This study is designed to improve the response rate of anti-PD-1 among patients with
anti-PD-1 resistant/refractory digestive (including gullet, stomach and intestine) system
cancers through the intervention on their gut microbiota. Healthy people who have the gut
microbiota profile similar to the responders of anti-PD-1 therapy will be identified. The gut
microbiota of these healthy people will be extracted to product FMT capsule. Gastrointestinal
(GI) cancer patients who failed anti-PD-1 treatment will be administrated with anti-PD-1
immunotherapy combined with FMT. The enrolled subjects will firstly receive 1-week of FMT
therapy. Subsequently, each anti-PD-1 treatment will be combined with the maintenance dose of
FMT capsules to ensure the efficiency of gut microbiota colonization. Each subject will
receive anti-PD-1 therapy for 6 cycles. After the completion of both 3 and 6 cycles of
therapy, safety and efficacy assessments will be conducted. The subjects who complete 3
cycles of treatment but are clinically evaluated as disease progression will not continue to
the following 3 cycles of treatment.
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.
