Gastric Cancer Stage IIIPhase 2NCT07257575
A Randomized Controlled Study of Serplulimab Combined With Chemotherapy for Locally Advanced Gastric Adenocarcinoma
A Phase 2 study testing FLOT (Fluorouracil+Leucovorin+Oxaliplatin+Docetaxel)+Serplulimab and FLOT (Fluorouracil+Leucovorin+Oxaliplatin+Docetaxel) in people with Gastric Cancer Stage III, run by Guangdong Provincial People's Hospital at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Gastric Cancer Stage III
- What is being tested?
- FLOT (Fluorouracil+Leucovorin+Oxaliplatin+Docetaxel)+Serplulimab and FLOT (Fluorouracil+Leucovorin+Oxaliplatin+Docetaxel)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 138 participants
- Where
- 1 siteChina
- Study dates
- 5 Jan 2025to 30 Jun 2031
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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;
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- 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).
Who cannot join
- 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.
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- 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).
- Active tuberculosis (TB), ongoing anti-TB treatment, or anti-TB treatment within 1 year prior to screening.
- History of lung diseases confirmed by imaging (preferably CT) or clinical results, such as interstitial pneumonia, non-infectious pneumonia, pulmonary fibrosis, or acute lung diseases.
- Contraindications to oxaliplatin, docetaxel, 5-FU, or leucovorin.
- Pregnant or breastfeeding women, or women who might be pregnant.
- Active hepatitis.
- Positive test results for any of the following: HIV-1 antibody, HIV-2 antibody, HTLV-1 antibody, or HCV antibody.
- Any clinically significant disease or condition deemed by the investigator to affect protocol compliance, the ability to sign the informed consent form (ICF), or suitability for participation in this clinical trial.
Trial locations and contacts
1 site in 1 country.
China1 site
No. 106, Zhongshan 2nd Road, Yuexiu District
Guangzhou, Guangdong, 510080
About this study
Official title: A Phase II Randomized Controlled Clinical Study of Serplulimab Combined With Chemotherapy in the Treatment of Patients With Locally Advanced Gastric Adenocarcinoma
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.
Read more
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
Read the detailed description
Gastric cancer (GC) remains a major global health challenge, with approximately 1 million new cases and 650,000 deaths reported annually in recent years. The incidence rate of GC is significantly higher in Asia, particularly in South Korea and China. Specifically, according to the 2020 statistics from the International Agency for Research on Cancer (IARC), China accounts for 44% of global incident cases and 48.6% of global mortality cases related to gastric cancer, respectively. Furthermore, in 2022, China recorded 358,700 new gastric cancer cases and 260,400 deaths annually. The overall survival rate and median survival time of Chinese GC patients were 33.53% and 28.68 months, respectively.
In recent years, perioperative treatment has remained a research hotspot in the field of gastric cancer. Prior to the advent of the immunotherapy era, a two-drug combination regimen (SOX regimen: oxaliplatin plus S-1) served as the primary standard of care across East Asia. Notably, findings from the RESOLVE study have established the SOX regimen as one of the standard treatment options for the perioperative management of gastric cancer in China. In contrast, based on the outcomes of the FLOT4-AIO study, the FLOT regimen has long been the cornerstone of perioperative chemotherapy for gastric cancer in Western countries. More recently, the MATTERHORN study integrated immunotherapy into the perioperative treatment landscape, with results demonstrating that the addition of immunotherapy to the FLOT regimen further significantly improves event-free survival (EFS) and overall survival (OS). The success of this pivotal study has revolutionized our understanding of perioperative immunotherapy, and the FLOT-immunotherapy combination has now gained widespread acceptance in clinical practice.
Serplulimab is a monoclonal antibody with demonstrated safety and favorable clinical efficacy across multiple cancer types. Therefore, the objective of this clinical trial is to evaluate whether FLOT chemotherapy combined with serplulimab can enhance the pathological complete response (pCR) rate in patients with stage III gastric cancer.
- Conditions
- Gastric Cancer Stage III
- Being tested
- FLOT (Fluorouracil+Leucovorin+Oxaliplatin+Docetaxel)+Serplulimab, FLOT (Fluorouracil+Leucovorin+Oxaliplatin+Docetaxel)
- Keywords
- local advanced gastric cancer, neoadjuvant chemotherapy, PD-1 inhibitor, FLOT
- Medical subject headings
- Stomach Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FLOT (Fluorouracil+Leucovorin+Oxaliplatin+Docetaxel)+SerplulimabDrug
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)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.
| Study group | Role | What they receive |
|---|---|---|
| FLOT (Fluorouracil+Leucovorin+Oxaliplatin+Docetaxel)+Serplulimab | Experimental | Not described Receives: Drug: FLOT (Fluorouracil+Leucovorin+Oxaliplatin+Docetaxel)+Serplulimab |
| FLOT (Fluorouracil+Leucovorin+Oxaliplatin+Docetaxel) | Active comparator | Not described Receives: Drug: FLOT (Fluorouracil+Leucovorin+Oxaliplatin+Docetaxel) |
What is being measured
The primary outcome is the main question the study is designed to answer.
