PD-1 antibody plus first-line chemotherapy for metastatic gastric cancer and gut bacteria

A Study on the Assessment of the Efficacy of PD-1 Monoclonal Antibody Combined With Chemotherapy in Metastatic Gastric Cancer Based on Gut Microbiota

This project will try combining a PD-1 antibody with standard first-line chemotherapy in people with advanced gastric cancer to see if gut bacteria predict who benefits.

Quick facts

• Study type: Observational
• Enrollment: 300 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Fudan University (Academic / other)
• Drugs / interventions: nivolumab, sintilimab, tislelizumab, pembrolizumab, fruquintinib, chemotherapy, immunotherapy
• Locations: 1 site (Shanghai, Shanghai Municipality)
• Trial ID: NCT07400354 on ClinicalTrials.gov

What this trial studies

This single-center, open-label, phase II exploratory observational study will enroll 100 patients with metastatic or locally advanced gastric cancer who have not had prior chemotherapy or immunotherapy. Participants will receive a physician-chosen standard two-drug first-line chemotherapy regimen (FOLFOX, XELOX, or SOX) together with a PD-1 monoclonal antibody (nivolumab, sintilimab, tislelizumab, or pembrolizumab), with optional fruquintinib for certain sub-enrolled patients. Stool samples for gut microbiota profiling will be collected at baseline and at predefined on-treatment time points to identify microbial patterns associated with response or resistance to the combined therapy. Clinical outcomes and laboratory data will be recorded to correlate microbiome features with treatment efficacy and safety.

Who should consider this trial

Good fit: Adults (≥18) with histologically confirmed metastatic or locally advanced gastric cancer, ECOG 0–2, adequate organ function, at least one measurable lesion, no prior chemotherapy or immunotherapy, and planned for first-line PD-1 plus chemotherapy are ideal candidates.

Not a fit: Patients who have received prior palliative chemotherapy or immunotherapy, have poor performance status or organ dysfunction that fails eligibility labs, or cannot provide required stool samples are unlikely to benefit or enroll.

Why it matters

Potential benefit: If successful, the findings could help doctors use gut microbiome tests to predict who is likely to respond to PD-1 plus chemotherapy and personalize treatment.

How similar studies have performed: Prior research in melanoma and lung cancer has shown that gut microbiota can influence response to immune checkpoint inhibitors, but using microbiome signatures to predict benefit from PD-1 combined with chemotherapy in gastric cancer remains exploratory.

Eligibility criteria

Inclusion Criteria:

* Age ≥ 18 years, gender not restricted;
* Eastern Cooperative Oncology Group (ECOG) performance status (PS) score 0-2, with -an expected survival period of more than 3 months;
* Metastatic or locally advanced gastric cancer confirmed by cytology or histopathology;
* Laboratory test data within 7 days before screening (including 7 days) should meet the following requirements: neutrophil count ≥ 1.5×109/L, platelet count ≥ 80×109/L, hemoglobin ≥ 80g/L, total serum bilirubin ≤ 1.5 times the upper limit of normal (ULN); ALT and AST ≤ 2.5 x ULN, if liver metastasis is present, ALT and AST ≤ 5 x ULN; albumin ≥ 30g/L; serum creatinine ≤ 1.5 x ULN or creatinine clearance rate (CCr) ≥ 60ml/min.
* At least one evaluable lesion (according to RECIST 1.1 criteria);
* No previous palliative chemotherapy and planned for first-line immunotherapy (nivolumab, sintilimab, tislelizumab, pembrolizumab as recommended by guidelines, specifically determined by the attending physician) combined with chemotherapy (FOLFOX, XELOX, SOX, specifically determined by the attending physician), and combination with fruquintinib is allowed (only for patients enrolled in the trial with the number HMPL-013-SH-GC103);
* The subject (or their legal representative/guardian) must sign the informed consent form, indicating that they understand the purpose of this study, are aware of the necessary procedures, and are willing to participate in this study.

Exclusion Criteria:

* Pregnant or lactating women, and women of childbearing age who have not taken adequate contraceptive measures;
* Patients with a history of other malignant tumors within 5 years, except for those with a history of cured cervical carcinoma in situ or non-melanoma skin cancer; Patients with primary brain tumors or central nervous system metastases that are not under control, and those with obvious intracranial hypertension or neuropsychiatric symptoms;
* Patients with the following severe or uncontrolled diseases: severe heart disease, unstable condition despite treatment, myocardial infarction, congestive heart failure, unstable angina pectoris, significant pericardial effusion or unstable arrhythmia within 6 months before enrollment; definite neurological or psychiatric disorders, including dementia or epileptic seizures; severe or uncontrolled infections; active disseminated intravascular coagulation, or patients with obvious bleeding tendencies;
* Patients with significant damage to important organs;
* Patients with pleural effusion or ascites causing respiratory syndrome (≥CTCAE grade 2 dyspnea) requiring local treatment;
* Other conditions where the investigator deems the patient unsuitable for participation in this trial;
* Patients who have been taking probiotics or antibiotics for a long time.

Where this trial is running

Shanghai, Shanghai Municipality

• Fudan University Shanghai Cancer Center — Shanghai, Shanghai Municipality, China (Recruiting)

Conditions Gastric Cancer; Gut Microbiota