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

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ClinicalTrials.gov Identifier: NCT02915432
Recruitment Status : Active, not recruiting
First Posted : September 27, 2016
Last Update Posted : October 23, 2019
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 Biological: 240mg anti-PD-1 mAb JS001 Q3W Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 403 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
Actual Study Start Date : December 2016
Actual Primary Completion Date : September 30, 2019
Estimated Study Completion Date : October 31, 2021


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: toripalimab, 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: toripalimab, TAB001

Experimental: 240mg anti-PD-1 mAb JS001 Q3W
Subjects will receive corresponding regimen of standard first-line chemotherapy combined with JS001 240 mg once every 3 weeks (Q3W). JS001 240 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: 240mg anti-PD-1 mAb JS001 Q3W
Subjects will receive corresponding regimen of standard first-line chemotherapy combined with JS001 240 mg once every 3 weeks (Q3W). JS001 240 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: toripalimab, 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 ]
    To preliminarily evaluate the anti-tumor activity of Toripalimab Injection (former name: Recombinant humanized anti-PD-1 monoclonal antibody for injection, JS001) in treating advanced gastric adenocarcinoma, esophageal squamous cell carcinoma, nasopharyngeal carcinoma, and head and neck squamous cell carcinoma.


Secondary Outcome Measures :
  1. Duration of response (DOR) [ Time Frame: Up to 1.5 approximately years ]
  2. Disease control rate (DCR) [ Time Frame: Up to 1.5 approximately years ]
  3. Progression free survival (PFS) [ Time Frame: Up to 1.5 approximately years ]
  4. Overall survival (OS) [ Time Frame: Up to 1.5 approximately years ]
  5. afety: incidence and severity of adverse events, and clinically significant laboratory abnormalities [ Time Frame: Up to 1.5 approximately years ]
  6. The frequencies of positive and negative anti-drug antibody (ADA) test compared with baseline [ Time Frame: Up to 1.5 approximately years ]
  7. Maximum Plasma Concentration (Cmax) after single dose injection of Anti-PD-1 Monoclonal Antibody (mAb) [ Time Frame: Up to 1.5 approximately years ]
  8. Peak Time (Tmax) after single dose injection of Anti-PD-1 mAb [ Time Frame: Up to 1.5 approximately years ]
  9. Area Under the Curve (AUC) after single dose injection of Anti-PD-1 mAb [ Time Frame: Up to 1.5 approximately years ]
  10. t1/2 after single dose injection of Recombinant Humanized Anti-PD-1 mAb [ Time Frame: Up to 1.5 approximately years ]
  11. Plasma clearance (CL) after single dose injection of Anti-PD-1 mAb [ Time Frame: Up to 1.5 approximately years ]
  12. Apparent volume of distribution (V) after single dose injection of Anti-PD-1 mAb [ Time Frame: Up to 1.5 approximately years ]
  13. Minimum Plasma Concentration (Cmin) of steady state after multiple dose injection of Anti-PD-1 mAb [ Time Frame: Up to 1.5 approximately years ]
  14. Apparent volume of distribution of steady state (Vss) after multiple dose injection of Anti-PD-1 mAb [ Time Frame: Up to 1.5 approximately years ]

Other Outcome Measures:
  1. Correlation between PD-L1 expression in tumor tissue and the anti-tumor activity of JS001 demonstrated in the analysis [ Time Frame: Up to 1.5 approximately years ]
  2. Correlation between EBV expression in tumor tissue of esophageal squamous cell carcinoma and gastric adenocarcinoma and the anti-tumor activity of JS001 demonstrated in the analysis [ Time Frame: Up to 1.5 approximately years ]
  3. Correlation between EBV expression in tumor tissue and blood of nasopharyngeal carcinoma and the anti-tumor activity of JS001 demonstrated in the analysis [ Time Frame: Up to 1.5 approximately years ]
  4. Correlation between HPV expression in tumor tissue of head and neck squamous cell carcinoma and the anti-tumor activity of JS001 demonstrated in the analysis [ Time Frame: Up to 1.5 approximately years ]
  5. Correlation between MSI expression in tumor tissue of esophageal squamous cell carcinoma and gastric adenocarcinoma and the anti-tumor activity of JS001 demonstrated in the analysis [ Time Frame: Up to 1.5 approximately years ]
  6. Correlation between the expression of other potential pharmacodynamic indexes and the anti-tumor activity of JS001 demonstrated in the analysi [ Time Frame: Up to 1.5 approximately years ]
  7. Correlation of the changes of TBNK lymphocytes subgroup in patients receiving chemotherapy combined with JS001 and its correlation with the anti-tumor activity [ Time Frame: Up to 1.5 approximately years ]


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 Subjects may be entered in the study only if they meet all of the following criteria:

  1. Fully understand the study and signed the Informed Consent Form (ICF) voluntarily;
  2. Subjects with histologically and/or cytologically confirmed advanced and/or metastatic gastric adenocarcinoma (including adenocarcinoma at esophageal-gastric conjunction), esophageal squamous cell carcinoma, nasopharyngeal carcinoma, or head and neck squamous cell carcinoma, who meet the following conditions (not applicable to cohort 5, 6, 7, and 8):

