Efficacy and Safety of Neoadjuvant Nivolumab Plus SOX Versus Nivolumab Plus FLOT in Patients With HER2-negative Gastric and Gastroesophageal Junction Adenocarcinoma

Efficacy and Safety of Neoadjuvant Nivolumab Plus SOX Versus Nivolumab Plus FLOT in Patients With HER2-negative Gastric and Gastroesophageal Junction Adenocarcinoma: A Multicentre, Open-Label, Prospective Cohort Study

The goal of the study is to learn about Safety and efficacy of preoperative adjuvant SOX regimen combined with nivolumab versus FLOT Regimen with nivolumab in HER2-negative Gastric or Gastroesophageal Junction Adenocarcinoma. The main question it aims to answer are:

• Safety and efficacy of preoperative adjuvant SOX regimen combined with nivolumab versus FLOT regimen with nivolumab for the treatment of HER2-negative Gastric or Gastroesophageal Junction Adenocarcinoma.
• Disease-free survival of preoperative adjuvant SOX plus nivolumab and FLOT plus nivolumab for HER2-negative Gastric or Gastroesophageal Junction Adenocarcinoma.

Participants will be divided into two groups to use a FLOT chemotherapy regimen plus nivolumab (one group) and a SOX chemotherapy regimen plus nivolumab (another group). Researchers would compare tumor regression grade, adverse effects and survival benefit of two neoadjuvant regimens.

Study Overview

• Status: Completed
• Conditions: Chemotherapeutic Toxicity; Gastric or Gastroesophageal Junction Adenocarcinoma; Immune-related Adverse Event
• Intervention / Treatment: Drug: FLOT+PD-1 antibody; Drug: SOX+PD-1 antibody

• Study Type: Observational
• Enrollment (Actual): 120
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Shaanxi
    • Xi'an, Shaanxi, China, 710032
      • Tangdu Hospital
    • Xi'an, Shaanxi, China
      • Xijing Hospital
    • Xi'an, Shaanxi, China
      • Shaanxi Provincial People's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

The patients came from several tertiary hospitals in Xi'an city, Shaanxi Province, and were diagnosed with locally advanced gastric cancer, and the patients would accept either the neoadjuvant SOX+nivolumab or FLOT+nivolumab regimen.

Description

Inclusion Criteria:

• 1. Histopathological confirmation of GC or GEJC.
• 2. Absence of prior anti-tumor treatments, encompassing surgical resection, chemotherapy, radiotherapy, or immunotherapy.
• 3. Age within the range of 18 to 75 years.
• 4. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score of 0-1.
• 5. Absence of concurrent malignancies.
• 6. For patients with resectable GC, those with locally advanced stage III and IVA were clearly included according to the 8th edition of the American Joint Committee on Cancer (AJCC) staging system, and there were no unresectable factors.
• 7. Patients with HER-2 negative.
• 8. Basal information such as hematology and pathological histology was complete.

Exclusion Criteria:

• 1. Refusal of surgical resection subsequent to neoadjuvant therapy.
• 2. Receipt of other ICIs during the study period.
• 3. Receipt of corticosteroids during the study period.
• 4. Have received any anti-tumor therapy such as chemotherapy, radiotherapy, immunotherapy, etc., or have been more than 180 days since the last treatment.
• 5. Confirmed recurrence of GC.
• 6. Hypersensitivity to the study medication.
• 7. Systemic medical conditions contraindicating chemotherapy.
• 8. Psychiatric illnesses contraindicating chemotherapy.
• 9. Acute infections necessitating antibiotic therapy.
• 10. Uncontrolled diabetes mellitus.
• 11. Metastatic disease.
• 12. Severe malnutrition.
• 13. Active autoimmune disorders.
• 14. Pregnancy or lactation.
• 15. Positive serological test for hepatitis B or C virus infection,
• 16. Untreated central nervous system metastases peripheral neuropathy.
• 17. Severe myelosuppression.
• 18. Severe hepatic or renal insufficiency (Child-Pugh C, estimated glomerular filtration rate [eGFR] <30 mL/min).
• 19. Significant cardiac history.
• 20. Patients with a history of allogeneic organ transplantation.
• 21. History of malignancy within the past 5 years (with the exception of curative, localized cancer).
• 22. Patients with multiple factors affecting oral medication.
• 23. Vaccination within 4 weeks prior to the first dose of study drug.
• 24. Patients who have received immune checkpoint inhibitors and develop serious adverse reactions after treatment and need to be permanently disabled.
• 25. The investigator believes that the subject has other serious systemic diseases or other reasons and is not suitable for this clinical study.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
FLOT+nivolumab; Patients in the FLOT group received 4 cycles of standard FLOT chemotherapy, the FLOT chemotherapy cycle consists of: day 1: intravenous 5-FU 2600 mg/m² inserted through a peripherally inserted central catheter (PICC) for 24 hours intravenous folic acid 200 mg/m2 intravenous oxaliplatin 85 mg/m² intravenous docetaxel 50 mg/m². The next cycle of chemotherapy was repeated on day 15. Nivolumab (360 mg) was administered intravenously (IV) over 30 minutes once every 3 weeks for 6 weeks (1 cycle, 2 doses).
SOX+nivolumab; Patients in the SOX group received 3 cycles of S-1 + OXA chemotherapy prior to radical gastrectomy.The SOX chemotherapy cycle consists of: day 1: intravenous OXA 130 mg/m² days 1-14: oral S-1 80 mg/m², 2 times/Day. Repeat next chemotherapy on day 22. Nivolumab (360 mg) was administered intravenously (IV) over 30 minutes once every 3 weeks for 6 weeks (1 cycle, 2 doses).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
adverse event	adverse event caused by FLOT, SOX or nivolumab treatment, which were coded using the Medical Dictionary Regulatory Activities version 20.1 and adverse event grade according to the National Cancer Institute Common Terminology Criteria for Adverse Events	From the preoperative chemotherapy until the occurrence of adverse events, assessed up to 180 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
tumor regression grade	Residual tumor components in post-radiotherapy samples and the proportion of fibrosis	From the surgery to evaluation of tumor regression grade, assessed up to 1 week
disease-free survival	from diagnosis to recurrence or death	From date of diagnosis until the first documented recurrence or death, assessed up to 120 months
objective response rate	objective response rate defined as the proportion of patients with a complete response or partial response to treatment according to Response Evaluation Criteria in Solid Tumors (RECIST).	From the surgery to evaluation of objective response rate, assessed up to 1 week
Duration of response	Duration of response	From the first assessment of the tumor as CR or PR to the first assessment of PD (Progressive Disease) or death from any cause, assessed up to 120 months.

Collaborators and Investigators

• Sponsor: Xijing Hospital
• Investigators: Principal Investigator: Jipeng Li, Doctor, Xijing Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2021
• Primary Completion (Actual): June 1, 2022
• Study Completion (Actual): December 30, 2022

Study Registration Dates

• First Submitted: April 6, 2024
• First Submitted That Met QC Criteria: June 3, 2024
• First Posted (Actual): June 4, 2024

Study Record Updates

• Last Update Posted (Actual): June 6, 2025
• Last Update Submitted That Met QC Criteria: June 3, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: Nivolumab; FLOT; neoadjuvant chemotherapy; SOX; locally advanced; HER-negative
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Head and Neck Neoplasms; Neoplasms, Glandular and Epithelial; Esophageal Diseases; Carcinoma; Esophageal Neoplasms; Adenocarcinoma; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Antineoplastic Agents; Immunologic Factors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Nivolumab; Antibodies; Immunoglobulins
• Other Study ID Numbers: loong-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No