<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03829969</url>
  </required_header>
  <id_info>
    <org_study_id>JS001-021-III-ESCC</org_study_id>
    <nct_id>NCT03829969</nct_id>
  </id_info>
  <brief_title>Toripalimab or Placebo With Paclitaxel and Cisplatin in Esophageal Squamous Cell Carcinoma</brief_title>
  <acronym>JUPITER06</acronym>
  <official_title>A Phase III, Randomized, Double-blind, Placebo-controlled, Multi-center Study to Compare Toripalimab Injection (JS001) Combined With Standard Chemotherapy Versus Placebo Combined With Standard Chemotherapy in Treatment of Advanced or Metastatic Esophageal Squamous Cell Cancer (ESCC) Without Previous Systemic Chemotherapy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Shanghai Junshi Bioscience Co., Ltd.</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Shanghai Junshi Bioscience Co., Ltd.</source>
  <oversight_info>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is one randomized, double-blind, multi-center, placebo-controlled phase III study. The&#xD;
      objective of this study is to compare the effectiveness and safety of JS001 combined with&#xD;
      paclitaxel and cisplatin(TP regimen )with placebo combined with TP regimen in patients with&#xD;
      advanced or metastatic Esophageal Squamous Cell Carcinoma(ESCC )who have not received&#xD;
      systemic chemotherapy previously.&#xD;
&#xD;
      About 500 patients with advanced or metastatic ESCC who have not received chemotherapy&#xD;
      previously will be enrolled in this study and 1:1 randomized into JS001 combined with TP&#xD;
      group and placebo combined with TP group (i.e., 250 patients each in group A and B) The&#xD;
      sample size was calculated based on the dual-endpoint of primary effectiveness endpoint&#xD;
      (progression-free survival, PFS, as evaluated by BIRC per RECIST v1.1 criteria) and overall&#xD;
      survival (OS). The hierarchical testing will be used for PFS and OS analysis at the overall&#xD;
      significance level of two-sided 0.05, that is, all α levels (two-sided 0.05) will be firstly&#xD;
      used for the hypothesis test of PFS; if the null hypothesis of PFS is rejected, the&#xD;
      hypothesis test of OS will be performed at the two-sided significance level of 0.05. For PFS,&#xD;
      it will be expected to observe 283 PFS events in 500 patients enrolled about 24 months after&#xD;
      randomization of the first subject, thereby there is 85% statistical power to detect an&#xD;
      improved PFS for JS001 in combination with TP versus placebo in combination with TP in&#xD;
      subject with advanced or metastatic ESCC who had not previously received chemotherapy at the&#xD;
      two-sided significance level of 0.05 (corresponding hazard ratio (HR) =0.7); for OS, it will&#xD;
      be expected to observe 366 OS events in 500 patients enrolled about 39 months after&#xD;
      randomization of the first subject, thereby there is 85% statistical power to detect an&#xD;
      improved OS for JS001 in combination with TP versus placebo in combination with TP in subject&#xD;
      with advanced or metastatic ESCC who had not previously received chemotherapy at the&#xD;
      two-sided significance level of 0.05 (corresponding hazard ratio (HR) =0.73). It is planned&#xD;
      to performed an interim analysis of OS at the time of PFS analysis (about 24 months after&#xD;
      randomization of the first subject).&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">January 31, 2019</start_date>
  <completion_date type="Anticipated">February 28, 2022</completion_date>
  <primary_completion_date type="Actual">March 22, 2021</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>PFS</measure>
    <time_frame>PFS, defined as the time from randomization to the first progression of disease, or the time from randomization to death for any reason, whichever comes first, will be determined by blind independent centre review (BICR) in accordance with RECIST 1.1</time_frame>
    <description>To evaluate the differences in PFS following JS001 in combination with TP regimen compared to placebo in combination with TP regimen in all randomized patient population with advanced or metastatic ESCC who had not previously received systemic chemotherapy (as assessed by blinded independent central review [BICR] per RECIST 1.1 criteria).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>OS</measure>
    <time_frame>OS is defined as the time from randomization to death for any cause.</time_frame>