    Subjects with gastric adenocarcinoma must have received at least one line of anti-tumor treatment for advanced gastric adenocarcinoma and have documented tumor progression or be intolerable to the current available chemotherapy regimen. Subjects who have recurrence or metastasis within 6 months after completion of concomitant adjuvant or neoadjuvant chemotherapy of radical operation are eligible to this study; Subjects 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 radio-chemotherapy) and have documented tumor progression or be intolerable to the current chemotherapy regimen. Subjects who have recurrence or metastasis within 6 months after completion of concomitant adjuvant or neoadjuvant therapy (including but not limited to chemotherapy or radio-chemotherapy) of radical operation are eligible to this study;

    Subjects 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 radio-chemotherapy) and have documented tumor progression or be intolerable to other current chemotherapy regimens. Subjects with recurrence or metastasis within 6 months after completion of concomitant adjuvant or neoadjuvant radio-chemotherapy of radical operation are eligible to this study (only applies for Version 4.1 and the previous ones); while for the working protocol version 5.0, subjects with nasopharyngeal carcinoma can be enrolled only if they meet the following criteria:

    subjects having received at least two lines of treatment for advanced nasopharyngeal carcinoma (including but not limited to anticancer drug treatment and radio-chemotherapy), who are confirmed to have tumor progression or be intolerable to other current chemotherapy regimens; adjuvant or neoadjuvant radio-chemotherapy after radical surgery can be considered as one line of treatment if tumor recurrence or metastasis occurred within 6 months after the end of the radio-chemotherapy.

  3. At least one measurable lesion (according to RECIST 1.1); Note: Any lesion which received radiotherapy treatment previously cannot be regarded as a target lesion, unless that it has definitely progressed after radiotherapy.
  4. Agree to provide archived tumor tissue specimens or have biopsy to collect tumor tissues for PD-L1 IHC measurement in the central laboratory;
  5. Males or females aged between 18 and 75 years old;
  6. ECOG score of 0-1;
  7. Life expectancy ≥ 3 months;
  8. The results of laboratory tests performed within 7 days prior to enrollment must meet the following criteria:

    1. Neutrophils ≥ 1.5×109/L (not applicable to cohort 5, 6, 7, and 8);
    2. Platelets ≥ 75×109/L (not applicable to cohort 5, 6, 7, and 8);
    3. Hemoglobin ≥ 90 g/L (without receiving infusion of concentrated red blood cells within 2 weeks);
    4. Serum creatinine ≤ 1.5× upper limit of normal (ULN), or creatinine clearance > 50 mL/min (not applicable to cohort 5, 6, 7, and 8);
    5. Serum total bilirubin ≤ 1.5×ULN (total bilirubin ≤ 3×ULN are acceptable for subjects with Gilbert syndrome);
    6. Both AST and ALT ≤ 2.5×ULN; ALT and AST ≤ 5×ULN are acceptable for subjects with liver metastasis;
  9. Serum pregnancy test result must be confirmed as negative for women of childbearing potential within 28 days prior to enrollment and the subjects must agree to take effective contraception measures throughout the study treatment period until 60 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) no hysterectomy or bilateral oophorectomy; 2) without natural menopause for a 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) (not applicable to cohort 5, 6, 7, and 8).

Female partners of childbearing potential of the male subjects should also follow the contraception requirements.

Other special inclusion criteria for cohort 5, 6, 7, and 8.

  1. Subjects with histologically and/or cytologically confirmed advanced and/or metastatic gastric adenocarcinoma (including adenocarcinoma at esophageal-gastric conjunction), esophageal squamous cell carcinoma, nasopharyngeal carcinoma, or head and neck squamous cell carcinoma, who meet any of the following conditions:

    1. Subjects who have not received any systematic treatment.
    2. Subjects who have received any neoadjuvant chemotherapy, adjuvant chemotherapy for the purpose of curing must experience a period for at least 6 months from the end of the last chemotherapy to tumor progression.
    3. Subjects with head and neck squamous cell carcinoma must have received radiotherapy for the purpose of curing, and the period from the end of radiotherapy to tumor progression must be at least 1 year.
    4. For subjects with gastric carcinoma, Her2 negative is required. HER2 positive is defined as IHC 3+ or IHC 2+ combined with ISH+, and ISH positive is defined as the ratio of the number of HER2 gene copies to the number of CEP17 signals ≥ 2.0.
  2. Results of laboratory test conducted within 7 days before enrollment must meet the following criteria:

    1. Neutrophils ≥ 2×109/L; WBC count ≥ 4×109L and < 15×109/L
    2. Platelets ≥ 100×109/L;
    3. Hemoglobin ≥ 90 g/L (no infusion of concentrated red blood cells within 2 weeks);
    4. Creatinine clearance rate > 60 mL/min, based on the predicted value of Cockcroft-Gault glomerular filtration rate:

      (140 - age) × (weight, kg) × (0.85, if females) 72× (serum creatinine, mg/dL) Or: (140 - age) × (weight, kg) × (0.85, if females) 0.818 × (serum creatinine, μmol/L)

