A Randomized Controlled Study of Serplulimab Combined With Chemotherapy for Locally Advanced Gastric Adenocarcinoma

NCT07257575 | Active Not Recruiting Phase 2

• 1 other identifier: SPACE-neo
• Study Type: interventional
• Target: 138
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to learn if FLOT chemotherapy combined with serplulimab can improve the pathological complete response (pCR) rate in patients with stage III gastric cancer. The main question it aims to answer is: Can FLOT chemotherapy combined with serplulimab improve the pathological complete response (pCR) rate in patients with stage III gastric cancer? Researchers will compare serplulimab with a blank control group to see if it can improve the pathological complete response (pCR) rate in patients with stage III gastric cancer. Participants will : Receive serplulimab combined with FLOT chemotherapy or FLOT chemotherapy alone every 2 weeks Undergo imaging assessments at 4 weeks and 8 weeks Undergo surgery based on imaging results after 8 weeks Receive postoperative serplulimab combined with adjuvant chemotherapy or adjuvant chemotherapy alone

Conditions

Gastric Cancer Stage III

Keywords

local advanced gastric cancer; neoadjuvant chemotherapy; PD-1 inhibitor; FLOT

Outcome Measures

Primary Outcomes (1)

• pCR rate

  pathological complete regression rate

  Perioperative

Secondary Outcomes (6)

• MPR rate

  Perioperative

• R0 resection rate

  Perioperative

• OS

  5 years

• EFS

  5 years

• perioperative complication rate

  Up to postoperative 30 days

Study Arms (2)

FLOT (Fluorouracil+Leucovorin+Oxaliplatin+Docetaxel)+Serplulimab

EXPERIMENTAL

Drug: FLOT (Fluorouracil+Leucovorin+Oxaliplatin+Docetaxel)+Serplulimab

FLOT (Fluorouracil+Leucovorin+Oxaliplatin+Docetaxel)

ACTIVE COMPARATOR

Drug: FLOT (Fluorouracil+Leucovorin+Oxaliplatin+Docetaxel)

Interventions

FLOT (Fluorouracil+Leucovorin+Oxaliplatin+Docetaxel)+Serplulimab DRUG

The subjects will first receive four cycles of neoadjuvant FLOT (Fluorouracil+Leucovorin+Oxaliplatin+Docetaxel) combined with serplulimab treatment, administered once every two weeks (Q2W). Imaging assessments will be conducted after the completion of the 2nd and 4th cycles of neoadjuvant therapy, followed by standard surgery. Postoperatively, they will continue with four cycles of adjuvant chemotherapy based on fluoropyrimidine combined with serplulimab, starting 4-6 weeks after surgery.

FLOT (Fluorouracil+Leucovorin+Oxaliplatin+Docetaxel)+Serplulimab

FLOT (Fluorouracil+Leucovorin+Oxaliplatin+Docetaxel) DRUG

The subjects will first receive four cycles of neoadjuvant FLOT (Fluorouracil+Leucovorin+Oxaliplatin+Docetaxel) treatment, administered once every two weeks (Q2W). Imaging assessments will be conducted after the completion of the 2nd and 4th cycles of neoadjuvant therapy, followed by standard surgery. Postoperatively, they will continue with four cycles of adjuvant chemotherapy based on fluoropyrimidine, starting 4-6 weeks after surgery.

FLOT (Fluorouracil+Leucovorin+Oxaliplatin+Docetaxel)