    <description>To evaluate the differences in OS following JS001 in combination with TP regimen compared to placebo in combination with TP regimen in all randomized patient population with advanced or metastatic ESCC who had not previously received systemic chemotherapy (as assessed by blinded independent central review [BICR] per RECIST 1.1 criteria)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>ORR(overall response rate)</measure>
    <time_frame>Up to 2 approximately years</time_frame>
    <description>To evaluate the efficacy of JS001 plus chemotherapy compared with placebo plus chemotherapy, as measured by blind independent review committee BIRC and investigator-assessed overall response rate (ORR), daccording to RECIST v1.1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>DCR(disease control rate )</measure>
    <time_frame>Up to 2 approximately years</time_frame>
    <description>To evaluate the efficacy of JS001 plus chemotherapy compared with placebo plus chemotherapy, as measured by blind independent review committee BIRC and investigator-assessed disease control rate (DCR) according to RECIST v1.1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>DOR(duration of response )</measure>
    <time_frame>Up to 2 approximately years</time_frame>
    <description>To evaluate the efficacy of JS001 plus chemotherapy compared with placebo plus chemotherapy, as measured by blind independent review committee BIRC and investigator-assessed duration of response (DoR) according to RECIST v1.1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>TTR(Time to initial Response )</measure>
    <time_frame>Up to 2 approximately years</time_frame>
    <description>To evaluate the efficacy of JS001 plus chemotherapy compared with placebo plus chemotherapy, as measured by blind independent review committee BIRC and investigator-assessed Time to initial Response (TTR) according to RECIST v1.1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PFS</measure>
    <time_frame>Up to 2 approximately years</time_frame>
    <description>To evaluate the efficacy of JS001 plus chemotherapy compared with placebo plus chemotherapy，as measured by investigator-assessed progression free survival (PFS) according to RECIST v1.1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PFS rate</measure>
    <time_frame>Up to 2 approximately years</time_frame>
    <description>To evaluate the PFS rate at 1 and 2 years</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>OS rate</measure>
    <time_frame>Up to 33 months</time_frame>
    <description>To evaluate the OS rate at 1 and 2 years</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PFS assessed per irRECIST</measure>
    <time_frame>From date of randomization, until disease progression , loss of clinical benefit ,withdrawal of consent, death, or study termination by the Sponsor, whichever occurs first. Up to 2 approximately years</time_frame>
    <description>To evaluate PFS of JS001 plus chemotherapy compared with placebo plus chemotherapy according to irRECIST</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>ORR assessed per irRECIST</measure>
    <time_frame>From date of randomization, until disease progression , loss of clinical benefit ,withdrawal of consent, death, or study termination by the Sponsor, whichever occurs first. Up to 2 approximately years</time_frame>
    <description>To evaluate ORR of JS001 plus chemotherapy compared with placebo plus chemotherapy according to irRECIST</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>DoR assessed per irRECIST</measure>
    <time_frame>From date of response until progressive disease. Up to 2 approximately years</time_frame>
    <description>To evaluate DOR of JS001 plus chemotherapy compared with placebo plus chemotherapy according to irRECIST</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>DCR assessed per irRECIST</measure>
    <time_frame>From date of randomization, until disease progression , loss of clinical benefit ,withdrawal of consent, death, or study termination by the Sponsor, whichever occurs first. Up to 2 approximately years</time_frame>
    <description>To evaluate DCR of JS001 plus chemotherapy compared with placebo plus chemotherapy according to irRECIST</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>TTR assessed per irRECIST</measure>
    <time_frame>From date of randomization, until disease progression , loss of clinical benefit ,withdrawal of consent, death, or study termination by the Sponsor, whichever occurs first. Up to 2 approximately years</time_frame>
    <description>To evaluate TTR of JS001 plus chemotherapy compared with placebo plus chemotherapy according to irRECIST</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient-Reported Outcomes collected via the EORTC QLQ-C30</measure>
