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)

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

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) .

Study Overview

• Status: Recruiting
• Conditions: PD-L1 Positive Locally Advanced Patients With Resectable Gastric Cancer
• Intervention / Treatment: Drug: Drug: Toripalimab, FLOT(Docetaxel+oxaliplatin+leucovorin+5-FU)

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Ji Lin
    • Changchun, Ji Lin, China
      • Recruiting
      • First Hospital of Jilin University
      • Contact: Quan Wang, phD; Phone Number: 15843073207; Email: wquan@jlu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Informed consent of the patient;
2. 18 years old <age <75 years old;
3. The researcher judged that he could comply with the study protocol;
4. Histologically confirmed gastric or gastroesophageal junction adenocarcinoma (Siewert II-III);

5. 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
6. Immunohistochemistry confirmed that the patient was PD-L1 positive (CPS≥1);
7. 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;
8. Preoperative ASA score I-III;
9. Expected survival ≥12 weeks;

10. 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:

1. Inestigators identified stage IV (metastatic) or unresectable gastric or gastroesophageal junction adenocarcinoma
2. Previous systemic treatment for gastric cancer
3. Have a history of allergy to any component of terriprizumab, oxaliplatin, capecitabine;

4. 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;

5. History of other malignant diseases within 5 years;
6. History of active autoimmune disease or autoimmune disease
7. The subject has cardiovascular clinical symptoms or disease that is not well controlled;
8. Severe infection 4 weeks prior to first use of study drug (CTCAE > Level 2)
9. A history of interstitial lung disease (except for radiation pneumonia not treated with Chinese hormone) or non-infectious pneumonia;
10. 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;
11. Pregnant or lactating women;
12. Suffering from severe mental illness.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Toripalimab combined with FLOT regimen; 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); 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.

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Time Frame
overall survival (OS)	2 years
event-free survival (EFS)	2 years
disease-free survival (DFS)	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

Collaborators and Investigators

• Sponsor: The First Hospital of Jilin University

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2021
• Primary Completion (Anticipated): May 1, 2024
• Study Completion (Anticipated): December 1, 2024

Study Registration Dates

• First Submitted: July 18, 2022
• First Submitted That Met QC Criteria: July 18, 2022
• First Posted (Actual): July 20, 2022

Study Record Updates

• Last Update Posted (Actual): July 20, 2022
• Last Update Submitted That Met QC Criteria: July 18, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Stomach Diseases; Stomach Neoplasms; Adenocarcinoma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Protective Agents; Micronutrients; Vitamins; Antidotes; Vitamin B Complex; Docetaxel; Oxaliplatin; Leucovorin
• Other Study ID Numbers: STARS-GC04

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No