Fecal Microbiota Transplant (FMT) Capsule for Improving the Efficacy of Anti- PD-1

Inclusion Criteria:

1. Patients have a histologically or cytologically confirmed diagnosis of unresectable or metastatic solid tumors originating from the GI tract.
2. Patients are able and willing to provide pathological tissue embedded in the wax blocks or paraffin sections.
3. Patients who have received any number of radiation therapy, chemotherapy, vaccine therapy or other oncological therapy are permitted.
4. Patients are currently receiving or have received at least 2-dose injection of systemic PD-1 immunotherapy. The results of hospital imaging examination were confirmed as progressive disease (PD). According to iRECIST, PD is defined as an increase in the length of the lesion > 20% or occurrence of new lesion or non-target lesion progression. Anti-PD-1 drugs contain pembrolizumab, nivolumab or any other anti-PD-1 drugs that haspassed phase 2 clinical development. Patients are eligible when the previous failed anti-PD-1 treatment was initiated within one year of the first dose of this trial.
5. Patients are willing and able to swallow at least 20 FMT capsules.
6. Patients must be willing and able to sign the informed consent form.
7. Patients consent to receive follow-up medical imaging to determine disease progression, and provide stool samples before and after taking capsules at each follow-up visit.
8. Patients must be at least 18 years old, regardless male or female..
9. Patients need to have basic physical movement with ECOG scale of 0 or 1.
10. For women with childbearing potential, the results of blood pregnancy test within 7 days prior to enrollment or the results of urine pregnancy test within 72 hours prior to enrollment must be negative.
11. Patients must have basic body function. Blood test results need to reach the following indexes: Absolute neutrophil count (ANC)≥1500/mcL, platelets≥100,000/mcL, hemoglobin≥9 g/dL or 5.6 mmol/L, no transfusion or EPO dependency (within 7 days of assessment), serum creatinine≤1.5×upper limit of normal (ULN) or creatinine clearance≥60 mL/min, serum total bilirubin≤1.5×ULN or direct bilirubin≤ULN, AST (SGOT) and ALT (SGPT)≤2.5×ULN for patients with serum total bilirubin >1.5 ULN or ≤5×ULN for patients with liver metastases, albumin≥2.5 mg/dL, coagulation indexes INR or PT ≤1.5×ULN. Unless patient is receiving anticoagulant therapy, coagulation indexes should be within normal range of therapy.
12. Expected survival duration≥3 months.

Exclusion Criteria:

1. Patients with irritable bowel syndrome, toxic megacolon, severe dietary allergies (including severe allergic to shellfish, nuts, seafood).
2. Patients who have responded to anti-PD-1 therapy or are in stable disease status (per iRECIST).
3. Patients are participating in any other clinical trial within 4 weeks before the first dose of FMT capsule treatment.
4. Patients with highly severe symptom (including rapidly declining on ECOG performance; rapidly worsening symptoms; lesion transferring to critical sites and requiring urgent medical intervention).
5. Patients have a known history of malignant blood diseases, has a primary brain tumor or sarcoma, or other primary solid tumors except digestive system tumors.
6. Has progressing CNS metastases or leptomeningeal metastasis. Patients with stable brain metastases must be re-screened by brain MRI brain or CT scan within two weeks before enrollment to ensure no disease progression, and simultaneously take ≤10mg steroid daily one week before study beginning. Patients with no history of CNS metastases or no signs of CNS metastases do not need another medical imaging examination for brain diseases.
7. Had a severe hypersensitivity reaction to anti-PD-1 immunotherapy.
8. Has an autoimmune disease or a history of autoimmune disease or requires treatment of systemic steroid (prednisone >10 mg daily or equivalent dose of similar drugs) or immunosuppressive agents. The following cases are excepted: local, ophthalmic, intra-articular, intranasal, or inhaled corticosteroids with extremely low systemic absorption, hormone replacement therapy, short-term (≤7 days) treatment of corticosteroids for preventive use (e.g., allergy to contrast agents).
9. Currently has pneumonitis or a history of (non-infectious) pneumonitis that required steroid therapy.
10. Has severe cardiovascular disease (e.g., drug-uncontrolled congestive heart failure, hypertension, cardiac ischemia, myocardial infarction, and severe cardiac arrhythmia), bleeding disorders, severe obstructive or restrictive pulmonary diseases, systemic infections.
11. Has active human immunodeficiency virus (HIV) infection (performance as HIV 1/2 antibodies and/or positive).
12. Has active Hepatitis B (HBV) or Hepatitis C (HCV) infection.
13. Has known active tuberculosis.
14. Has received a live vaccine or live attenuated vaccine within 4 weeks prior to enrollment.
15. Has appeared adverse events (per CTCAE 5.0, ≥grade 2) due to drug treatment within 4 weeks and not recovered from it. Patients who have undergone major surgery must have completely recovered from toxicity and complications of previous interventions before study beginning.
16. Has received anti-tumor therapy except experimental drugs (e.g., chemotherapy, targeted small molecule therapy or radiotherapy) within 2 weeks before screening or plans to receive anti-tumor therapy except experimental drugs (e.g., chemotherapy, targeted small molecule therapy or radiotherapy) during the study period. Radiotherapy used for pain controlling is excepted.
17. Has known history of psychiatric or drug abuse.
18. Patient is pregnant or breastfeeding, or subjects (including male subject and his female spouse) cannot take effective contraceptive measures from signing the informed consent to 120 days after the final anti-PD-1 therapy combined with FMT treatment.
19. Patients who cannot stop antibiotics treatment 24 hours before administration due to infection, etc.
20. Other cases that investigators think patients cannot participate in the study, e.g., any medical history, treatment history, or history of abnormal test data that possibly confuses the study results, or interferes with patients' participation in the whole study, or damages patient interests.