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The Study to Evaluate JS001 in Patients With Advanced GC, ESCC, NPC, HNSCC

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ClinicalTrials.gov Identifier: NCT02915432
Recruitment Status : Recruiting
First Posted : September 27, 2016
Last Update Posted : November 27, 2018
Sponsor:
Information provided by (Responsible Party):
Shanghai Junshi Bioscience Co.,Ltd.

Brief Summary:
The purpose of this study is to preliminarily evaluate anti-tumor activity of a Recombinant Humanized Anti-PD-1 Monoclonal Antibody for Infusion (JS001) in treating advanced gastric adenocarcinoma, esophageal squamous cell carcinoma, nasopharyngeal carcinoma and head and neck squamous cell carcinoma and to determine the recommended phase II dose (RP2D)

Condition or disease Intervention/treatment Phase
Gastric Adenocarcinoma Esophageal Squamous Cell Carcinoma Nasopharyngeal Carcinoma Head and Neck Squamous Cell Carcinoma Biological: 3 mg/kg anti-PD-1 mAb JS001 Q2W Biological: 360 mg anti-PD-1 mAb JS001 Q3W Phase 1 Phase 2

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 326 participants
Allocation: Non-Randomized
Intervention Model: Factorial Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Multi-Center, Open Label Phase Ib/II Clinical Study to Evaluate JS001 in Patients With Advanced Gastric Adenocarcinoma, Esophageal Squamous Cell Carcinoma, Nasopharyngeal Carcinoma and Head and Neck Squamous Cell Carcinoma
Study Start Date : December 2016
Estimated Primary Completion Date : June 30, 2019
Estimated Study Completion Date : October 31, 2019


Arm Intervention/treatment
Experimental: 3 mg/kg anti-PD-1 mAb JS001 Q2W
Subjects will be eligible for this study after they fulfill the inclusion criteria and exclusion criteria. Subjects diagnosed as the gastric adenocarcinoma, esophageal squamous cell carcinoma, nasopharyngeal carcinoma, or head and neck squamous cell carcinoma will receive treatment at the dose of 3 mg/kg.
Biological: 3 mg/kg anti-PD-1 mAb JS001 Q2W

This study is planned to conduct the 3 mg/kg dose group study at first. After enrollment, the subjects will be administered every 2 weeks (Q2W) with 4 weeks as a cycle, until absence of further benefits, acceptable toxicity, investigator decision, consent withdrawal or death.

If patient experiences 1st onset of disease progression and investigator judges that patient will obtain clinical benefit from the study treatment, patient can continue the study treatment after the discussion between investigator and medical monitor from sponsor or authorized CRO and approval is obtained afterwards. If the subject develops 2nd disease progression after 1st disease progression, he/she should permanently withdraw from the study treatment.

Other Name: TAB001

Experimental: 360 mg anti-PD-1 mAb JS001 Q3W
Subjects will receive corresponding regimen of standard first-line chemotherapy combined with JS001 360 mg once every 3 weeks (Q3W). JS001 360 mg Q3W can be administrated after the end of chemotherapy until absence of further benefits judged by the investigator, disease progression, occurrence of intolerable toxicity, investigator's decision, and withdrawal of informed consent by the subject, or death.
Biological: 360 mg anti-PD-1 mAb JS001 Q3W
Subjects will receive corresponding regimen of standard first-line chemotherapy combined with JS001 360 mg once every 3 weeks (Q3W). JS001 360 mg Q3W can be administrated after the end of chemotherapy until absence of further benefits judged by the investigator, disease progression, occurrence of intolerable toxicity, investigator's decision, and withdrawal of informed consent by the subject, or death.
Other Name: TAB001




Primary Outcome Measures :
  1. Objective response rate (ORR) evaluated based on Response Evaluation Criteria in Solid Tumors (RECIST 1.1) [ Time Frame: Up to 1.5 approximately years ]

