TQB2450 Solution for Injection (TQB2450)+Paclitaxel+Cisplatin ± Anlotinib in the Treatment of Esophageal Cancer.

Study Overview
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Brief Summary
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The regimen of paclitaxel+cisplatin+TQB2450 injection combined or not combined with anlotinib is the first-line treatment of advanced esophageal squamous cell carcinoma. Take PFS as the main evaluation index, the purpose is to evaluate its effectiveness and safety

Official Title
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A Multicenter Exploratory Study of Paclitaxel+Cisplatin+TQB2450 Injection Combined With or Without Anlotinib in the First-line Treatment of Advanced Esophageal Squamous Cell Carcinoma

Conditions
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Esophageal Neoplasms

Intervention / Treatment
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* Drug: Paclitaxel + Cisplatin + TQB2450 injection+ Anlotinib
* Drug: Paclitaxel + Cisplatin + TQB2450 injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically confirmed squamous cell carcinoma of the esophagus, locally advanced, unresectable, recurrent or metastatic disease. Those who have not received systemic treatment before, or who relapsed after (new) adjuvant therapy/radical surgery more than 6 months ; Note: Including advanced or recurrent Patients who ever received only radiotherapy on non-target lesions. The duration from the end of palliative treatment for local lesions (non-target lesions) to enrollment should > 2 weeks; According to RECIST 1.1, at least one measurable lesion; the measurable lesions should not have received local treatment such as radiotherapy (for the lesions in the area where received local radiotherapy, it can also be regarded as a target lesion if confirmed to progress according to the recist1.1); 18 and 75 years old; Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1；Life expectancy of at least 3 months. the main organ function to meet the following criteria: (1)Blood routine tests met the following requirements: a) haemoglobin(HB)≥90g/L ； b) absolute neutrophil count(NEUT)≥1.5×109/L ； c) platelet count(PLT)≥100×109/L； （2） Biochemical tests met the following requirements： total bilirubin(TBIL)≤ 1.5 times the upper limit of normal (ULN) .≤5 × ULN if with liver involvement； serum creatinine ≤1.5 × the ULN or creatinine clearance≥50mL/min。 （3） Coagulation or thyroid function meet the following criteria: International Normalized Ratio (INR) ≤1.5 and Partial Thromboplastin Time (PT) or activated PTT (APTT) ≤1.5 × (ULN)). Male or female subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 3 months after the last dose of study The patient volunteers to participate in the study, signs a consent form, has good compliance, and obeys the follow-up, and is willing and able to follow the protocol during the study. Exclusion Criteria: Patients tends to have complete obstruction or patients requiring interventional treatment for obstruction; Patients with a high risk of bleeding or perforation due to the apparent invasion of adjacent organs (aorta or trachea) of the esophageal lesion, or patients who have formed fistulas; Patients with symptoms of hematemesis, hematochezia and daily bleeding ≥ 2.5 mL, or any bleeding event with Common Terminology Criteria for Adverse Events （CTCAE） level 3 within 3 months before screening; allergic to study drugs 、paclitaxel and cisplatin preparations or excipients; Adjuvant chemotherapy patients who have used paclitaxel or cisplatin, and relapse or metastasize within one year A variety of factors affecting oral medications (such as inability to swallow, chronic diarrhea, and intestinal obstruction); patients with any severe and / or uncontrolled disease, including:Unsatisfactory blood pressure control using antihypertensive drugs (systolic blood pressure ≥150 mmhg or diastolic blood pressure ≥100) Mmhg) patients; patients with grade ≥ myocardial ischemia or myocardial infarction, arrhythmia (including qt interval ≥ 480ms); according to nyha criteria, iii-iv cardiac dysfunction, or cardiac ultrasonography prompted left ventricular ejection fraction (lvef) <50% of patients;live Severe infection that is sexual or uncontrolled;Liver diseases such as cirrhosis, decompensated liver disease, chronic active hepatitis;poor diabetes control (fasting blood glucose (fbg)>10mmol/l);Urine routine indicates that urine protein ≥ ++, and confirmed 24-hour urine protein quantitation > 1.0 g long-term unhealed wounds or fractures; Patients with active hemorrhage within 2 months of primary lesions; pulmonary hemorrhage with NCI CTCAE grade >1, 