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

Air Force Military Medical University of People's Liberation Army

Status and phase: Completed; Phase 1

Conditions: Chemotherapeutic Toxicity; Immune-related Adverse Event; Gastric or Gastroesophageal Junction Adenocarcinoma

Treatments: Drug: FLOT+PD-1 antibody; Drug: SOX+PD-1 antibody

Study type: Observational

Funder types: Other

Identifiers

NCT06440811

loong-101

Details and patient eligibility

About

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.

Enrollment: 120 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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.

Trial design

120 participants in 2 patient groups

FLOT+nivolumab

Description:

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

Description:

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).