Secondary Outcome Measures :
  1. Objective response rate (ORR) evaluated based on Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) [ Time Frame: Up to 1.5 approximately years ]
  2. Duration of response (DOR) [ Time Frame: Up to 1.5 approximately years ]
  3. Disease control rate (DCR) [ Time Frame: Up to 1.5 approximately years ]
  4. Progression Free Survival (PFS) [ Time Frame: Up to 1.5 approximately years ]
  5. Overall Survival (OS) [ Time Frame: Up to 2.5 approximately years ]
  6. The proportion of patients without progression within 6 months after first dosing (6M PFS %) [ Time Frame: Up to 1.5 years ]
  7. The proportion of patients who are survival within 1 year after first dosing (1YR OS %) [ Time Frame: Up to 2.5 years ]
  8. Safety: incidence and severity of adverse events, and abnormal laboratory examination results with clinical significance [ Time Frame: Up to 1.5 approximately years ]
  9. The frequency of positive or negative Anti-drug Antibody (ADA) test comparing with baseline [ Time Frame: Up to 6 approximately mouths ]
  10. Peak serum concentration (Cmax) and dose-normalized Cmax (Cmax/D) [ Time Frame: 6 mouths ]
  11. Area under the serum concentration−time curve from time zero to last dosing (AUC0-tau) and dose-normalized AUC0-tau (AUC0-tau/D) [ Time Frame: 6 mouths ]
  12. Area under the serum concentration−time curve (AUC0-t) and dose-normalized AUC0-t (AUC0-t/D) [ Time Frame: 6 mouths ]
  13. AUC from time zero to infinity (AUC0-∞) [ Time Frame: 6 mouths ]
  14. Time to Peak (Tmax) [ Time Frame: 6 mouths ]
  15. Terminal elimination rate constant (λz) and terminal half-life (t1/2) [ Time Frame: 6 mouths ]
  16. Apparent Volume of Distribution (Vd) [ Time Frame: 6 mouths ]
  17. Volume of Distribution at Steady State (Vdss) [ Time Frame: 6 mouths ]
  18. Total Body Clearance (CL) [ Time Frame: 6 mouths ]
  19. Mean Residence Time (MRT) [ Time Frame: 6 mouths ]
  20. Accumulative rate of Cmax (ARCmax) [ Time Frame: 6 mouths ]
  21. Accumulative Rate of AUC0-t (ARAUC0-t) [ Time Frame: 6 mouths ]
  22. Accumulative Rate of AUC0-tau (ARAUC0-tau) [ Time Frame: 6 mouths ]
  23. Linear Index (LI) [ Time Frame: 6 mouths ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Fully understand the study and sign the Informed Consent Form (ICF) voluntarily;
  2. Patients with histologically and/or cytologically diagnosed as advanced gastric adenocarcinoma (including adenocarcinoma at esophageal-gastric conjunction), esophageal squamous cell carcinoma, nasopharyngeal carcinoma, head and neck squamous cell carcinoma, and who meet the following conditions:

    • Patients with gastric adenocarcinoma must have received at least one line of anti-tumor treatment for advanced gastric adenocarcinoma and have tumor progression documented or be intolerable to the current chemotherapy regimen. Patients who have recurrence or metastasis within 6 months after completion of adjuvant or neoadjuvant chemotherapy are eligible to this study;
    • Patients with esophageal squamous cell carcinoma must have received at least one line of treatment for advanced esophageal squamous cell carcinoma (including but not limited to anticancer drug treatment or concomitant radio-chemotherapy) and have tumor progression documented or be intolerable to the current chemotherapy regimen. Patients who have recurrence or metastasis within 6 months after completion of adjuvant or neoadjuvant therapy (including but not limited to chemotherapy or concomitant radio-chemotherapy) accompanied by the radical operation are eligible to this study;
    • Patients with nasopharyngeal carcinoma or head and neck squamous cell carcinoma who have received at least one line of treatment for advanced nasopharyngeal carcinoma or head and neck squamous cell carcinoma (including but not limited to anticancer drug treatment or concomitant radio-chemotherapy) and have tumor progression documented or be intolerable to other current chemotherapy regimens. Patients with recurrence or metastasis within 6 months after completion of adjuvant or neoadjuvant concomitant radio-chemotherapy are eligible to this study.
  3. Have at least one measurable lesion (according to RECIST 1.1); Note: Lesion with radiotherapy treated previously can't be regarded as a target lesion, unless which has definite progressed after radiotherapy.
  4. Agree to provide the archived tumor tissue specimens or have biopsy to collect tumor tissues in order to send them t for PD-L1 IHC measurement in central lab;
  5. Male or female aged between 18 to 75 years of old;
  6. ECOG score: 0-1;
  7. Estimated survival duration ≥ 3 months;
  8. The laboratory examination results obtained within 7 days prior to enrollment must meet the following criteria:

    1. Neutrophil ≥1.5×109/L;
    2. Platelet ≥75×109/L;
    3. Hemoglobin ≥90 g/L (without infusion of concentrated red blood cells within 2 weeks);
    4. Serum creatinine ≤ 1.5× ULN, or creatinine clearance > 50 mL/min;
    5. Total serum bilirubin ≤ 1.5×ULN (total bilirubin ≤ 3×ULN are acceptable for patients with Gilbert syndrome);
    6. Both AST and ALT ≤ 2.5×ULN; ALT and AST≤5×ULN are acceptable for patients with liver metastasis;
  9. Negative serum pregnancy result must be confirmed in women of childbearing potential within 21 days prior to enrollment and agree to take effective contraception measures during study treatment period and within 28 days after the end of study treatment. Women of childbearing potential are defined as women with sexual maturity who meet any of the following conditions: 1) have no hysterectomy or bilateral oophorectomy; 2) without natural menopause more than consecutive 24 months (patients with menopause after cancer treatment may also have childbearing potential) (i.e. menstruation occurred at any time during the previous consecutive 24 months).