4 weeks before of enrollment; other sites of bleeding NCI CTCAE grade >2, 4 weeks before of enrollment; patients with bleeding tendency (such as active gastrointestinal ulcers) or patients undergoing thrombolytic or anticoagulant therapy such as warfarin, heparin or its analogues; Have undergone major surgery (craniotomy, thoracotomy or open surgery) within 4 weeks prior to the first dose study or Major surgery is required during the study period. A history of gastrointestinal perforation and/or fistula occurred within 6 months prior to treatment; or an overactive/venous thrombosis event such as a cerebrovascular accident (including transient ischemic attack), deep vein thrombosis, and lung Embolism； Symptomatic central nervous system metastasis and/or cancerous meningitis are known to exist; Clinically significant ascites, including any ascites that can be found on a physical examination, ascites that has been treated or currently in need of treatment, and only those with a small amount of ascites but no symptoms can be selected; A moderate amount of fluid in both sides of the chest, or a large amount of fluid in one side of the chest, or has caused respiratory dysfunction Patient to be drained; known to have active tuberculosis; suffering from interstitial lung disease requiring steroid therapy; Uncontrolled metabolic disorders or other non-malignant tumors or systemic diseases or cancer secondary reactions that can lead to higher medical risks and/or survival Evaluation of uncertainty; Significantly malnourished patients; those who have a history of psychotropic substance abuse and are unable to quit or have a mental disorder; A history of immunodeficiency, including a positive HIV test or other acquired, congenital immunodeficiency disease, or a history of organ transplantation; History of other primary malignancies, but the following : 1) complete remission of malignant tumors for at least 2 years prior to enrollment and no additional treatment during the study; 2) non-melanoma skin cancer or malignant freckle-like sputum with adequate treatment and no evidence of disease recurrence; 3) adequately treated and In situ carcinoma without evidence of disease recurrence; Female patients who are pregnant or breastfeeding; According to the judgment of the investigator, there is a concomitant disease that seriously endangers the safety of the patient or affects the completion of the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental group 1<br>Initial treatment: Paclitaxel + Cisplatin + TQB2450 injection+ Anlotinib (4-6 cycles). Maintenance treatment: TQB2450 injection+Anlotinib. | Drug: Paclitaxel + Cisplatin + TQB2450 injection+ Anlotinib<br>* TQB2450 injection: 1200 mg, i.v.gtt , d1;Anlotinib 10mg, po.qd , d1-14；Paclitaxel 135mg/m2, i.v.gtt , d1; Cisplatin 60-75mg/m2, i.v.gtt , d1-d3; The above schemes are repeated every three weeks. After 4-6 cycles, the regimen is changed to Anlotinib (10mg, po.qd , d1-14)+TQB2450 injection（1200 mg, i.v.gtt , d1）. The regimen is repeated every 3 weeks until the disease progresses.<br>|
| Experimental: Experimental group 2<br>Initial treatment: Paclitaxel + Cisplatin + TQB2450 injection (4-6 cycles). Maintenance treatment: TQB2450 injection. | Drug: Paclitaxel + Cisplatin + TQB2450 injection<br>* TQB2450 injection: 1200 mg, i.v.gtt , d1;Paclitaxel 135mg/m2, i.v.gtt , d1; Cisplatin 60-75mg/m2, i.v.gtt , d1-d3; The above schemes are repeated every three weeks. After 4-6 cycles, the regimen is changed to TQB2450 injection（1200 mg, i.v.gtt , d1）. The regimen is repeated every 3 weeks until the disease progresses.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression free survival (PFS， RECIST assessment) |  | each 42 days（Initial treatment） or 63 days ( Maintenance treatment) up to Progressive Disease or Intolerable toxicity （Up to 24 months） | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival (iPFS) |  | each 42 days（Initial treatment） or 63 days ( Maintenance treatment) up to Progressive Disease or Intolerable toxicity （Up to 24 months） | 
| Objective response rate (ORR) |  | each 42 days（Initial treatment） or 63 days ( Maintenance treatment) up to Progressive Disease or Intolerable toxicity （Up to 24 months） | 
| Disease control rate (DCR） |  | each 42 days（Initial treatment） or 63 days ( Maintenance treatment) up to Progressive Disease or Intolerable toxicity （Up to 24 months） | 
| Duration of response (DOR) |  | each 42 days（Initial treatment） or 63 days ( Maintenance treatment) up to Progressive Disease or Intolerable toxicity （Up to 24 months） | 
| Incidence of Treatment-related adverse Events |  | Through study completion, an average of 3 weeks |