| Eligibility |
Donor inclusion criteria Having provided written consent before participation in the study,
all donor candidates must fulfil all of the following criteria to be eligible for a donor
in this study.
1. Sex: Male or female
2. Age (at the time of informed consent): 19 years and older
3. Subjects with histologically- or cytologically-confirmed solid cancer In case of
hepatocellular carcinoma, clinically confirmed diagnosis as per the American
Association for the Study of Liver Diseases (AASLD) is allowed.1
4. Patients who currently maintain a CR, PR or SD per RECIST v1.12 for at least 6 months
with anti-PD-(L)1 monotherapy for solid cancer
Donor exclusion criteria The subject who meets any of the following criteria will be
excluded from a donor candidate. If an enrolled donor candidate is found to meet any of the
following criteria anytime during the study, the donated stool obtained when those
exclusion criteria are met will not be used for FMT.
1. Having taken antimicrobials (antibiotics, antivirals antifungals) in the 4 weeks prior
to donation
2. Positive result for any pathogen tests during the screening period (Table 3)
3. Current gastrointestinal symptoms including diarrhea, nausea, or vomiting
4. History of chronic gastrointestinal disease including inflammatory bowel disease,
celiac disease, or irritable bowel syndrome
5. History of systemic autoimmune disease (e.g., multiple sclerosis, connective tissue
disorder, type I diabetes mellitus)
6. History of significant neurological (except for chemotherapy-induced neuropathy),
neurodegenerative, neurodevelopmental, or psychiatric disorders
7. History or risk behaviors for infectious disease:
- History of HIV, syphilis, human T-lymphotropic virus I and II
- Current systemic infection
- Enteric pathogen infection in the last 8 weeks
- Vaccination with a live attenuated virus in the last 8 weeks
- Previous tissue/organ transplant
- Recent travel (3 months) to tropical countries, countries with endemic diarrheal
diseases or high risk of traveler's diarrhea (Africa, Southeast Asia, Mexico,
Central America, South America, Caribbean)
Recipient Main Inclusion criteria
Having provided written consent before participation in the study, patients must fulfill
all of the following criteria to be eligible for this study:
1. Sex: Male or female
2. Age (at the time of informed consent)L 19 years and older
3. Patients with histologically- or cytologically-confirmed solid cancer In case of
hepatocellular carcinoma, clinically confirmed diagnosis as per the American
Association for the Study of Liver Diseases (AASLD) is allowed.1
4. Patients who do not have standard treatment, are no longer effective, are not drug
resistant to standard treatment, or are unable to use standard treatment, and have
previously performed anti-PD-1 or anti-PD-L1-based treatment (as monotherapy or
combination therapy)
5. Patients who did not experience any of the following immune-related adverse events
(irAEs) during prior immunotherapy:
- A previous irAE corresponding to treatment discontinuation criteria for nivolumab
as described in Section 8.2.2.3
- Unresolved irAEs prior to study entry (alopecia, Grade =2 sensory neuropathy, or
other Grade =2 AEs not constituting a safety risk based on Investigator's
judgment are acceptable)
6. Patients who have at least 1 measurable lesion per the RECIST v1.12 as confirmed by
imaging within 28 days before study enrollment. The following requirements should also
be satisfied:
?If patients only have lesions that were previously treated with radiation, the lesion
should be limited to one with confirmed aggravation by imaging after radiation.
7. Eastern Cooperative Oncology Group (ECOG) performance status score of 0-2
8. Patients with a life expectancy of at least 3 months
9. Patients whose latest laboratory data meet the below criteria within 7 days before the
initiation of study treatment. If the date of the laboratory tests at the time of
study entry is not within 7 days before the initiation of study treatment, testing
must be repeated within 7 days before the initiation of study treatment, and these
latest laboratory tests must meet the following criteria. Of note, laboratory data
will not be valid if the patient has received a granulocyte colony-stimulating factor
(G-CSF) within 7 days before testing.
- White blood cells =2,000/mm3 and neutrophils =1,500/mm3
- Platelets =100,000/mm3
- Hemoglobin =9.0 g/dL
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) = 3.0 x the
upper limit of normal (ULN) of the study site (or = 5.0 x ULN of the study site
in patients with liver metastases)
- Total bilirubin = 1.5 x ULN of the study site
- Creatinine = 1.5 x ULN of the study site or creatinine clearance (either the
measured or estimated value using the Cockcroft-Gault equation) > 45 mL/min
10. Women of childbearing potential (including women with chemical menopause or no
menstruation for other medical reasons)#1 must agree to use contraception#2 from the
time of informed consent until 5 months or more after the last dose of the study
treatment. Also, women must agree not to breastfeed from the time of informed consent
until 5 months or more after the last dose of the study treatment.
11. Men must agree to use contraception#2 from the start of study treatment until 7 months
or more after the last dose of the study treatment.
- 1. Women of childbearing potential are defined as all women after the onset of
menstruation who are not postmenopausal and have not been surgically sterilized
(e.g., hysterectomy, bilateral tubal ligation, bilateral oophorectomy).
Postmenopause is defined as amenorrhea for =12 consecutive months without
specific reasons. Women using oral contraceptives, intrauterine devices, or
mechanical contraception such as contraceptive barriers are regarded as having
childbearing potential.
- 2. The subject must consent to use any two of the following methods of
contraception: vasectomy or condom for patients who are male or female subject's
partner and tubal ligation, contraceptive diaphragm, intrauterine device,
spermicide, or oral contraceptive for patients who are female or male subject's
partner.
12. Patients must be willing to provide blood and fecal samples at baseline, on-treatment,
and/or disease progression for biomarker analyses.
