| Eligibility |
Inclusion Criteria:
- 1.Patients fully understand and sign ICF, voluntarily participate in the study, and
able to follow and complete all study procedures.
- 2. Aged 18-75 years (including upper and lower limits), male or female.
- 3. Patients with histologically or cytologically confirmed advanced unresectable or
metastatic solid tumors (mainly gastrointestinal tumors such as colorectal cancer and
gastric cancer, and prostate cancer)
- 4.The standard treatment failure (disease progression after treatment or treatment
side effects not tolerance), or top treatment, or shall not apply to the current
standard treatment for patients
- 5. For patients with advanced solid tumors (dose-escalation phase), at least one tumor
lesion that could be evaluated according to RECIST, version 1.1; (Dose-expansion
phase) At least one measurable tumor lesion according to RECIST, version 1.1 (a tumor
that is located in the previously irradiated area or another locoregional treatment
site and is generally not considered a measurable lesion unless there is definite
progression or persistence beyond 3 months of radiation);
- 6. ECOG physical condition=1
- 7. Patients with advanced primary liver cancer should meet the Child-Pugh liver
function grading: grade A and better grade B (=7).
- 8. With adequate bone marrow, liver and kidney organ function:
•Blood system within 14 days (not received blood transfusions or hematopoietic
stimulating factor treatment): Absolute neutrophil count (ANC) =1.5×10^9/L; Platelet
count (PLT) =75×10^9/L; Hemoglobin (Hb) =85g/L;
•Liver function: Total bilirubin (TBIL) =1.5×ULN; Alanine aminotransferase (ALT)
=3×ULN; Spread to the liver or liver cancer patient: 5 or less x ULN; Aspartate
aminotransferase (AST) or less 3 x ULN; Spread to the liver or liver cancer patient: 5
or less x ULN;
•Renal function: Creatinine (Cr) or less 1.5 x ULN; Creatinine clearance (Ccr)
(calculated only when creatinine > 1.5× ULN) =50ml/min (calculated according to
Cockcroft-Gault formula);
•Blood coagulation function: Activated partial thromboplastin time (APTT) =1.5×ULN;
International normalized ratio (INR) =1.5×ULN;
•Urinary protein: Urine routine /24 hours urine protein qualitative =1+; Or urine
protein qualitative =2+, 24 hours urine protein < 1g;
- 9. Expected survival of at least 3 months.
- 10. Women of childbearing potential had to have a negative serum or urine pregnancy
test within 7 days before the first dose. Fertile male or female patients voluntarily
during the study period and at the end of the study drug within 30 days of using
effective birth control methods, such as abstinence, the double protective screen type
cuts, condoms, contraceptive method of oral or injected contraceptives, intrauterine
device, etc. All female patients will be considered fertile unless the female patient
has undergone natural menopause, artificial menopause, or sterilization (e.g.,
hysterectomy, bilateral adnophorectomy, or radioactive ovarian irradiation).
Exclusion Criteria:
- 1. The adverse reactions of previous antineoplastic therapy have not recovered to
CTCAE 5.0 grade =1 (except for toxicities without safety risks judged by
investigators, such as alopecia, grade 2 peripheral neurotoxicity, and hypothyroidism
stable with hormone replacement therapy);
- 2. Clinically symptomatic parenchymal or leptomeningeal metastases that were judged by
the investigator to be ineligible for enrollment;
- 3. Within 4 weeks before delivery for the first time received chemotherapy, radiation
therapy, biological therapy and endocrine therapy, immune therapy, such as antitumor
drugs, with the exception of the following situations:
- Nitrosourea or mitomycin C within 6 weeks before first use of study drug;
- Oral fluorouracils and small-molecule targeted agents are administered 2 weeks
before first use of the study drug or within the five half-lives of the drug,
whichever is longer;
- Have antitumor indications for the study of the first use of drugs of traditional
Chinese medicines before 2 weeks;
- 4. Received other unlisted investigational drugs or treatments within 4 weeks before
the first dose;
- 5. Previously received EP4 inhibitor (e.g. AN0025(E7046),LY3127760,ONO-4578) for
anti-tumor treatment;
- 6. Major organ surgery (excluding needle biopsy) within 4 weeks before the first dose
of medication or requiring elective surgery during the trial;
- 7. Uncontrolled malignant pleural, ascites, or pericardial effusion that was judged by
the investigator to be ineligible for enrollment;
- 8. Unable to oral drug swallowing, or by the researchers determine the condition of
the seriously affect the gastrointestinal tract absorption, including but not limited
to, such as inflammatory bowel disease (crohn's disease and ulcerative colitis, for
example), or malabsorption syndrome, or chronic diarrhea;
- 9. Patients who received a potent inducer or inhibitor of CYP3A4 within 1 week before
the first dose or who required continued treatment with these drugs during the study;
- 10.Patients with active gastric and duodenal ulcer, ulcerative colitis and other
gastrointestinal diseases, or unresected tumor with active bleeding, or other
conditions that may cause gastrointestinal bleeding or perforation as judged by the
investigator;
- 11.Thromboembolic events (including stroke events and/or transient ischemic attack)
occurred within 12 months before the first dose of medication;
- 12.Clinically significant cardiovascular disease, including but not limited to acute
myocardial infarction, severe/unstable angina, or coronary artery bypass grafting
within 6 months before the first dose of medication; Congestive heart failure with New
York Heart Association (NYHA) grade =2; Left ventricular ejection fraction (LVEF)
<50%; A history of primary cardiomyopathy, clinically significant prolongation of the
QTc interval, or a screening QTc interval >470ms in women and >450ms in men;
- 13.Patients with active or previous autoimmune diseases with potential recurrence
(such as systemic lupus erythematosus, rheumatoid arthritis, vasculitis, etc.),
excluding patients with clinically stable autoimmune thyroid diseases and type I
diabetes mellitus;
- 14.Prior immunotherapy with grade =3 irAE or grade =2 immune-related myocarditis;
- 15.Researchers to determine the clinical significance of 3 or more electrolyte
abnormalities
- 16.Patients with active infection requiring antiinfective treatment or unexplained
fever (body temperature >38.5 ° C) during screening or before the first dose of
medication;
- 17.Patients with active pulmonary tuberculosis (TB) who were receiving anti-TB
treatment or had received anti-TB treatment within 1 year before the first dose; Known
human immunodeficiency virus (HIV) infection; Patients with a history of hepatitis B
were in the stage of active infection (HBsAg positive and HBV-DNA > the detection
limit of the research center); Patients with a history of hepatitis C were in the
active infection stage, defined as positive HCV antibody test and detectable HCV RNA;
- 18.Women who are pregnant (positive pregnancy test within 14 days before medication)
or are breastfeeding
- 19.Patients with known alcohol or drug dependence;
- 20.Patients judged by the investigator that may not be able to comply with all study
procedures;
- 21.Any other disease, metabolic abnormality, abnormal physical examinations or
laboratory abnormality with significant clinical significance. Investigator reasonably
suspects that the patient has a disease or state that is not suitable for using of the
study drug, or will affect interpretation of study results, or put the patient at high
risk.
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