    <time_frame>From date of randomization, until disease progression , loss of clinical benefit ,withdrawal of consent, death, or study termination by the Sponsor, whichever occurs first. Up to 2 approximately years</time_frame>
    <description>To evaluate the quality of life (QoL) following JS001 in combination with TP regimen compared to placebo in combination with TP regimen in all randomized population.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient-Reported Outcomes collected via the EORTC QLQ-OES18</measure>
    <time_frame>From date of randomization, until disease progression , loss of clinical benefit ,withdrawal of consent, death, or study termination by the Sponsor, whichever occurs first. Up to 2 approximately years</time_frame>
    <description>To evaluate the quality of life (QoL) following JS001 in combination with TP regimen compared to placebo in combination with TP regimen in all randomized population.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">514</enrollment>
  <condition>Advanced or Metastatic Esophageal Squamous Cell Cancer Without Previous Systemic Chemotherapy</condition>
  <arm_group>
    <arm_group_label>Toripalimab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Toripalimab combine with paclitaxel and cisplatin</description>
  </arm_group>
  <arm_group>
    <arm_group_label>placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo combine with paclitaxel and cisplatin</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Toripalimab</intervention_name>
    <description>TORIPALIMAB INJECTION(JS001 ) combine with chemotherapy or placebo combine with chemotherapy</description>
    <arm_group_label>Toripalimab</arm_group_label>
    <arm_group_label>placebo</arm_group_label>
    <other_name>JS001, TAB001</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria： Inclusion criteria for oesophageal cancer Histologically or&#xD;
        cytologically diagnosed locally advanced / recurrent or metastatic ESCC without radical&#xD;
        treatment; No prior systemic anti-tumor therapy for recurrent or metastatic tumor. No&#xD;
        recurrence at least 6 months from the end of last treatment in the patients previously&#xD;
        receiving adjuvant, neoadjuvant chemotherapy/radiotherapy/chemoradiotherapy and radical&#xD;
        therapy for non-metastatic disease (No recurrence at least 12 months from the end of last&#xD;
        treatment in the patients previously receiving adjuvant chemotherapy/chemoradiotherapy with&#xD;
        TP regimen); No risk of major hemorrhage or esophageal fistula, for example, large ulcer at&#xD;
        the lesion is considered as the risk for major hemorrhage and esophageal fistula, the&#xD;
        patient is not suitable to be enrolled. Subjects with tumor directly invading adjacent&#xD;
        organs such as the aorta or trachea (T4b disease) should be closely assessed for risk of&#xD;
        hemorrhage or fistula and consult the sponsor prior to enrollment.&#xD;
&#xD;
        General requirements for inclusion:&#xD;
&#xD;
        Signed informed consent; Male or female aged 18 to 70 years ECOG score 0 or 1; Expected&#xD;
        survival longer than 3 months; Agreement upon providing previously reserved tumor tissue&#xD;
        specimen or biopsied tumor lesion tissue for biomarker analysis.&#xD;
&#xD;
        At least one measurable lesion in accordance with RECIST 1.1 (only when clear progression&#xD;
        of disease occurs after radiotherapy for the previously irradiated lesion, the lesion can&#xD;
        be used as measurable lesion).&#xD;
&#xD;
        Good organ function level:&#xD;
&#xD;
        Hematology: neutrophil ≥1.5×10^9/L, hemoglobin ≥9 g/dL and platelet ≥100×10^9/L.&#xD;
&#xD;
        Hepatic function: bilirubin ≤1.5 time of upper limit of normal (ULN) (patients who are&#xD;
        known to have Gilbert disease and serum bilirubin level ≤3 times of ULN can be enrolled),&#xD;
        AST and ALT ≤2.5 times of ULN (in case of hepatic metastasis, AST /ALT≤5 times of ULN), and&#xD;
        alkaline phosphatase≤3 times of ULN (in case of hepatic or bone metastasis, ALP≤5 times of&#xD;
        ULN); albumin ≥3g / dL; International normalized ratio (INR) or prothrombin time (PT) or&#xD;
        activated partial thromboplastin time (aPTT) ≤1.5 x ULN.&#xD;
&#xD;
        Renal function: serum creatinine ≤1.5 × ULN or estimated glomerular filtration rate in&#xD;
        accordance with Cockcroft-Gault formula: creatinine clearance ≥60 mL/min ((140 -&#xD;
        age)x(weight，kg)x(0.85，for women))/(72 x(serum creatinine，mg/dL))&#xD;
&#xD;
        Or:&#xD;
&#xD;
        ((140 - age)x(weight，kg)x(0.85，for women))/(0.818 x(serum creatinine，μmol/L))&#xD;
&#xD;