    5. Serum total bilirubin ≤ 1.5 × ULN (total bilirubin ≤ 3 × ULN are acceptable for subjects with Gilbert syndrome);
    6. INR and aPTT ≤ 1.5 × ULN, applies only to subjects who have not received anticoagulation; and for subjects who are receiving anticoagulation, the dose for anticoagulation must be stable.
  3. Serum pregnancy test result must be confirmed as negative for women of childbearing potential within 28 days prior to enrollment and the subjects must agree to take effective contraception measures throughout the study treatment period until 6 months after the end of chemotherapy or 60 days after the end of study treatment (whichever comes last). Women of childbearing potential are defined as women with sexual maturities, who meet any of the following conditions: 1) no hysterectomy or bilateral oophorectomy; 2) without natural menopause for a 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) .

Female partners of childbearing potential of the male subjects should also follow the contraception requirements.

Subjects fulfilling any of the following conditions cannot be enrolled in the study:

  1. Known hypersensitivity to citric acid monohydrate, dihydrate sodium citrate, mannitol or polysorbate (components of the investigational drug);
  2. Anti-tumor treatment with cytotoxic drugs, biological drugs (e.g. monoclonal antibody), immunotherapy (e.g. interleukin 2 or interferon), or other investigational drugs within 4 weeks prior to enrollment;
  3. Tyrosine kinase inhibitor treatment within 2 weeks prior to enrollment;
  4. Radiotherapy within 4 weeks prior to enrollment, or radioactive drugs within 8 weeks prior to enrollment. However, patients receiving local palliative radiotherapy for bone metastasis lesions can be included;
  5. Subjects with any major surgical operation within 4 weeks prior to enrollment or who 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 Grade 0-1, excluding the following conditions:

    1. Alopecia;
    2. Pigmentation;
    3. Peripheral nerve toxicity recovered to < CTCAE Grade 2 (not applicable to cohort 5, 6, 7, and 8, subjects are not eligible if peripheral neurotoxicity does not restore to normal);
    4. Long-term toxicity related to radiotherapy, which will not fully recover as judged by the investigator.
  7. Central nervous system metastasis with clinical symptoms (e.g. brain edema, hormone intervention required, or progression of brain metastasis) and/or carcinomatous meningitis. Subjects with prior treatment for brain or meningeal metastasis can be included if they have remained stable clinically for at least 2 months and systemic hormone treatment (Prednisone at a dose of > 10 mg/day or other equivalent hormone formulations) has been discontinued for more than 4 weeks;
  8. Subjects with nasopharyngeal carcinoma or head and neck squamous cell carcinoma, who 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 the investigator;
  9. Previous or other concurrent malignant tumors (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. Any active autoimmune disease or history of any autoimmune disease (including but are not limited to interstitial pneumonia, uveitis, enteritis, hepatitis, hypophysitis, nephritis, hyperthyroidism or hypothyroidism. Patients with vitiligo or asthma (in childhood) which was completely resolved and without need of any intervention in adulthood can be included. However, subjects with asthma which needs bronchodilator for medical intervention cannot be included);
  11. Previous treatments with 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);
  12. Subjects diagnosed with active tuberculosis (TB), who are receiving anti-tuberculosis therapy or used to have anti-tuberculosis therapy within 1 year prior to screening;
  13. Concomitant diseases requiring long-term treatment with immunosuppressive drugs, or corticosteroids at an effective immunosuppressive dose (Prednisone at a dose of > 10 mg/day or other equivalent hormone formulations) for systemic or local treatment purpose;
  14. Subjects who have received any anti-infection vaccine (e.g. influenza vaccine, varicella vaccine, etc.) within 4 weeks prior to enrollment;
  15. Pregnant or lactating women
  16. Positive test for HIV;
  17. Positive test for HBsAg, with HBV DNA copies detected as positive (quantitative measurements ≥ 1000 cps/mL);
  18. Positive test for chronic Hepatitis C in blood screening test (HCV antibody positive); Any other clinical significant disease or condition, which as evaluated by the investigator, may affect the protocol compliance, signing of inform consent form (ICF), 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


Locations
Show Show 23 study locations
Sponsors and Collaborators
Shanghai Junshi Bioscience Co., Ltd.
Investigators
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Principal Investigator: Ruihua Xu, MD, PhD Sun Yat-sen University
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: NCT02915432    
Other Study ID Numbers: JS001-Ib-CRP-1.0
First Posted: September 27, 2016    Key Record Dates
Last Update Posted: October 23, 2019
Last Verified: October 2019
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:
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Carcinoma
Carcinoma, Squamous Cell
Adenocarcinoma
Nasopharyngeal Carcinoma
Squamous Cell Carcinoma of Head and Neck
Esophageal Squamous Cell Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell
Nasopharyngeal Neoplasms
Pharyngeal Neoplasms
Otorhinolaryngologic Neoplasms
Head and Neck Neoplasms
Neoplasms by Site
Nasopharyngeal Diseases
Pharyngeal Diseases
Stomatognathic Diseases
Otorhinolaryngologic Diseases
Esophageal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Esophageal Diseases
Gastrointestinal Diseases