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Have a full understanding of the study and voluntarily sign the Informed Consent Form (ICF);
• The tumor is located in the stomach, pathologically confirmed as adenocarcinoma, with clinical stage III (cT3-4aN1-3M0) determined by enhanced CT/MRI examination;
• Tumor specimens show PD-L1 positivity (CPS ≥ 1). At the time of enrollment, there must be sufficient tumor tissue available for assessing PD-L1 expression levels (subjects undergoing repeated screening do not need additional PD-L1 testing);
• No restriction on gender, aged 18-70 years;
• Generally in good condition, with an ECOG performance status of 0-1, and no contraindications to surgery;
• Physical condition and organ function allow for major abdominal surgery;
• Expected survival ≥ 3 months;
• Laboratory test results within 7 days prior to enrollment must meet the following criteria:
• WBC \> 3.50 × 10⁹/L and \< 9.50 × 10⁹/L, ANC \> 1.5 × 10⁹/L, Hb ≥ 80 g/L, PLT ≥ 100 × 10⁹/L;
• Serum bilirubin ≤ 1.5 × ULN, AST and ALT ≤ 2.5 × ULN;
• Creatinine ≤ 1.5 × ULN or serum clearance \> 60 ml/min;
• INR and aPTT ≤ 1.5 × ULN (for subjects not receiving anticoagulation therapy); subjects receiving anticoagulants must be on a stable dose;
• Demonstrates good compliance and is able to cooperate with the study protocol's laboratory, auxiliary examinations, and relevant specimen collection;
• Women of childbearing potential (including those in menopause due to chemotherapy or other medical reasons) must agree to use contraception from the time of signing the ICF to at least 5 months after the last dose of study treatment or concurrent chemotherapy (whichever is later). They must also agree not to breastfeed during this period. Men must agree to use contraception from the initiation of the study drug to at least 7 months after the last dose of study drug or concurrent chemotherapy (whichever is later).

You may not qualify if:

• HER2-positive status, defined as IHC3+ or IHC2+ with FISH+; or known MSI-H/dMMR.
• Tumor involvement of the esophagogastric junction (EGJ).
• Known allergy to citric acid monohydrate, sodium citrate dihydrate, mannitol, or polysorbate (components of the investigational drug).
• History or concurrent diagnosis of other malignancies (excluding completely resected basal cell carcinoma, stage I squamous cell carcinoma, carcinoma in situ, mucosal carcinoma, superficial bladder cancer, or any other cancer with no recurrence for at least 5 years).
• Uncontrolled pericardial effusion, pleural effusion, ascites, gastrointestinal bleeding, or high bleeding risk within 2 weeks prior to enrollment.
• Weight loss exceeding 20% within 2 weeks prior to enrollment.
• Inability to take oral medication.
• History of chemotherapy, radiotherapy, immunotherapy, or surgery for gastric cancer.
• Previous treatment with anti-PD-1, anti-PD-L1, anti-PD-L2, or anti-CTLA-4 antibodies (or any other antibody targeting T-cell co-stimulatory or checkpoint pathways).
• Tyrosine kinase inhibitor treatment within 2 weeks prior to enrollment.
• Long-term use of immunosuppressive drugs or systemic/local corticosteroids at immunosuppressive doses (e.g., \>10 mg/day prednisone or equivalent).
• Vaccination with any anti-infective vaccine (e.g., influenza, varicella) within 4 weeks prior to enrollment.
• Uncontrolled systemic diseases, such as diabetes or hypertension.
• Current or required anticoagulant therapy (except for low-dose aspirin used as antiplatelet therapy).
• Active autoimmune diseases or history of autoimmune diseases (e.g., interstitial pneumonitis, uveitis, colitis, hepatitis, hypophysitis, nephritis, hyperthyroidism, hypothyroidism; exceptions include vitiligo or childhood asthma resolved without intervention; patients requiring bronchodilators for asthma are excluded).

Sponsors & Collaborators

• Guangdong Provincial People's Hospital: lead
• Shanghai Henlius Biotech: collaborator

Study Sites (1)

No. 106, Zhongshan 2nd Road, Yuexiu District

Guangzhou, Guangdong, 510080, China

Location

MeSH Terms

Conditions

Stomach Neoplasms

Condition Hierarchy (Ancestors)

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 10, 2025
• First Posted: December 2, 2025
• Study Start: January 5, 2025
• Primary Completion (Estimated): January 31, 2027
• Study Completion (Estimated): June 30, 2031
• Last Updated: December 2, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)