        Women who meet the following criteria are eligible to be included and participate in the&#xD;
        study:&#xD;
&#xD;
        No childbearing potential (e.g., physiologically infertile), women meeting any one of the&#xD;
        following conditions:&#xD;
&#xD;
        Having undergone uterectomy, Having undergone bilateral oophorectomy (oophorectomy), Having&#xD;
        undergone ligation of bilateral fallopian tubes, or Postmenopause (total duration of&#xD;
        menopause ≥1 year).&#xD;
&#xD;
        Having childbearing potential, serum pregnancy test negative at screening (within 7 days&#xD;
        prior to the first dose of study drug), and adequate contraceptive measures taken prior to&#xD;
        entry in the study and throughout the study, until 60 days after the last dose of the study&#xD;
        drug. The adequate contraceptive measure taken continuously in accordance with the&#xD;
        instruction on the contraceptive product and physician's guidance is defined as below:&#xD;
&#xD;
        Any intrauterine device confirmed to have a failure rate for contraception less than 1% per&#xD;
        year Dual barrier contraception is defined as the condom with spermicidal gel, foam,&#xD;
        suppository or film; or diaphragma with spermicide; or male condom and diaphragma.&#xD;
&#xD;
        Exclusion Criteria&#xD;
&#xD;
        Cancer-specific exclusion criteria:&#xD;
&#xD;
        Active or untreated CNS metastasis determined through CT or magnetic resonance imaging&#xD;
        (MRI) evaluation in screening period and previous radiological evaluation (e.g., brain or&#xD;
        leptomeningeal metastasis). Patients who have received previous treatment of brain or&#xD;
        meningeal metastases, who have been stabilized for at least 2 months and discontinued&#xD;
        systemic hormone therapy (&gt; 10 mg/d of prednisone or equivalent) for &gt; 4 weeks prior to&#xD;
        randomization; Uncontrolled tumor related pain; Uncontrolled pleural effusion, pericardial&#xD;
        effusion, or ascites requiring repeated drainage (once per month or more frequent);&#xD;
        indewlling catheter (e.g. PleurX®) is allowed; Uncontrollable or symptomatic hypercalcemia&#xD;
        (ionized calcium&gt;1.5 mmol/L or calcium &gt;12 mg/dL or corrected serum calcium &gt;ULN); History&#xD;
        of malignant tumors except esophageal cancer within 5 years prior to randomization, but&#xD;
        except the malignant tumors that risk of metastasis or death can be neglected [e.g.,&#xD;
        expected 5-year survival rate&gt; 90%], and are expected to be cured after treatment, for&#xD;
        example, appropriately treated carcinoma in situ of cervix, basal or squamous cell skin&#xD;
        cancer, local prostate cancer treated with radical operation, and ductal carcinoma in situ&#xD;
        treated with radical operation; Palliative Radiotherapy within 4 weeks prior to enrollment,&#xD;
        or radiopharmaceutical therapy within 8 weeks, however, except locally palliative&#xD;
        radiotherapy for bone metastatic lesions; in case of symptomatic lesion suitable for&#xD;
        palliative chemotherapy, the therapy should be given prior to enrollment. The effect of&#xD;
        previous radiotherapy has been recovered. The shortest recovery period is not required;&#xD;
        Subjects with bone metastases of multiple vertebra are prone to fractures and may cause&#xD;
        risk of paraplegia, except for Subjects who are assessed as stable and do not need to be&#xD;
        treated for the time being evaluated by a specialist.&#xD;
&#xD;
        Subjects with advanced tumors spreading to vital organs and being in risk of developing&#xD;
        life-threatening complications in the short term ( eg. metastatic disease burden of liver ≥&#xD;
        50% of total liver volume).&#xD;
&#xD;
        Subjects with known complete obstruction under endoscopy requiring interventions or surgery&#xD;
        to remove obstruction and who have undergone tracheal or esophageal stenting; Subjects&#xD;
        whose BMI are less than 17.5, or body weight decrease &gt;10% within 2 months prior to first&#xD;
        dose of study treatment (considering changes of massive pleural effusion and ascites) or&#xD;
        with severe malnutrition as indicated by other indicators.&#xD;
&#xD;
        General medical exclusion criteria:&#xD;
&#xD;
        Women who are pregnant or lactating, or plan to be pregnant during the study; History of&#xD;
        serious allergic reaction, anaphylactoid or other hypersensitive reactions to chimeric or&#xD;
        humanized antibody or fusion protein; Known allergy or hypersensitivity to the biological&#xD;
