Total Neoadjuvant Immunotherapy Plus Chemotherapy for Locally Advanced Gastric or Gastroesophageal Junction Adenocarcinoma (TNICE-1)

November 6, 2026 updated by: Beijing Tsinghua Chang Gung Hospital

A Multicenter, Prospective Study of Total Neoadjuvant Immunotherapy Combined With Chemotherapy in Patients With Locally Advanced Gastric or Gastroesophageal Junction Adenocarcinoma: The TNICE-1 Study

This study is for people with locally advanced adenocarcinoma of the stomach or of the junction between the stomach and esophagus (gastroesophageal junction adenocarcinoma) that can be removed by surgery. Serplulimab (an anti-PD-1 antibody) has been approved in China for use around the time of surgery in this type of cancer. This study will evaluate a treatment approach called total neoadjuvant therapy, in which all planned immunotherapy plus chemotherapy is given before surgery.

About 42 patients will take part at 2 hospitals in China. All participants will receive serplulimab plus the SOX regimen (oxaliplatin and S-1) before surgery, followed by surgical removal of the tumor. All treatment is given before surgery. After surgery, participants will not receive additional chemotherapy or immunotherapy. They will be followed regularly with examinations and tests to check for any return of the cancer.

Researchers will collect tumor tissue, blood, and stool samples before, during, and after treatment. These samples will be used to study how the tumor and the immune system change during treatment, including the immune cells inside the tumor, the tumor's genetic features, and traces of tumor DNA in the blood. Researchers will also grow mini-tumors (organoids) from patients' tumor tissue in the laboratory to test how the tumor responds to drugs.

The study will measure how completely the tumor shrinks or disappears after treatment, the side effects participants experience, and how long participants remain free of cancer after surgery. Participants will be followed regularly after treatment ends.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

This is a multicenter, prospective clinical study of total neoadjuvant immunotherapy combined with chemotherapy in patients with locally advanced, resectable gastric or gastroesophageal junction adenocarcinoma. All participants receive a uniform regimen of the anti-PD-1 antibody serplulimab combined with the SOX regimen(oxaliplatin and S-1) administered entirely before surgery (total neoadjuvant approach), followed by radical gastrectomy. Unlike approved perioperative strategies in which immunotherapy is continued after surgery as maintenance monotherapy, this study administers the entire planned course of immunochemotherapy before surgery and does not administer any postoperative systemic therapy. The total neoadjuvant approach is intended to maximize treatment delivery while patients are treatment-naive and physiologically fit, to avoid postoperative complications delaying or preventing adjuvant therapy, and to allow pathological response at surgery to serve as an in vivo readout of treatment efficacy.

The study is embedded in a comprehensive translational research program. Longitudinal biospecimens (tumor tissue, peripheral blood, ascites if present, and stool) are collected at predefined time points. Exploratory research includes multiplex immunohistochemistry (mIHC), spatial transcriptomics, single-cell RNA sequencing, whole-exome sequencing, circulating tumor DNA (ctDNA)-based minimal residual disease (MRD) monitoring, patient-derived organoid (PDO) drug screening, gut microbiome profiling, and development of an artificial-intelligence-based model to predict treatment response. Because no postoperative therapy is administered, postoperative ctDNA-based MRD assessment is used for risk stratification and to inform individualized surveillance strategies. These analyses aim to identify biomarkers of response and resistance to total neoadjuvant immunochemotherapy and to support individualized perioperative treatment strategies.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
42

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

  • Name: Qiong Wu
  • Phone Number: +86010-56111011

Study Locations

  • China
    • Beijing Municipality
      • Beijing, Beijing Municipality, China
        • Recruiting
        • Beijing Tsinghua Changgung Hospital
        • Contact:
    • Guangdong
      • Guangzhou, Guangdong, China
        • Not yet recruiting
        • Nanfang Hospital of Southern Medical University
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Able to understand the study and provide signed informed consent (ICF)
  • Histologically confirmed adenocarcinoma of the stomach or gastroesophageal junction, clinically staged as stage II/III disease (cT1-2N+M0 or cT3-4aNxM0) based on contrast-enhanced CT/MRI
  • Willing to provide archived tumor tissue or undergo biopsy for central laboratory testing of PD-L1, EBV, and MSI/dMMR status
  • Tumor with PD-L1 CPS >=5, or MSI-H/dMMR, or EBV positivity
  • Male or female, age >=18 years
  • ECOG performance status 0-1, with no surgical contraindications
  • Life expectancy >=6 months
  • Laboratory values within 7 days prior to enrollment: absolute neutrophil count (ANC) >=1.5 x 10^9/L; platelet count >=100 x 10^9/L; hemoglobin >=90 g/L; serum albumin >=30 g/L; total bilirubin <=1.5 x ULN; AST and ALT <=2.5 x ULN (<=5 x ULN in subjects with liver metastases); creatinine <=1.5 x ULN or creatinine clearance >=50 mL/min; INR and aPTT <=1.5 x ULN (applicable only to subjects not receiving anticoagulant therapy; subjects receiving anticoagulants must be on a stable dose)
  • Good compliance and willingness to cooperate with protocol-required examinations and specimen collection (tissue, blood, stool, and saliva samples)
  • Women of childbearing potential must agree to use contraception from the time of ICF signing until at least 5 months after the last dose of study treatment or accompanying chemotherapy, and must not breastfeed; men must agree to use contraception from the first dose of study drug until at least 7 months after the last dose