pCR rate
pathological complete regression rate
Measured: Perioperative
Secondary outcomes (6)
MPR rate
Measured: Perioperative
R0 resection rate
Measured: Perioperative
OS
Measured: 5 years
EFS
Measured: 5 years
perioperative complication rate
Measured: Up to postoperative 30 days
Chemotherapy-related side effects
Measured: At the end of each cycle of chemotherapy (each cycle is 14 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Dec 2025
- Study start5 Jan 2025
- Primary completion31 Jan 2027 (estimated)
- Study completion30 Jun 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Gastric Cancer Stage IIIStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 138 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Guangdong Provincial People's Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Shanghai Henlius Biotech
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07257575
- Sponsor's protocol ID
- SPACE-neo
- Status last verified
- Dec 2025
- First submitted
- 10 Mar 2025
- Last updated
- 2 Dec 2025
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Randomized Controlled Clinical Study of Serplulimab Combined With Chemotherapy in the Treatment of Patients With Locally Advanced Gastric Adenocarcinoma
- ClinicalTrials.gov ID
- NCT07257575
- Acronym / sponsor ID
- SPACE-neo
- Conditions
- Gastric Cancer Stage III
- Keywords
- local advanced gastric cancer, neoadjuvant chemotherapy, PD-1 inhibitor, FLOT
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 138 participants (estimated)
- Lead sponsor
- Guangdong Provincial People's HospitalUniversity, hospital or other
- Collaborators
- Shanghai Henlius Biotech
- Study start
- 5 Jan 2025 (actual)
- Primary completion
- 31 Jan 2027 (estimated)
- Study completion
- 30 Jun 2031 (estimated)
- First posted
- 2 Dec 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Detailed description
Gastric cancer (GC) remains a major global health challenge, with approximately 1 million new cases and 650,000 deaths reported annually in recent years. The incidence rate of GC is significantly higher in Asia, particularly in South Korea and China. Specifically, according to the 2020 statistics from the International Agency for Research on Cancer (IARC), China accounts for 44% of global incident cases and 48.6% of global mortality cases related to gastric cancer, respectively. Furthermore, in 2022, China recorded 358,700 new gastric cancer cases and 260,400 deaths annually. The overall survival rate and median survival time of Chinese GC patients were 33.53% and 28.68 months, respectively.
In recent years, perioperative treatment has remained a research hotspot in the field of gastric cancer. Prior to the advent of the immunotherapy era, a two-drug combination regimen (SOX regimen: oxaliplatin plus S-1) served as the primary standard of care across East Asia. Notably, findings from the RESOLVE study have established the SOX regimen as one of the standard treatment options for the perioperative management of gastric cancer in China. In contrast, based on the outcomes of the FLOT4-AIO study, the FLOT regimen has long been the cornerstone of perioperative chemotherapy for gastric cancer in Western countries. More recently, the MATTERHORN study integrated immunotherapy into the perioperative treatment landscape, with results demonstrating that the addition of immunotherapy to the FLOT regimen further significantly improves event-free survival (EFS) and overall survival (OS). The success of this pivotal study has revolutionized our understanding of perioperative immunotherapy, and the FLOT-immunotherapy combination has now gained widespread acceptance in clinical practice.
Serplulimab is a monoclonal antibody with demonstrated safety and favorable clinical efficacy across multiple cancer types. Therefore, the objective of this clinical trial is to evaluate whether FLOT chemotherapy combined with serplulimab can enhance the pathological complete response (pCR) rate in patients with stage III gastric cancer.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 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) |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- 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;
Key exclusion criteria (22 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| FLOT (Fluorouracil+Leucovorin+Oxaliplatin+Docetaxel)+SerplulimabThe 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. | Drug | FLOT (Fluorouracil+Leucovorin+Oxaliplatin+Docetaxel)+Serplulimab |
| FLOT (Fluorouracil+Leucovorin+Oxaliplatin+Docetaxel)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. | Drug | FLOT (Fluorouracil+Leucovorin+Oxaliplatin+Docetaxel) |
Primary outcome
pCR rate
Time frame: Perioperative
pathological complete regression rate
6 secondary outcomes
MPR rate
Time frame: Perioperative
R0 resection rate
Time frame: Perioperative
OS
Time frame: 5 years
EFS
Time frame: 5 years
perioperative complication rate
Time frame: Up to postoperative 30 days
Chemotherapy-related side effects
Time frame: At the end of each cycle of chemotherapy (each cycle is 14 days)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Dec 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing FLOT (Fluorouracil+Leucovorin+Oxaliplatin+Docetaxel)+Serplulimab and FLOT (Fluorouracil+Leucovorin+Oxaliplatin+Docetaxel) in people with Gastric Cancer Stage III, run by Guangdong Provincial People's Hospital at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 2 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
pCR rate (time frame: Perioperative). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Dec 2025; AzTrials last refreshed its copy on 31 Oct 2026.