        products manufactured from Chinese hamster ovary cells or any component of JS001&#xD;
        preparation; History of autoimmune disease, including but not limited to myasthenia gravis,&#xD;
        myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis,&#xD;
        inflammatory bowel disease, antiphospholipid syndrome-related vascular thrombosis,&#xD;
        Wegener's granulomatosis, Sjogren's syndrome, Guillain-Barre syndrome, multiple sclerosis,&#xD;
        vasculitis, glomerulonephritis; Patients with hypothyroidism who receive stable-dose&#xD;
        thyroid hormone replacement therapy can be enrolled in this study (the replacement therapy&#xD;
        for hypothyroidism is seen in Appendix 6); Patients with type I diabetes whose blood&#xD;
        glucose can be controlled through stable-dose insulin can be enrolled in this study;&#xD;
&#xD;
        Patients with eczema, psoriasis, chronic lichen simplex or only the dermatological&#xD;
        manifestations of vitiligo (e.g., patients with psoriatic arthritis will be excluded from&#xD;
        the study) are allowed to be enrolled in this study if they meet the following conditions:&#xD;
&#xD;
        The coverage area of rashes must be lower than 10% of body surface area (BSA); The disease&#xD;
        has been sufficiently controlled at baseline and only low-potency topical steroid therapy&#xD;
        is needed; No acute exacerbation of underlying diseases in the past 12 months [no need of&#xD;
        PUVA (Psoralen plus ultraviolet A radiation), methotrexate, retinol, biological&#xD;
        preparation, oral calcineurin inhibitor, high-potency or oral steroid therapy].&#xD;
&#xD;
        History of idiopathic pulmonary fibrosis, organized pneumonia (e.g., obliterative&#xD;
        bronchiolitis), drug induced pneumonia, idiopathic pneumonia interstitial pneumonia or&#xD;
        evidence of active pneumonia found during chest CT scanning for screening; Patients with&#xD;
        positive result of human immunodeficiency virus (HIV) test&#xD;
&#xD;
        Patients with hepatitis B (known positive HBV surface antigen HBsAg and HBV DNA ≥1000&#xD;
        cps/ml or 200 IU/ml or higher than upper limit of normal at each study site) or hepatitis&#xD;
        C:&#xD;
&#xD;
        Subjects with previous hepatitis B virus (HBV) infection can be included in this study.&#xD;
        Such subjects must undergo HBV deoxyribonucleic acid (DNA) testing prior to randomization,&#xD;
        and can participate in this study only when HBV DNA is negative (HBV DNA ˂1000 cps/mL or&#xD;
        200 IU/mL or below the upper limit of its normal value); In patients with positive&#xD;
        hepatitis C virus (HCV) antibody, only the patients with negative polymerase chain reaction&#xD;
        (PCR) HCV ribonucleic acid (RNA) can participate in this study.&#xD;
&#xD;
        Patients with active pulmonary tuberculosis (clinical diagnosis includes clinical history,&#xD;
        physical examination and radiological findings, as well as the TB test performed in&#xD;
        accordance with local medical routines); Serious infection within 4 weeks prior to&#xD;
        randomization, including but not limited to the infection complications, bacteremia and&#xD;
        severe pneumonia requiring hospitalization; Oral or intravenous antibiotics within two&#xD;
        weeks prior to randomization; patients receiving preventive antibiotic therapy (e.g., for&#xD;
        prevention of urinary tract infection or prevention of exacerbation of chronic obstructive&#xD;
        pulmonary disease) can be enrolled.&#xD;
&#xD;
        Important cardiovascular diseases, e.g., heart disease defined by New York Heart&#xD;
        Association (Grade II or above), myocardial infarction within three months prior to&#xD;
        randomization, unstable arrhythmia, unstable angina pectoris, cerebrovascular accident or&#xD;
        transient cerebral ischemic attack; patients with known coronary artery disease, congestive&#xD;
        heart failure not meeting the above criteria or left ventricular ejection fraction &lt; 50%&#xD;
        must receive the regimen that is considered by the attending physician as the optimal for&#xD;
        stabilizing therapy, and can consult a cardiologist when necessary; Major surgery (except&#xD;
        for diagnostic operation) within 28 weeks prior to randomization or expected major surgery&#xD;
        during the study; Previous allogeneic bone marrow transplantation or solid organ&#xD;
        transplantation. Use of attenuated live vaccine within 4 weeks prior to randomization, or&#xD;
        plan to use such attenuated live vaccine during the study Any other disease, metabolic&#xD;
