A Study of Anti-PD-L1 Antibody in Neoadjuvant Chemotherapy of Esophageal Squamous Cell Carcinoma.

Study Overview
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Brief Summary
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This is a randomized, double-blind, placebo-controlled Ib/Ⅱ clinical study to evaluate the safety and effect of anti-PD-L1 antibody (ZKAB001) in neoadjuvant chemotherapy of esophageal squamous carcinoma in combination with Alb-paclitaxel and cisplatin. The immunotherapy will be given before and after the operation every three weeks.

Official Title
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A Randomized, Double-blind, Placebo-controlled Phase Ib/II Clinical Study of Anti-pd-l1 Monoclonal Antibody Injection (ZKAB001) Combined Albumin Binding Paclitaxel, Cisplatin in Neoadjuvant Treatment of Esophageal Squamous Cell Carcinoma.

Conditions
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Esophageal Cancer

Intervention / Treatment
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* Drug: anti-PD-L1 antibody
* Drug: albumin bound paclitaxel
* Drug: cisplatin
* Drug: placebo
* Procedure: radical resection of esophageal carcinoma


Participation Criteria
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Eligibility Criteria
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Key inclusion Criteria: Aged 18 to 75 years old of either gender; A histopathological diagnosis of esophageal squamous cell carcinoma with a clinical stage of T2N+M0 or T3-4aN+/-M0 according to the 8th edition of the UICC staging system; ECOG score 0-1; Estimated life expectancy >3 months; BMI ≥18.5kg/m2 or PG-SGA score A/B; The function of important organs meets the following requirements: white blood cell count (WBC) ≥ 3.0×109/L, absolute neutrophil count (ANC) ≥ 1.5×109/L, platelets ≥ 100×109/L, hemoglobin ≥ 90g/L; ALT, AST and AKP ≤ 2.5×ULN; serum albumin ≥ 30g/L; total bilirubin ≤ 1.5×ULN; serum creatinine ≤ 1.0×ULN, creatinine clearance rate ≥60 mL/min; INR ≤ 1.5, PT≤ 1.5×ULN; Cardiac function: ≤I, pulmonary function: FEV1 >1.2L, FEV1% >40%, liver function: Child-Pugh 5-6; Serum HCG negative in premenopausal women ; Ability to understand the study and sign informed consent. Key exclusion Criteria: Cervical esophageal carcinoma; Patients who have been treated previously with anti-tumor therapy (including chemotherapy, radiotherapy, surgery, immunotherapy, etc.); Known or suspected allergy or hypersensitivity to monoclonal antibodies, any ingredients of anti-PD-L1 antibody and chemotherapeutic drugs; Active autoimmune diseases; A history of allogeneic stem cell transplantation and organ transplantation; A history of interstitial lung disease or non-infectious pneumonia; Patients who cannot tolerate chemotherapy or surgery due to severe cardiac, lung, liver or kidney dysfunction, or hematopoietic disease or cachexia; A history of immunodeficiency (including a positive HIV test result), or other acquired or congenital immunodeficiency diseases; Presence of active hepatitis B (HBV DNA ≥ 200 IU/mL or 103 copies/mL), hepatitis C (positive for hepatitis C antibody, and HCV-RNA levels higher than the lower limit of the assay); A history of active pulmonary tuberculosis infection within 1 year or a history of active pulmonary tuberculosis infection more than 1 year ago but without formal anti-tuberculosis treatment; A history of malignancies other than esophageal cancer before enrollment, excluding non-melanoma skin cancer, in situ cervical cancer, or cured early prostate cancer; Lymph node metastasis in neck, supraclavicular, abdominal cavity, retroperitoneum and pelvic cavity (except paracardial and left gastric lymph nodes).

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: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PD-L1 group<br>All patients will receive 16 cycles of anti-PD-L1 antibody (5mg/kg, IV, every 3 weeks) , concurrently with 4 cycles of albumin-bound paclitaxel and cisplatin (albumin-bound paclitaxel 125mg/m2 on days 1, 8 and cisplatin 75 mg/m2 on day 1 every 3 weeks). | Drug: anti-PD-L1 antibody<br>* Patients will receive 16 cycles of anti-PD-L1 antibody 5mg/kg IV on day 1 every 3 weeks.<br>* Other names: Socazolimab Injection;Drug: albumin bound paclitaxel<br>* Patients will receive 4 cycles of albumin bound paclitaxel 125mg/m2 on days 1, 8 every 3 weeks .<br>* Other names: ABRAXANE;Drug: cisplatin<br>* Patients will receive 4 cycles of cisplatin 75mg/m2 on day 1 every 3 weeks.<br>Procedure: radical resection of esophageal carcinoma<br>* Patients will receive radical resection of esophageal carcinoma after 4 cycles of chemotherapy.<br>|
| Placebo Comparator: placebo group<br>All patients will receive 4 cycles of placebo ( IV, every 3 weeks) , concurrently with 4 cycles of albumin-bound paclitaxel and cisplatin (albumin-bound paclitaxel 125mg/m2 on days 1, 8 and cisplatin 75 mg/m2 on day 1 every 3 weeks). | Drug: albumin bound paclitaxel<br>* Patients will receive 4 cycles of albumin bound paclitaxel 125mg/m2 on days 1, 8 every 3 weeks .<br>* Other names: ABRAXANE;Drug: cisplatin<br>* Patients will receive 4 cycles of cisplatin 75mg/m2 on day 1 every 3 weeks.<br>Drug: placebo<br>* Patients will receive 4 cycles of placebo IV on day 1 every 3 weeks.<br>Procedure: radical resection of esophageal carcinoma<br>* Patients will receive radical resection of esophageal carcinoma after 4 cycles of chemotherapy.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| major pathologic response rate | The rate of pathologic 1a and 1b after neoadjuvant chemotherapy. | Two weeks after surgery. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| R0 resection rate | The R0 resection rate of esophagectomy. | Two weeks after surgery. | 
| pathological complete response rate | The rate of pathologic 1a after neoadjuvant chemotherapy. | Two weeks after surgery. | 
| disease free survival | The 2-year disease free survival of the whole group. | From the date of surgery until the date of death due to disease progression or the date of first documented disease progression whichever came first, assessed up to 24 months. | 
| disease free survival rate | The 2-year disease free survival rate of the whole group. | From the date of surgery until the date of death due to disease progression or the date of first documented disease progression whichever came first, assessed up to 24 months. | 
| event free survival | The 2-year event free survival of the whole group. | From the date of randomization until the date of death from any cause or the date of first documented disease progression whichever came first, assessed up to 24 months. | 
| event free survival rate | The 2-year event free survival rate of the whole group. | From the date of randomization until the date of death from any cause or the date of first documented disease progression whichever came first, assessed up to 24 months. | 
| overall survival rate | The 2-year overall survival rate of the whole group. | From the date of randomization until the date of death from any cause or the date of last follow-up whichever came first, assessed up to 24 months. | 
| overall survival | The 2-year overall survival of the whole group. | From the date of randomization until the date of death from any cause or the date of last follow-up whichever came first, assessed up to 24 months. | 
| adverse events rate | The incidence rate of treatment-related adverse events of the whole group assessed by CTCAE v5.0. | From the date of randomization to 90 days after the last chemotherapy. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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esophageal cancer, immunotherapy