Toripalimab or Placebo With Paclitaxel and Cisplatin in Esophageal Squamous Cell Carcinoma

Inclusion Criteria： Inclusion criteria for oesophageal cancer Histologically or cytologically diagnosed locally advanced / recurrent or metastatic ESCC without radical treatment; No prior systemic anti-tumor therapy for recurrent or metastatic tumor. No recurrence at least 6 months from the end of last treatment in the patients previously receiving adjuvant, neoadjuvant chemotherapy/radiotherapy/chemoradiotherapy and radical therapy for non-metastatic disease (No recurrence at least 12 months from the end of last treatment in the patients previously receiving adjuvant chemotherapy/chemoradiotherapy with TP regimen); No risk of major hemorrhage or esophageal fistula, for example, large ulcer at the lesion is considered as the risk for major hemorrhage and esophageal fistula, the patient is not suitable to be enrolled. Subjects with tumor directly invading adjacent organs such as the aorta or trachea (T4b disease) should be closely assessed for risk of hemorrhage or fistula and consult the sponsor prior to enrollment.

General requirements for inclusion:

Signed informed consent; Male or female aged 18 to 70 years ECOG score 0 or 1; Expected survival longer than 3 months; Agreement upon providing previously reserved tumor tissue specimen or biopsied tumor lesion tissue for biomarker analysis.

At least one measurable lesion in accordance with RECIST 1.1 (only when clear progression of disease occurs after radiotherapy for the previously irradiated lesion, the lesion can be used as measurable lesion).

Good organ function level:

Hematology: neutrophil ≥1.5×10^9/L, hemoglobin ≥9 g/dL and platelet ≥100×10^9/L.

Hepatic function: bilirubin ≤1.5 time of upper limit of normal (ULN) (patients who are known to have Gilbert disease and serum bilirubin level ≤3 times of ULN can be enrolled), AST and ALT ≤2.5 times of ULN (in case of hepatic metastasis, AST /ALT≤5 times of ULN), and alkaline phosphatase≤3 times of ULN (in case of hepatic or bone metastasis, ALP≤5 times of ULN); albumin ≥3g / dL; International normalized ratio (INR) or prothrombin time (PT) or activated partial thromboplastin time (aPTT) ≤1.5 x ULN.

Renal function: serum creatinine ≤1.5 × ULN or estimated glomerular filtration rate in accordance with Cockcroft-Gault formula: creatinine clearance ≥60 mL/min ((140 - age)x(weight，kg)x(0.85，for women))/(72 x(serum creatinine，mg/dL))

Or:

((140 - age)x(weight，kg)x(0.85，for women))/(0.818 x(serum creatinine，μmol/L))

Women who meet the following criteria are eligible to be included and participate in the study:

No childbearing potential (e.g., physiologically infertile), women meeting any one of the following conditions:

Having undergone uterectomy, Having undergone bilateral oophorectomy (oophorectomy), Having undergone ligation of bilateral fallopian tubes, or Postmenopause (total duration of menopause ≥1 year).

Having childbearing potential, serum pregnancy test negative at screening (within 7 days prior to the first dose of study drug), and adequate contraceptive measures taken prior to entry in the study and throughout the study, until 60 days after the last dose of the study drug. The adequate contraceptive measure taken continuously in accordance with the instruction on the contraceptive product and physician's guidance is defined as below:

Any intrauterine device confirmed to have a failure rate for contraception less than 1% per year Dual barrier contraception is defined as the condom with spermicidal gel, foam, suppository or film; or diaphragma with spermicide; or male condom and diaphragma.

Exclusion Criteria

Cancer-specific exclusion criteria:

Active or untreated CNS metastasis determined through CT or magnetic resonance imaging (MRI) evaluation in screening period and previous radiological evaluation (e.g., brain or leptomeningeal metastasis). Patients who have received previous treatment of brain or meningeal metastases, who have been stabilized for at least 2 months and discontinued systemic hormone ther