        disorder, physical examination finding or abnormal laboratory examination, with the reason&#xD;
        to suspect that it can lead to contraindicated use of the investigational product, or&#xD;
        affect reliability of the study results, or place the patient at high risk;&#xD;
&#xD;
        Exclusion criteria related to medications:&#xD;
&#xD;
        Patients who have previously received any approved Chinese patent medicine as anti-tumor&#xD;
        indication within 2 weeks before first dose of study drug; Subjects treated with other&#xD;
        investigational product or participation in the clinical study for other therapeutic&#xD;
        objectives within 28 days prior to randomization (including signature of ICF for other&#xD;
        trials, and failure of screening); Previous use of immune checkpoint blocking therapy, for&#xD;
        example, anti-programmed death receptor -1 (anti-PD-1) and anti-PD-L1 antibody and other&#xD;
        therapeutic antibody; Use of systemic immunostimulator therapy [including but not limited&#xD;
        to interferon (IFN) or interleukin-2] within 2 weeks or 5 half-lives (t1/2) prior to&#xD;
        randomization, whichever comes later; vaccination of cancer vaccine is allowed in previous&#xD;
        treatment; Use of systemic immunosuppressive drugs (&gt;10 mg/d Prednisone or equivalent drug)&#xD;
        within two weeks prior to randomization, including but not limited to Prednisone,&#xD;
        Cyclophosphamide, azathioprine, methotrexate, thalidomide and tumor necrosis factor (TNF);&#xD;
        Patients who have received short-term, low-dose, systemic immunosuppressant (e.g., one&#xD;
        single dose of Dexamethasone for nausea) can participate in this study after discussion by&#xD;
        investigators and medical monitor and approval by medical monitor; Patients who use inhaled&#xD;
        corticosteroids for treatment of chronic obstructive pulmonary disease, mineralocorticoids&#xD;
        (e.g., fludrocortisone) for treatment of orthostatic hypotension and low-dose&#xD;
        glucocorticoid (≤10mg /d Prednisone or equivalent drug) supplement for treatment of&#xD;
        hypoadrenocorticism can be enrolled.&#xD;
&#xD;
        Patients who have previously received the hematopoietic growth factors (e.g. granulocyte&#xD;
        colony-stimulating factor (G-CSF) and erythropoietin) or blood transfusion within 2 week&#xD;
        before randomization.&#xD;
&#xD;
        Exclusion criteria related to chemotherapy:&#xD;
&#xD;
        History of allergy to cisplatin, carboplatin or other platinum-based compounds; Grade 2 or&#xD;
        above peripheral neuropathy in accordance with common terminology criteria for adverse&#xD;
        event (CTCAE) v5.0.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ruihua Xu, Prof</last_name>
    <role>Principal Investigator</role>
    <affiliation>Sun Yat-sen University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Sun Yat-Sen University Cancer Center</name>
      <address>
        <city>Guangzhou</city>
        <state>Guangdong</state>
        <zip>510060</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>August 2021</verification_date>
  <study_first_submitted>January 17, 2019</study_first_submitted>
  <study_first_submitted_qc>February 1, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 4, 2019</study_first_posted>
  <last_update_submitted>August 30, 2021</last_update_submitted>
  <last_update_submitted_qc>August 30, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">September 5, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Neoplasms, Squamous Cell</mesh_term>
    <mesh_term>Carcinoma, Squamous Cell</mesh_term>
    <mesh_term>Esophageal Squamous Cell Carcinoma</mesh_term>
  </condition_browse>
  <pending_results>
    <submitted>March 31, 2022</submitted>
    <returned>April 28, 2022</returned>
    <submitted>November 25, 2022</submitted>
    <returned>December 21, 2022</returned>
    <submitted>August 17, 2023</submitted>
    <returned>September 11, 2023</returned>
  </pending_results>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03829969
org study id: JS001-021-III-ESCC
nct id: NCT03829969
lead sponsor: 
is fda regulated drug: Yes
is fda regulated device: No
This is one randomized, double-blind, multi-center, placebo-controlled phase III study. The
      objective of this study is to compare the effectiveness and safety of JS001 combined with
      paclitaxel and cisplatin(TP regimen )with placebo combined with TP regimen in patients with
      advanced or metastatic Esophageal Squamous Cell Carcinoma(ESCC )who have not received
      systemic chemotherapy previously.

