Study of FMT Combined With Nivolumab in Gastric Cancer

Study Overview
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Brief Summary
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This study is a single-arm, single center study. The purpose of this study is to evaluate the efficacy and safety of FMT capsules XBI-302 combined with Nivolumab in the treatment of anti-PD-1/L1 resistant gastric cancer.

Detailed Description
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The primary purpose of this single-arm, open-label, single center trial is to evaluate the efficacy and safety of XBI-302 combined with Nivolumab in the treatment of anti-PD-1/L1 resistant gastric cancer. During treatment period, all eligible subjects will receive XBI-302 with Nivolumab following gut preparation. The imaging evaluation of efficacy will be performed every 6 weeks.

Official Title
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Evaluating the Efficacy and Safety of FMT Capsules XBI-302 Combined With Nivolumab in the Treatment of Anti-PD-1/L1 Resistant Gastric Cancer

Conditions
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Gastric Adenocarcinoma, Esophagogastric Junction Adenocarcinoma, Esophagus Adenocarcinoma

Intervention / Treatment
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* Drug: XBI-302 + Nivolumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Voluntarily participate in this study and provide written informed consent Age ≥ 18 years and ≤70 years, male or female Pathological confirmed locally advanced, unresectable or metastatic gastric adenocarcinoma, esophagogastric junction adenocarcinoma and lower esophagus adenocarcinoma that are resistant to anti-PD-1/L1 antibodies Able and willing to provide tumor tissue At least one measurable extracranial target lesion according to iRECIST Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 Life expectancy ≥3 months Exclusion Criteria: History of other primary malignancies within 5 years except adequately treated in situ carcinoma of the cervix or non-melanoma carcinoma of the skin Had systemic diseases that were difficult to control within 4 weeks prior to screening History of anti-PD-1 antibodies related adverse reactions that led to the permanent withdrawal of anti-PD-1 therapy History of coagulation disorders Mechanical or paralytic obstruction of the gastrointestinal tract Anticipated to receive a great number of antibiotics during study period

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: XBI-302 + Nivolumab<br>FMT capsules XBI-302 will be administered orally every two weeks for 12 weeks and then every four weeks for 12 weeks. Nivolumab will be intravenously infused every two weeks for 24 weeks. | Drug: XBI-302 + Nivolumab<br>* After gut preparation, a single dose of FMT will be performed via oral administration. Subsequently, nine combined treatment cycles that composed of anti-PD-1 infusions (Nivolumab at 240 mg, q2w) and additional FMT capsules, and 3 single treatment cycles of anti-PD-1 infusions will be administered.<br>* Other names: FMT + PD-1 inhibitor;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease control rate | iCR + iPR + iSD rate according to iRECIST criteria | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease control rate | iCR + iPR + iSD rate according to iRECIST criteria | 6, 12, 18 weeks | 
| Objective response rate | iCR + iPR rate according to iRECIST criteria | 24 weeks | 
| Changes of intestinal microbiota characteristics between responders and non-responders | To compare the change of intestinal microbiota characteristics between responders and non-responders | 24 weeks | 
| Changes of related immune cells in peripheral blood between responders and non-responders | To compare the change of related immune cells in peripheral blood between responders and non-responders | 12 weeks | 
| Change of CD8+T cell counts in tumor tissue between responders and non-responders | To compare the change of CD8+T cell counts in tumor tissue between responders and non-responders | 6 weeks | 
| Change of CD8+T cell counts in intestinal tissue between responders and non-responders | To compare the change of CD8+T cell counts in intestinal tissue between responders and non-responders | 6 weeks | 
| Incidence and severity of AEs that related to XBI-302 | Rate of adverse events and their severity that are determined to be related to XBI-302 | 24 weeks | 
| Incidence and severity of immune related AEs | Rate and severity of irAEs | 24 weeks |