| Eligibility |
Subjects must meet all of the following criteria to be included in this study:
1. They voluntarily participate in the clinical study; fully understand, are informed
about this study and sign the Informed Consent Form; are willing to follow and have
the ability to complete all trial procedures.
2. Subjects are required to meet the following criteria: they must be subjects with
histologically or cytologically confirmed advanced malignant solid tumors who do not
respond to, or are intolerant to, or reject standard treatment, or receive no
effective treatment;
3. =18 years old, both male and female;
4. They have an expected survival of = 3 months;
5. Their performance status score is 0 to 1 according to the Eastern Cooperative Oncology
Group (ECOG) criteria;
6. There is at least one measurable or assessable lesion according to RECIST V1.1;
7. The organ function must meet the following requirements:
7.1 No serious hematopoietic abnormalities (no blood transfusion, and no use of blood
products, granulocyte colony-stimulating factors, platelet-stimulating factors or
other hematopoietic growth factors for correction within 14 days prior to the
screening lab test): hemoglobin (HGB) = 90 g/L, neutrophil count (ANC) = 1.5 × 109 /L,
platelet count (PLT) = 100 × 109 /L; 7.2 Liver function: alanine aminotransferase
(ALT), aspartate aminotransferase (AST) = 2.5 times the upper limit of normal (ULN)
(subjects without liver metastases) or = 5 × ULN (subjects with liver metastases);
serum total bilirubin = 1.5 × ULN, total bilirubin levels in subjects with Gilbert's
syndrome = 3.0 × ULN; 7.3 Coagulation function: prothrombin time (PT), international
normalized ratio (INR) and partial thromboplastin time (APTT) = 1.5 × ULN; 7.4 Renal
function: Creatinine (Cr) = 1.5 × ULN and serum creatinine clearance rate = 50 ml/min
(see Appendix 1);
8. Eligible subjects (male or female) of childbearing potential must agree to take a
medically approved contraceptive measure (e.g., intrauterine device, pill, or condom)
during the trial and for 3 months after the last dose; female subjects of childbearing
potential must have a negative pregnancy test result during the screening period and
must be non-lactating; See Appendix 2 for specific contraception measures.
Criteria for exclusion
Meeting any 1 of the following exclusion criteria results in exclusion:
1. Subjects are known (including suspected) allergic to the active ingredient MNC-168 or
its excipients, or have an allergic constitution (excluding mild asymptomatic seasonal
allergies);
2. Subjects have difficulty swallowing or do not tolerate venipuncture or have a history
of needle and blood sickness;
3. Toxic reactions from prior antineoplastic therapy have not returned to grade 1 or
below (Grade > 1 based on CTCAE 5.0, except for toxicity such as alopecia, which in
the judgment of the investigator is not a safety risk);
4. Subjects have bleeding tendencies or are on thrombolytic or anticoagulant therapy.
5. Subjects have received immunosuppressive drugs within 14 days before signing informed
consent, except in the following cases:
5.1 Intranasal, inhalation, topical steroid or topical steroid injection (such as
intra-articular injection); 5.2 Systemic corticosteroid therapy with prednisone or its
equivalent physiological dose not more than 10 mg/day; 5.3 Use of steroids as
prophylactic drugs for allergic reactions (such as pretreatment before computed
tomography [CT]).
6. Subjects have received an allogeneic tissue/solid organ transplant;
7. Subjects develop spinal cord compression, brain metastases or meningeal metastases,
excluding those who do not need steroid therapy after surgery, whole brain
radiotherapy or stereotactic radiosurgery, and whose disease is stable for = 8 weeks
and/or = 4 weeks before the first administration;
8. Subjects have had a cerebrovascular accident or a history of transient ischemic attack
within 6 months prior to signing the informed consent form;
9. Subjects require systemic antibacterial, antiviral or antifungal therapy for any
uncontrolled active infection at the time of signing the informed consent and/or
within 1 week prior to Cycle 1 Day 1 (C1D1); and subjects have received a course of
systemic antibiotics within 2 weeks prior to C1D1;
10. Subjects have a history of other primary malignancies within 5 years prior to the
investigational therapy, with the following exceptions: radically treated malignancies
that have not recurred, such as cervical carcinoma in situ, basal cell carcinoma of
the skin or squamous cell carcinoma;
11. Subjects have active gastrointestinal diseases or other diseases that may
significantly affect the absorption, distribution, metabolism or excretion of MNC-168;
12. Subjects have a clear history of neurological or psychiatric disorders (including
epilepsy and dementia);
13. Subjects have received chemotherapy, radiotherapy or biological anticancer therapy,
herbal therapy with antitumor effects, and palliative local radiotherapy within 2
weeks prior to the first dose;
14. Subjects have taken live biotherapeutic products (LBPs), prebiotic foods and/or
beverages and/or supplements (e.g., yogurt) within 1 week prior to the first dose or
require regular doses of LBPs, prebiotic foods or supplements during the study period;
15. Subjects have received fecal transplantation, preparation of spores or other fecal
materials, isolated bacterial products, genetically engineered bacteria, or similar
drug treatment;
16. Subjects have participated in a clinical trial of another investigational drug or
investigational device within 4 weeks (or 5 half-lives of the drug, whichever is more
appropriate in the judgment of the investigator) prior to the first dose; note:
subjects who have entered the follow-up phase of a clinical study may be eligible as
long as it has been more than 4 weeks (or 5 half-lives of the drug, whichever is more
appropriate in the judgment of the investigator) since the last dose in the previous
study;
17. Subjects have undergone major surgical procedures or active ulcers or wounds that have
not fully healed within 4 weeks prior to the first dose of the trial; or require major
surgical procedures during the trial;
18. Subjects develop peripheral neuropathy = grade 2;
19. Subjects have clinically significant cardiovascular diseases, including any of the
following cases:
19.1 Subjects have a history of myocardial infarction (within 6 months prior to
trial), severe or unstable angina, coronary or peripheral artery bypass grafting; 19.2
New York Heart Association (NYHA) grade 3~4 heart failure; 19.3 Cardiac function: left
ventricular ejection fraction (LVEF) < 50%. 19.4 Poorly controlled hypertension
(systolic blood pressure = 150 mm Hg and/or diastolic blood pressure = 95 mm Hg); 19.5
Subjects are considered by the investigator to have clinically significant arrhythmias
or electrocardiographic (ECG) abnormalities, such as the mean of three heart
rate-corrected QT intervals (QTcF) intervals of > 470 msec calculated for three
12-lead ECG measurements performed at the investigation site; 19.6 Subjects are
currently receiving certain medications that have a known risk of prolonging the QT
interval or inducing tip-twist ventricular tachycardia and are unable to discontinue
the medication or switch to another medication 1 week prior to the start of treatment
with the investigational drug.
20. Subjects were HIV-infected or active hepatitis B virus-infected (HBsAg and/or HBcAb
positive with a peripheral blood hepatitis B virus DNA titer test = 1 × 103 IU/ml), or
active hepatitis C virus-infected (hepatitis C virus antibody positive with hepatitis
C virus RNA = 500 IU/ml);
21. Subjects have received an attenuated/inactivated vaccine within 28 days prior to
signing informed consent or are scheduled to receive an attenuated/inactivated vaccine
during the screening period;
22. Subjects, in the judgment of the investigator, have a serious concomitant disease that
endangers the safety of the subject, or interferes with the subject's ability to
complete the study;
23. Subjects are those with a history of psychotropic substance abuse or drug use;
24. Or an investigator has determined that the subject has other conditions that make
him/her eligible for the study.
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