      About 500 patients with advanced or metastatic ESCC who have not received chemotherapy
      previously will be enrolled in this study and 1:1 randomized into JS001 combined with TP
      group and placebo combined with TP group (i.e., 250 patients each in group A and B) The
      sample size was calculated based on the dual-endpoint of primary effectiveness endpoint
      (progression-free survival, PFS, as evaluated by BIRC per RECIST v1.1 criteria) and overall
      survival (OS). The hierarchical testing will be used for PFS and OS analysis at the overall
      significance level of two-sided 0.05, that is, all α levels (two-sided 0.05) will be firstly
      used for the hypothesis test of PFS; if the null hypothesis of PFS is rejected, the
      hypothesis test of OS will be performed at the two-sided significance level of 0.05. For PFS,
      it will be expected to observe 283 PFS events in 500 patients enrolled about 24 months after
      randomization of the first subject, thereby there is 85% statistical power to detect an
      improved PFS for JS001 in combination with TP versus placebo in combination with TP in
      subject with advanced or metastatic ESCC who had not previously received chemotherapy at the
      two-sided significance level of 0.05 (corresponding hazard ratio (HR) =0.7); for OS, it will
      be expected to observe 366 OS events in 500 patients enrolled about 39 months after
      randomization of the first subject, thereby there is 85% statistical power to detect an
      improved OS for JS001 in combination with TP versus placebo in combination with TP in subject
      with advanced or metastatic ESCC who had not previously received chemotherapy at the
      two-sided significance level of 0.05 (corresponding hazard ratio (HR) =0.73). It is planned
      to performed an interim analysis of OS at the time of PFS analysis (about 24 months after
      randomization of the first subject).
allocation: Randomized
intervention model: Sequential Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: PFS
time frame: PFS, defined as the time from randomization to the first progression of disease, or the time from randomization to death for any reason, whichever comes first, will be determined by blind independent centre review (BICR) in accordance with RECIST 1.1
description: To evaluate the differences in PFS following JS001 in combination with TP regimen compared to placebo in combination with TP regimen in all randomized patient population with advanced or metastatic ESCC who had not previously received systemic chemotherapy (as assessed by blinded independent central review [BICR] per RECIST 1.1 criteria).
measure: OS
time frame: OS is defined as the time from randomization to death for any cause.
