the study.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Jianjun Zou, MD 021-68868570 zoujianjun@hrglobe.cn
Contact: Wei Shi, MD 021-68868570 shiwei@hrglobe.cn
Listed Location Countries  ICMJE China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04025957
Other Study ID Numbers  ICMJE SHR-1501-I-102
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Jiangsu HengRui Medicine Co., Ltd.
Study Sponsor  ICMJE Jiangsu HengRui Medicine Co., Ltd.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Jing Huang, MD Cancer Institute and Hospital, Chinese Academy of Medical Sciences
PRS Account Jiangsu HengRui Medicine Co., Ltd.
Verification Date July 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP