Efficacy and Safety of Serplulimab Combined With Chemotherapy as Neoadjuvant Treatment for Locally Advanced Gastric Cancer or Adenocarcinoma of Esophagogastric Junction

NCT06576921 | Recruiting Phase 2 DMC

• 1 other identifier: XJH-AEG/GC-001
• Study Type: interventional
• Target: 116
• Locations: 1 country
• Sites: 5

Brief Summary

This is a multicenter, double-blind, randomized, phase 2 trial to investigate the efficacy and safety of serlulimab combined with nab-paclitaxel plus SOX versus nab-paclitaxel plus SOX alone as neoadjuvant treatment for locally advanced GC or AEG. The goal of this clinical trial is to learn if serlulimab combined with nab-paclitaxel plus SOX as neoadjuvant treatment for locally advanced AEG/GC. It will also learn about the safety of serlulimab combined with nab-paclitaxel plus SOX. The main questions it aims to answer are: Does serlulimab increase the pCR of participants with locally advanced AEG/GC ? What medical problems do participants have when taking serlulimab? Researchers will compare to a placebo (a look-alike substance that contains no drug) to see if serlulimab combined with nab-paclitaxel plus SOX as neoadjuvant treatment for locally advanced AEG/GC. Participants will: Eligible patients were randomly assigned to receive serlulimab (4.5 mg intravenously on day 1) combined with chemotherapy (nap-paclitaxel 260 mg/m2 intravenously on days 1, OXA 130mg/ /m2, intravenously on days 1, and S-1 40 to 60 mg orally twice daily depending on BSA on days 1 to 14) or chemotherapy alone every 3 weeks for 3 preoperative cycles followed by 3 postoperative cycles. All patients will be followed for survival.

Conditions

Stomach Neoplasms; Immune Checkpoint Inhibitors

Keywords

Gastric cancer; Adenocarcinoma of Esophagogastric junction cancer; PD-1 antibody

Outcome Measures

Primary Outcomes (1)

• Pathological complete response rate (pCR)

  postoperative pathological response according to the Mandard tumor regression grading system (TRG), TRG 1 is pCR.

  3 weeks after completion of the neoadjuvant treatment phase

Secondary Outcomes (8)

• R0 resection rate

  30 days after completion of the surgery phase

• 1 year Progression-free survival rate (PFS)

  1 year

• Adverse event (AE)

  90 days after completion of treatment

• Morbidity

  30 days after completion of the surgery phase

• Mortality

  30 days after completion of the surgery phase

Study Arms (2)

S-P-SOX group

EXPERIMENTAL

Neoadjuvant treatment phase: 1.Serplulimab, 4.5 mg intravenously on day 1; 2.Nap-paclitaxel, 260 mg/m2 intravenously on days 1; 3.Oxaliplatin (OXA), 130mg/ /m2, intravenously on days 1; 4.Tigio (S-1), 40-60 mg orally twice daily on days 1 to 14. The above treatments will be administered every 3 weeks for three preoperative cycles. Dose adjustment is not allowed and delayed dosing is allowed. Surgery phase: Surgery was scheduled 3 to 4 weeks after completion of the last cycle of neoadjuvant treatment. All surgical procedures are performed according to the guidelines of the Japanese Research Society for the Study of Gastric Cancer. Adjuvant treatment phase: Adjuvant treatment started 3 to 8 weeks after surgery. Patients will receive three 3-week cycles of adjuvant treatment with S-P-SOX.

Drug: Serplulimab Combined With Chemotherapy

P-SOX group

PLACEBO COMPARATOR

Neoadjuvant treatment phase: 1.Nap-paclitaxel, 260 mg/m2 intravenously on days 1; 2.Oxaliplatin (OXA), 130mg/ /m2, intravenously on days 1; 3.Tigio (S-1), 40-60 mg orally twice daily on days 1 to 14. The above treatments will be administered every 3 weeks for three preoperative cycles. Dose adjustment is not allowed and delayed dosing is allowed. Surgery phase: Surgery was scheduled 3 to 4 weeks after completion of the last cycle of neoadjuvant treatment. All surgical procedures are performed according to the guidelines of the Japanese Research Society for the Study of Gastric Cancer. Adjuvant treatment phase: Adjuvant treatment started 3 to 8 weeks after surgery. Patients will receive three 3-week cycles of adjuvant treatment with P-SOX.

Drug: Placebo combined with Chemotherapy

Interventions

Serplulimab Combined With Chemotherapy DRUG

Serplulimab (Dosage form: Lyophilized powder; Unit dose strength: 4.5 mg; Route of administration: IV infusion; Storage requirements: 2-8℃. Protect from light and freezing.) Nap-paclitaxel (Dosage form: Lyophilized powder; Unit dose strength: 100 mg; Route of administration: IV infusion; Storage requirements: \<25℃. Protect from light.) S-1 (Dosage form: Capsule; Unit dose strength: 20 mg; Route of administration: Oral; Storage requirements: 20-30℃. Protect from light.) Oxaliplatin (Dosage form: Lyophilized powder; Unit dose strength: 50 mg; Route of administration: IV infusion; Storage requirements: \<25℃. Protect from light.) Surgery: All surgical procedures are performed according to the guidelines of the Japanese Research Society for the Study of Gastric Cancer.

Also known as: Nap-paclitaxel, S-1, Oxaliplatin, surgery

S-P-SOX group

Placebo combined with Chemotherapy DRUG

Placebo (Dosage form: Lyophilized powder; Unit dose strength: 4.5 mg; Route of administration: IV infusion; Storage requirements: 2-8℃. Protect from light and freezing.) Nap-paclitaxel (Dosage form: Lyophilized powder; Unit dose strength: 100 mg; Route of administration: IV infusion; Storage requirements: \<25℃. Protect from light.) S-1 (Dosage form: Capsule; Unit dose strength: 20 mg; Route of administration: Oral; Storage requirements: 20-30℃. Protect from light.) Oxaliplatin (Dosage form: Lyophilized powder; Unit dose strength: 50 mg; Route of administration: IV infusion; Storage requirements: \<25℃. Protect from light.) Surgery: All surgical procedures are performed according to the guidelines of the Japanese Research Society for the Study of Gastric Cancer.

Also known as: Nap-paclitaxel, S-1, Oxaliplatin, surgery

P-SOX group

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age older than 18 and younger than 75 years
• Primary GC or AEG (Siewert II/III)confirmed pathologically by endoscopic biopsy
• Clinical stage T3/T4N+M0 disease as assessed by CT/MRI, PET-CT, and laparoscopy, if feasible
• At least one measurable lesion according to the RECIST, version 1.1
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Surgical treatment after neoadjuvant chemotherapy is planned according to clinical staging criteria.
• Life expectancy of at least 3 months
• Acceptable bone marrow, hepatic, and renal function, including: a)Blood routine examination(No blood transfusion within 14 days; No granulocyte colony-stimulating factor (G-CSF) or other hematopoietic stimulating factors were used): white blood cell count ≥3.5 ×109/L, neutrophils ≥1.5 × 109/L, platelet count \>100 × 109/L, and hemoglobin ≥90 g/L; b)Hepatic function: alanine aminotransferase (ALT) and aspartate aminotransferase (AST), ALT and AST≤2.5×ULN; total bilirubin (TBIL) ≤1.5×ULN (Gilbert syndrome patients, ≤3×ULN); c)Renal function: serum creatinine (Cr) ≤1.5×ULN or creatinine clearance (Ccr) ≥60mL/ min; d)Coagulation function: activated partial thromboplastin time (APTT), international standardized ratio (INR), prothrombin time (PT) ≤1.5×ULN;
• Written informed consent

You may not qualify if:

• Squamous cell carcinoma, adenosquamous cell carcinoma, small cell carcinoma, and undifferentiated gastric cancer were confirmed by pathology
• Positive Her-2 detection (IHC3+ or IHC2+ amplified by FISH detection)
• Prior chemotherapy, radiotherapy, hormone therapy, targeted therapy, or immunotherapy
• Contraindications for surgical treatment or chemotherapy
• Presence of distant metastasis
• History of other malignant disease within the past 5 years, except: basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that have been treated radically and have shown no signs of disease for at least 5 years
• Any active or history of autoimmune disease, or history of syndrome that required systemic steroids or immunosuppressive medications, except for subjects with vitiligo or resolved childhood asthma/atopy
• History of immunodeficiency diseases, including human immunodeficiency virus (HIV), or other acquired or congenital immune-deficient disease, or transplantation
• Severe mental disorder
• Presence of digestive tract obstruction, jaundice, acute infectious diseases, inflammatory bowel disease, Crohn's disease, ulcerative colitis, chronic diarrhea, active tuberculosis
• Immunosuppressive drugs are required for 2 weeks or within 2 weeks or during the study period, excluding the following: a) intranasal, inhaled, topical or topical steroid injections (e.g. intra-articular injections); b) Physiological dose of systemic corticosteroids (≤10mg/ day prednisone or equivalent dose); c) Short-term (≤7 days) use of steroids for the prevention or treatment of non-autoimmune allergic diseases;
• Patients who have undergone major surgery or received live virus vaccine within 4 weeks
• Pregnant or breast-feeding women, subjects who are unwilling to receive effective contraception during treatment and within 6 months after the end of treatment (including male subjects who have the ability to impregnate women and female subjects and their male partners)
• Evidence of bleeding tendency or receiving thrombolytics or anticoagulants
• According to the criteria of the term Common Adverse Events (NCI-CTCAE V5.0), the corresponding symptoms have been diagnosed;

Sponsors & Collaborators

• Xijing Hospital: lead
• Tang-Du Hospital: collaborator
• Hebei Medical University Fourth Hospital: collaborator
• Tianjin Medical University Cancer Institute and Hospital: collaborator

Study Sites (5)

The fourth hospital of Hebei Medical University

Shijiazhuang, Heibei Province, 050000, China

RECRUITING

Department of Digestive surgery, Xijing Hospital of Digestive Diseases, Air Force Medical University, Xi' an, China

Xi'an, Shaanxi, 710032, China

RECRUITING

Department of General Surgery, Tangdu Hospital, Air Force Medical University

Xi'an, Shaanxi, 710032, China

RECRUITING

Department of General Surgery, The 986th Military Hospital, Air Force Medical University

Xi'an, Shaanxi, 710032, China

RECRUITING

Tianjin Medical University Cancer Institute & Hospital

Tianjin, 300060, China

RECRUITING

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MeSH Terms

Conditions

Stomach Neoplasms

Interventions

Drug Therapy; S 1 (combination); Oxaliplatin; Surgical Procedures, Operative

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases

Intervention Hierarchy (Ancestors)

Therapeutics; Coordination Complexes; Organic Chemicals

Study Officials

• Liu Hong, Ph.D

  Xijing Hospital of Digestive Diseases, Xijing Hospital, Air force Medical University, Changlexi ST 15, Shaanxi Province, 710032, China

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Zhenshun Li, Ph.D

CONTACT

15922893108; 769054503@qq.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: During the study, the subjects, the investigator, the sponsor, and the designees are not aware of the randomized allocation, except in the event of emergency unblinding. During the course of treatment with the study drug, if the investigator determines that the study drug is related to a life-threatening situation of the subject, and the investigator considers that knowing the medication of the subject is conducive to the handling of adverse events, an emergency unblinding is allowed. Two sets of sealed blind envelopes were prepared. In the event of an emergency unblinding, the identification number will be used to open the retained envelope to complete the unblinding process.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This study employed block randomization to allocate subjects in a 1:1 ratio to either the experimental or control group. To ensure balance in sample size between the groups, the randomization sequence was generated using SAS 9.4 software. The randomization list was generated by an independent statistician and securely stored in a password-protected computer system, with corresponding envelopes prepared.

Study Record Dates

• First Submitted: August 26, 2024
• First Posted: August 29, 2024
• Study Start: November 15, 2024
• Primary Completion (Estimated): May 31, 2026
• Study Completion (Estimated): September 30, 2026
• Last Updated: April 23, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (5)