13. Patients who have biopsiable lesion(s) must consent to undergo fresh tumor biopsies of
accessible lesion(s).
Recipient Main Exclusion criteria Patients who meet any of the following criteria at the
time of assessment for study entry will be excluded. If an enrolled subject is found to
meet any of the following criteria before the initiation of study treatment, the subject
will not be started on study treatment and will be withdrawn from the study.
1. Patients with active malignancy within the previous 2 years before study entry (with
the exception of completely resected non-melanoma skin cancer, curatively treated
carcinoma in situ or intramucosal carcinoma, superficial bladder cancer treated with
curative intent, localized prostate cancer treated with curative intent or other
cancers that are less likely to influence on their prognosis such as localized thyroid
papillary carcinoma)
2. Patients with residual adverse effects of prior therapy or effects of surgery that
would affect the safety evaluation of the study treatment in the opinion of the
investigator or sub-investigator.
3. Patients with current or past history of severe hypersensitivity to any other antibody
products
4. Patients with active autoimmune disease with systematic treatment (i.e.,
immunomodulator, corticosteroid, or immunosuppressant) required within the past 2
years before study entry.
- Replacement therapy (e.g., thyroxine, insulin, or physiological corticosteroid
replacement therapy due to dysfunction of adrenal gland or pituitary gland, etc.)
is not regarded as a form of systematic treatment and would be allowed.
- Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with
dermatologic manifestations only (e.g., no psoriatic arthritis) may be eligible
provided that they meet the following conditions:
- Rash must cover less than 10% of the body surface area.
- Disease is well controlled at baseline and only requires low potency topical
steroids.
5. Patients with a current or past history of interstitial lung disease or pulmonary
fibrosis diagnosed based on imaging or clinical findings. Patients with radiation
pneumonitis may be enrolled if the radiation pneumonitis has been confirmed as stable
(beyond acute phase) without any concerns about recurrence.
6. Patients with concurrent diverticulitis or symptomatic gastrointestinal ulcerative or
inflammatory disease (e.g., Crohn´s disease or ulcerative colitis)
7. Patients with any metastasis in the brain or meninx that is symptomatic or requires
treatment. Patients may be enrolled if the metastasis is asymptomatic and requires no
treatment.
8. Patients with uncontrollable pericardial fluid, pleural effusion, or ascites requiring
frequent drainage (recurrence within 2 weeks of intervention)
9. Patients with uncontrollable, tumor-related pain
10. Patients who have experienced a transient ischemic attack or cerebrovascular accident
within 180 days before study entry
11. Patients with a history of uncontrollable or significant cardiovascular disease
meeting any of the following criteria:
- Myocardial infarction within 180 days before study entry
- Uncontrollable angina pectoris within 180 days before study entry
- New York Heart Association (NYHA) Class III or IV congestive heart failure
- Uncontrollable hypertension despite appropriate treatment (e.g., systolic blood
pressure =150 mmHg or diastolic blood pressure = 90 mmHg lasting 24 hours or
more)
- Clinically significant cardiac arrhythmia not controlled by adequate medication
12. Patients receiving or requiring anticoagulation therapy for a disease. Patients
receiving antiplatelet therapy including low-dose aspirin may e enrolled.
13. Patients with uncontrollable diabetes mellitus
14. Patients with systemic infections requiring treatment within 14 days before starting
the study treatment
15. Patients who have a condition requiring systemic corticosteroids (> 10 mg daily
prednisone or equivalents) (except for temporary use, e.g., for examination or
prophylaxis of allergic reactions) or other immunosuppressants within 28 days before
study entry
?Patients are permitted to use topical, ocular, intra-articular, intranasal, and
inhalational corticosteroids (with minimal systemic absorption)
16. Patients who have a history of organ transplant, including stem cell allograft
17. Patients who have received antineoplastic drugs (e.g., chemotherapy agents,
molecular-targeted therapy agents, or immunotherapy agents) within 28 days before
starting the study treatment, except for anti-PD-(L)1 inhibitor such as nivolumab,
pembrolizumab, atezolizumab, avelumab, or durvalumab, for which its regular cycle
interval is required before starting the study.
18. Patients who have undergone surgical adhesion of the pleura or pericardium within 28
days before starting the study treatment
19. Patients who have undergone major surgery under general anesthesia within 28 days
before starting the study treatment
20. Patients who have received radiotherapy within 28 days before starting the study
treatment or radiotherapy to bone metastases within 14 days before starting the study
treatment
21. Patients who have received any radiopharmaceuticals (except for examination or
diagnostic use of radiopharmaceuticals) within 42 days before the study treatment
22. Patients with known history of Human Immunodeficiency Virus (HIV) infection
23. Patients with active HBV (detectable HBs antigen or HBV DNA) or HCV infection
(detectable HCV RNA):
- For the subject receiving antiviral agents for HBV at screening, if the subject
has been treated for > 2 weeks and HBV DNA is <500 IU/mL (or 2,500 copies/mL)
prior to study entry, the subject will be allowed to be enrolled in the study.
Antiviral agent should be continued for 6 months after study treatment
discontinuation.
- For hepatocellular carcinoma, patients with past or ongoing HCV infection will be
eligible for the study.
24. Women who are pregnant or breastfeeding, or possibly pregnant
25. Patients who have received any other unapproved drug (e.g., investigational use of
drugs, unapproved combined formulations, or unapproved dosage forms) within 28 days
before starting the study treatment
26. Patients who have received a live vaccine within 4 weeks before starting the study
treatment
27. Patients judged to be incapable of providing consent for reasons such as concurrent
dementia
28. Other patients judged by the investigator or sub-investigator to be inappropriate as
subjects of this study
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