Exclusion Criteria:

  1. Known to be allergic to citric acid monohydrate, dihydrate sodium citrate, mannitol or polysorbate (components of the investigational drug);
  2. Received anti-tumor treatment with cytotoxic drugs, biological drugs (e.g. monoclonal antibody), immunotherapy (e.g. interleukin 2 or interferon);
  3. Received tyrosine kinase inhibitor treatment within 2 weeks prior to enrollment;
  4. Received radiotherapy within 4 weeks prior to enrollment, or received treatment with radioactive drugs within 8 weeks prior to enrollment. However, local palliative radiotherapy for bone metastasis lesions should be excluded;
  5. Received major surgical operation within 4 weeks prior to enrollment or have not completely recovered from the prior operation (For the definition of major surgical operation, please refer to the Level 3 and Level 4 operations stipulated in the Management of Clinical Application of Medical Technology enforced on May 1, 2009);
  6. Toxicity due to any previous anticancer treatment has not recovered to CTCAE [Version 4.03] Grade 0-1, excluding the following conditions:

    1. Alopecia;
    2. Pigmentation;
    3. Peripheral nerve toxicity has recovered to ≤ CTCAE Grade 2;
    4. Long-term toxicity related to radiotherapy won't be fully recovered as judged by investigator.
  7. Have central nervous system metastasis with clinical symptoms (e.g. brain edema, demand of hormone intervention, or progression of brain metastasis) and/or carcinomatous meningitis. Patients received treatment for brain or meningeal metastasis previously can be included if they have remained stable clinically for at least 2 months and systemic glucocorticoid treatment (Prednisone with dose >10 mg/day or other equivalent formulations) has been discontinued for more than 4 weeks;
  8. Patients with nasopharyngeal carcinoma or head and neck squamous cell carcinoma are found to have necrotic lesions by examination within 4 weeks prior to enrollment, for which there is a potential risk of massive hemorrhage as judged by investigator;
  9. Had/Have other malignant tumor previously or currently (expect for effectively controlled non-melanoma skin basal cell carcinoma, breast/cervix carcinoma in situ, and other malignant tumors which were effectively controlled without treatment over the past 5 years);
  10. Patients having any active autoimmune disease or history of autoimmune disease (including but not limited to interstitial pneumonia, uveitis, enteritis, hepatitis, hypophysitis, nephritis, hyperthyroidism or hypothyroidism. Patients with vitiligo or asthma (in childhood) was completely resolved and without need of any intervention in adulthood can be included. Patients with asthma which needs bronchodilator for medical intervention cannot be included);
  11. Have been treated by anti-PD-1 antibody, anti-PD-L1 antibody, anti-PD-L2 antibody or anti-CTLA-4 antibody (or any other antibody which acts on T-cell co-stimulatory or checkpoint pathway) previously;
  12. Patients are diagnosed as active tuberculosis (TB) and receiving anti-tuberculosis therapy or used to have anti-tuberculosis therapy within 1 year prior to screening;
  13. Have concomitant diseases that require long-term treatment with immunosuppressive drugs, or need corticosteroids at an effective immunosuppressive dose for systemic or local treatment purpose;
  14. Received any anti-infection vaccine (e.g. influenza vaccine, varicella vaccine, etc.) within 4 weeks prior to enrollment;
  15. Pregnant or lactating women
  16. HIV positive;
  17. HBsAg positive with HBV DNA copies detected as positive (quantitative measures ≥ 1000 cps/ml);
  18. Positive for chronic Hepatitis C in blood screening test (HCV antibody positive);
  19. Any other clinical significant disease or condition, as evaluated by the investigator, may affect the protocol compliance, or inform consent process or not suitable to participate into this clinical trial.

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): NCT02915432


Contacts
Contact: Feng Li +8618627721499 feng_li@topalliancebio.com

  Show 23 Study Locations
Sponsors and Collaborators
Shanghai Junshi Bioscience Co.,Ltd.
Investigators
Principal Investigator: Ruihua Xu, MD, PhD Sun Yat-sen University

Responsible Party: Shanghai Junshi Bioscience Co.,Ltd.
ClinicalTrials.gov Identifier: NCT02915432     History of Changes
Other Study ID Numbers: Junshi-JS001-Ib/II
First Posted: September 27, 2016    Key Record Dates
Last Update Posted: November 27, 2018
Last Verified: September 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Shanghai Junshi Bioscience Co.,Ltd.:
Anti PD-1
JS001
Gastric Adenocarcinoma
Esophageal Squamous Cell Carcinoma
Nasopharyngeal Carcinoma
Head and Neck Squamous Cell Carcinoma
Simon's Two Stage
ORR

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Squamous Cell
Adenocarcinoma
Nasopharyngeal Neoplasms
Head and Neck Neoplasms
Esophageal Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell
Pharyngeal Neoplasms
Otorhinolaryngologic Neoplasms
Neoplasms by Site
Nasopharyngeal Diseases
Pharyngeal Diseases
Stomatognathic Diseases
Otorhinolaryngologic Diseases
Gastrointestinal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Esophageal Diseases
Gastrointestinal Diseases