description: To evaluate the differences in OS following JS001 in combination with TP regimen compared to placebo in combination with TP regimen in all randomized patient population with advanced or metastatic ESCC who had not previously received systemic chemotherapy (as assessed by blinded independent central review [BICR] per RECIST 1.1 criteria)
measure: ORR(overall response rate)
time frame: Up to 2 approximately years
description: To evaluate the efficacy of JS001 plus chemotherapy compared with placebo plus chemotherapy, as measured by blind independent review committee BIRC and investigator-assessed overall response rate (ORR), daccording to RECIST v1.1
measure: DCR(disease control rate )
time frame: Up to 2 approximately years
description: To evaluate the efficacy of JS001 plus chemotherapy compared with placebo plus chemotherapy, as measured by blind independent review committee BIRC and investigator-assessed disease control rate (DCR) according to RECIST v1.1
measure: DOR(duration of response )
time frame: Up to 2 approximately years
description: To evaluate the efficacy of JS001 plus chemotherapy compared with placebo plus chemotherapy, as measured by blind independent review committee BIRC and investigator-assessed duration of response (DoR) according to RECIST v1.1
measure: TTR(Time to initial Response )
time frame: Up to 2 approximately years
description: To evaluate the efficacy of JS001 plus chemotherapy compared with placebo plus chemotherapy, as measured by blind independent review committee BIRC and investigator-assessed Time to initial Response (TTR) according to RECIST v1.1
measure: PFS
time frame: Up to 2 approximately years
description: To evaluate the efficacy of JS001 plus chemotherapy compared with placebo plus chemotherapy，as measured by investigator-assessed progression free survival (PFS) according to RECIST v1.1
measure: PFS rate
time frame: Up to 2 approximately years
description: To evaluate the PFS rate at 1 and 2 years
measure: OS rate
time frame: Up to 33 months
description: To evaluate the OS rate at 1 and 2 years
measure: PFS assessed per irRECIST
time frame: From date of randomization, until disease progression , loss of clinical benefit ,withdrawal of consent, death, or study termination by the Sponsor, whichever occurs first. Up to 2 approximately years
description: To evaluate PFS of JS001 plus chemotherapy compared with placebo plus chemotherapy according to irRECIST
measure: ORR assessed per irRECIST
time frame: From date of randomization, until disease progression , loss of clinical benefit ,withdrawal of consent, death, or study termination by the Sponsor, whichever occurs first. Up to 2 approximately years
description: To evaluate ORR of JS001 plus chemotherapy compared with placebo plus chemotherapy according to irRECIST
measure: DoR assessed per irRECIST
time frame: From date of response until progressive disease. Up to 2 approximately years
description: To evaluate DOR of JS001 plus chemotherapy compared with placebo plus chemotherapy according to irRECIST
measure: DCR assessed per irRECIST
time frame: From date of randomization, until disease progression , loss of clinical benefit ,withdrawal of consent, death, or study termination by the Sponsor, whichever occurs first. Up to 2 approximately years
description: To evaluate DCR of JS001 plus chemotherapy compared with placebo plus chemotherapy according to irRECIST
measure: TTR assessed per irRECIST
time frame: From date of randomization, until disease progression , loss of clinical benefit ,withdrawal of consent, death, or study termination by the Sponsor, whichever occurs first. Up to 2 approximately years
description: To evaluate TTR of JS001 plus chemotherapy compared with placebo plus chemotherapy according to irRECIST
measure: Patient-Reported Outcomes collected via the EORTC QLQ-C30
time frame: From date of randomization, until disease progression , loss of clinical benefit ,withdrawal of consent, death, or study termination by the Sponsor, whichever occurs first. Up to 2 approximately years
description: To evaluate the quality of life (QoL) following JS001 in combination with TP regimen compared to placebo in combination with TP regimen in all randomized population.
measure: Patient-Reported Outcomes collected via the EORTC QLQ-OES18
time frame: From date of randomization, until disease progression , loss of clinical benefit ,withdrawal of consent, death, or study termination by the Sponsor, whichever occurs first. Up to 2 approximately years
description: To evaluate the quality of life (QoL) following JS001 in combination with TP regimen compared to placebo in combination with TP regimen in all randomized population.
arm group label: Toripalimab
arm group type: Experimental
description: Toripalimab combine with paclitaxel and cisplatin
arm group label: placebo
arm group type: Placebo Comparator
description: Placebo combine with paclitaxel and cisplatin
intervention type: Biological
intervention name: Toripalimab
description: TORIPALIMAB INJECTION(JS001 ) combine with chemotherapy or placebo combine with chemotherapy
arm group label: Toripalimab
arm group label: placebo
other name: JS001, TAB001
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Ruihua Xu, Prof
role: Principal Investigator
affiliation: Sun Yat-sen University
facility: 
country: China
responsible party type: Sponsor
mesh term: Neoplasms, Squamous Cell
mesh term: Carcinoma, Squamous Cell
mesh term: Esophageal Squamous Cell Carcinoma
submitted: March 31, 2022
returned: April 28, 2022
submitted: November 25, 2022
returned: December 21, 2022
submitted: August 17, 2023
returned: September 11, 2023