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

Lee's Pharmaceutical

Status and phase: Unknown; Phase 2; Phase 1

Conditions: Esophageal Cancer

Treatments: Drug: placebo; Drug: cisplatin; Drug: anti-PD-L1 antibody; Procedure: radical resection of esophageal carcinoma; Drug: albumin bound paclitaxel

Study type: Interventional

Funder types: Industry

Identifiers

NCT04460066

ZKAB001-LEES-2020-02

Details and patient eligibility

About

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.

Enrollment: 70 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key inclusion Criteria:

1. Aged 18 to 75 years old of either gender;

2. 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;

3. ECOG score 0-1;

4. Estimated life expectancy >3 months;

5. BMI ≥18.5kg/m2 or PG-SGA score A/B;

6. The function of important organs meets the following requirements:

   1. white blood cell count (WBC) ≥ 3.0×109/L, absolute neutrophil count (ANC) ≥ 1.5×109/L, platelets ≥ 100×109/L, hemoglobin ≥ 90g/L;
   2. ALT, AST and AKP ≤ 2.5×ULN;
   3. serum albumin ≥ 30g/L;
   4. total bilirubin ≤ 1.5×ULN;
   5. serum creatinine ≤ 1.0×ULN, creatinine clearance rate ≥60 mL/min;
   6. INR ≤ 1.5, PT≤ 1.5×ULN;

7. Cardiac function: ≤I, pulmonary function: FEV1 >1.2L, FEV1% >40%, liver function: Child-Pugh 5-6;

8. Serum HCG negative in premenopausal women ;

9. Ability to understand the study and sign informed consent.

Key exclusion Criteria:

1. Cervical esophageal carcinoma;
2. Patients who have been treated previously with anti-tumor therapy (including chemotherapy, radiotherapy, surgery, immunotherapy, etc.);
3. Known or suspected allergy or hypersensitivity to monoclonal antibodies, any ingredients of anti-PD-L1 antibody and chemotherapeutic drugs;
4. Active autoimmune diseases;
5. A history of allogeneic stem cell transplantation and organ transplantation;
6. A history of interstitial lung disease or non-infectious pneumonia;
7. Patients who cannot tolerate chemotherapy or surgery due to severe cardiac, lung, liver or kidney dysfunction, or hematopoietic disease or cachexia;
8. A history of immunodeficiency (including a positive HIV test result), or other acquired or congenital immunodeficiency diseases;
9. 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);
10. 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;
11. A history of malignancies other than esophageal cancer before enrollment, excluding non-melanoma skin cancer, in situ cervical cancer, or cured early prostate cancer;
12. Lymph node metastasis in neck, supraclavicular, abdominal cavity, retroperitoneum and pelvic cavity (except paracardial and left gastric lymph nodes).

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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70 participants in 2 patient groups, including a placebo group

PD-L1 group

Experimental group

Description:

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).

Treatment:

Drug: albumin bound paclitaxel

Procedure: radical resection of esophageal carcinoma

Drug: anti-PD-L1 antibody

Drug: cisplatin

placebo group

Placebo Comparator group

Description:

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).

Treatment:

Drug: albumin bound paclitaxel

Procedure: radical resection of esophageal carcinoma

Drug: cisplatin

Drug: placebo