A Prospective, Single Center Clinical Study of Toripalimab Combined With FLOT Regimen for Perioperative Treatment of PD-L1 Positive Locally Advanced Resectable Gastric Cancer or Gastroesophageal Junction Adenocarcinoma (GEJ)

Study Overview
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Brief Summary
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In this study, patients with PD-L1 positive locally advanced patients with resectable gastric cancer or gastroesophageal junction adenocarcinoma were invited to participate in the study.To evaluate the efficacy and safety of patients with PD-L1 positive gastric cancer or gastroesophageal junction adenocarcinoma (≥T3 and the number of lymph node metastasis ≥1, and No distant metastasis) using Toripalimab combined with docetaxel, oxaliplatin, fluorouracil, leucovorin (FLOT regimen) .

Official Title
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Toripalimab Combined With FLOT Regimen for Perioperative Treatment of PD-L1 Positive Locally Advanced Resectable Gastric Cancer or Gastroesophageal Junction Adenocarcinoma (GEJ): a Prospective, Single-center Clinical Study

Conditions
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PD-L1 Positive Locally Advanced Patients With Resectable Gastric Cancer

Intervention / Treatment
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* Drug: Drug: Toripalimab, FLOT(Docetaxel+oxaliplatin+leucovorin+5-FU)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Informed consent of the patient; 18 years old <age <75 years old; The researcher judged that he could comply with the study protocol; Histologically confirmed gastric or gastroesophageal junction adenocarcinoma (Siewert II-III); Clinical stage at admission: ≥T3 with ≥1 lymph node metastasis and no distant metastasis (AJCC 8th) Esophagogastroduodenoscopy must be performed Diagnostic laparoscopy must be performed Immunohistochemistry confirmed that the patient was PD-L1 positive (CPS≥1); Preoperative ECOG [Using the ECOG scoring standard Zubrod-ECOG-WHO (ZPS, 5-point method) developed by the Eastern Cooperative Oncology Group (ECOG)] Physical State Score 0/1; Preoperative ASA score I-III; Expected survival ≥12 weeks; The baseline blood routine and biochemical parameters of selected patients should meet the following criteria: Hemoglobin ≥90g/ L, which can be met by blood transfusion; Absolute neutrophil count ≥1.5×10^9/ L Platelet count ≥100×10^9/ L Aspartic acid or alanine aminotransferase ≤ 2.5 times the upper limit Alkaline phosphatase ≤ 2.5 times normal upper limit (ULN), Thyroid stimulating hormone (TSH) ≤1 times ULN (if abnormal, T3 and T4 levels should be investigated at the same time; if T3 and T4 levels are normal, they can be included in the group); Exclusion Criteria: Inestigators identified stage IV (metastatic) or unresectable gastric or gastroesophageal junction adenocarcinoma Previous systemic treatment for gastric cancer Have a history of allergy to any component of terriprizumab, oxaliplatin, capecitabine; Received any of the following medical treatment: A. Have received anti-PD-1 or anti-PD-L1 antibody therapy in the past; B. Have received any investigational drug treatment within 4 weeks before using the drug for the first time; C. Enroll in another clinical study at the same time, unless it is an observational (non-interventional) clinical study or an interventional clinical study follow-up; D. Receive the last dose of anti-cancer treatment (including radiotherapy) within 4 weeks before the first use of the study drug;; E. Receive systematic treatment with corticosteroids (> 10mg prednisone equivalent daily dose) or other immunosuppressants within 2 weeks prior to their first use of the study drug; F. Those who have been vaccinated with anti-tumor vaccines or the study drugs have been vaccinated with live vaccines within 4 weeks before the first administration; G. Those who have undergone major surgery or trauma within 4 weeks before using the study drug for the first time; History of other malignant diseases within 5 years; History of active autoimmune disease or autoimmune disease The subject has cardiovascular clinical symptoms or disease that is not well controlled; Severe infection 4 weeks prior to first use of study drug (CTCAE > Level 2) A history of interstitial lung disease (except for radiation pneumonia not treated with Chinese hormone) or non-infectious pneumonia; Patients with active pulmonary tuberculosis infection found by history or CT examination, or patients with active pulmonary tuberculosis infection history within 1 year before enrollment, or patients with active pulmonary tuberculosis interference history more than 1 year ago but without formal treatment; Pregnant or lactating women; Suffering from severe mental illness.

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Toripalimab combined with FLOT regimen<br>The enrolled patients will receive 3 cycles of FLOT regimen +Toripalimab treatment before surgery, and every 2 weeks is a treatment cycle (Q2W). After completing the 3 cycles of treatment, the patient undergoes surgical resection.Toripalimab combined with FLOT regimen were maintained for 4 cycles after surgery. | Drug: Drug: Toripalimab, FLOT(Docetaxel+oxaliplatin+leucovorin+5-FU)<br>* FLOT: Docetaxel 50mg/m2 ivd d1 + oxaliplatin 85mg/m2 ivd d1 + leucovorin 200mg/m2 ivd d1 + 5-FU 2600mg/m2 civ, Q2W Toripalimab 3mg/kg, intravenously administered on the first day of each cycle, Q2W.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pathological complete response (pCR) |  | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| event-free survival (EFS) |  | 2 years | 
| disease-free survival (DFS) |  | 2 years | 
| overall survival (OS) |  | 2 years | 
| objective response rate (ORR) |  | 3 months | 
| R0 Surgical conversion rate |  | 3 months | 
| major pathological response (MPR) |  | 3 months | 
| Incidence and severity of adverse events |  | 6 months | 
| index of tumor-infiltrating lymphocyte (sTIL) infiltration |  | 3 months | 
| type and number of intestinal flora |  | 3 months |