Exclusion Criteria:

  • Known allergy to serplulimab or its excipients, oxaliplatin, or components of tegafur/gimeracil/oteracil potassium (S-1)
  • Prior or concurrent other malignancy (except adequately treated basal cell carcinoma of the skin or carcinoma in situ of the uterine cervix)
  • Uncontrolled pericardial effusion, pleural effusion, ascites, or gastrointestinal bleeding within 2 weeks prior to enrollment
  • Body weight loss >20% within 2 weeks prior to enrollment
  • Unable to take oral medications
  • Prior chemotherapy, radiotherapy, targeted therapy, immunotherapy, or surgery for gastric cancer
  • Prior treatment with anti-PD-1, anti-PD-L1, anti-PD-L2, or anti-CTLA-4 antibodies
  • HER2-positive tumor confirmed by central laboratory testing (IHC 3+, or IHC 2+ with positive FISH/ISH)
  • Comorbidities requiring long-term immunosuppressive therapy, or systemic or local corticosteroids at immunosuppressive doses
  • Vaccination with any anti-infectious vaccine within 4 weeks prior to enrollment
  • Uncontrolled diabetes mellitus, hypertension, or other systemic diseases
  • Currently receiving or requiring anticoagulant therapy (low-dose aspirin antiplatelet therapy allowed)
  • Any active autoimmune disease or history of autoimmune disease
  • Active tuberculosis, currently receiving anti-tuberculosis treatment, or anti-tuberculosis treatment within 1 year prior to screening
  • Confirmed interstitial pneumonitis, non-infectious pneumonitis, pulmonary fibrosis, or history of acute lung disease
  • Any contraindication to oxaliplatin or S-1
  • Pregnant or breastfeeding women
  • Active hepatitis (HBV DNA >=10^4 copies/mL or positive HCV RNA)
  • Positive HIV antibody or human T-lymphotropic virus type 1 (HTLV-1) antibody
  • Any other clinically significant disease or condition that, in the investigator's judgment, may affect protocol compliance or render the subject unsuitable for participation

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Serplulimab + SOX

All participants receive total neoadjuvant therapy consisting of serplulimab plus the SOX regimen administered entirely before surgery, followed by radical gastrectomy. No postoperative systemic therapy is administered.
Biological: Serplulimab

Anti-PD-1 monoclonal antibody administered as neoadjuvant immunotherapy in combination with the SOX regimen, given entirely before surgery (total neoadjuvant approach).

Drug: SOX regimen

Combination chemotherapy of oxaliplatin plus S-1 (tegafur/gimeracil/oteracil), administered before surgery in combination with serplulimab.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Pathological Complete Response (pCR) Rate
Time Frame: At surgery (approximately 6 months after start of study treatment)

Proportion of participants achieving pathological complete response, defined as no viable tumor cells in the resected primary tumor and lymph nodes (ypT0 ypN0), assessed by local pathology review of the surgical specimen.
At surgery (approximately 6 months after start of study treatment)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Beijing Tsinghua Chang Gung Hospital

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Tsinghua University

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Guoxin Li, Department of General Surgery, Cancer Center, Beijing Tsinghua Changgung Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
August 5, 2026

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 30, 2027

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 30, 2028

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 6, 2026

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 6, 2026

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 12, 2026

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 12, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 6, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
November 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 26768-4-01

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Individual participant data (IPD) that underlie the results reported in this study, after deidentification (text, tables, figures, and appendices), will be shared. Deidentified IPD will be made available beginning 9 months after primary completion of the study and will remain available for 5 years. Data will be shared with qualified investigators worldwide who submit a methodologically sound proposal for secondary analyses, such as individual participant data meta-analysis; proposals may be submitted at any time while the data are available. Data will be provided upon reasonable request approved by the study team, together with a signed data access agreement, through secure data transfer. The study protocol and statistical analysis plan will also be available upon request under the same terms. No re-identification of participants is permitted.

IPD Sharing Time Frame

eidentified individual participant data and supporting information (study protocol and statistical analysis plan) will be available beginning 9 months after the primary completion date of the study and will remain available for 5 years thereafter.

IPD Sharing Access Criteria

Qualified investigators affiliated with academic or research institutions may request access to the deidentified individual participant data that underlie the results reported in this study, as well as the study protocol and statistical analysis plan. Requests must include a methodologically sound research proposal and a signed data access agreement, and will be reviewed by the study team. Approved data will be provided through secure data transfer. Re-identification of study participants is not permitted. Requests may be submitted at any time while the data are available.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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