| Eligibility |
Inclusion Criteria:
- 18-75 years, all genders
- Patients with histologically or cytologically confirmed advanced malignant solid
tumors who have failed standard treatment, have no standard treatment options, or are
not suitable for standard treatment at this stage.
- The interval between the first dose of investigational drug and previous major
surgery, medical device treatment, or local radiotherapy was at least 28 days. At
least 21 days between the first dose of investigational drug and previous cytotoxic
chemotherapy, immunotherapy, or biological agents; At least 14 days between he first
dose of investigational drug and previous tumor-related endocrinotherapy and minor
surgery; The interval between he first dose of investigational drug and small molecule
targeted drugs was at least 21 days or 5 half-lives, whichever is longer; At least 14
days interval between the first dose of investigational drug and antineoplastic
chinese traditional medicines.
- Patients with at least one measurable lesion on the basis of RECIST v1.1.
- ECOG = 1
- Patients are willing to provide archival tumor tissue or undergo fresh tissue biopsy.
- Life expectancy is at least 3 months.
- Having adequate organ and bone marrow functional reserve, defined as follows:
1. Blood routine (corrected with no growth factor support, blood transfusion, or
other medication within 2 weeks before screening) ANC = 1.5 ×109 /L,PLT=
75×109/L,HGB= 90 g/L
2. hepatic parameters :TBIL = 1.5 × ULN For patients with liver metastases or a
history of Gilbert's syndrome/suspected disease,TBIL = 3 ×ULN For patients
without liver metastases,ALT= 2.5 ×ULN,AST= 2.5 ×ULN For patients with liver
metastases,ALT or AST = 5 ×ULN
3. renal function:Cr= 1.5×ULN or CrCl= 45 mL/min (using The Cockcroft-Gault formula
)
4. coagulation function:APTT= 1.5 × ULN,INR= 1.5 × ULN. Patients who were in the
therapeutic window for long-term use of anticoagulants who did not meet these
criteria could be enrolled at the investigator's discretion.
- Participants are capable of providing written informed consent and adhering to the
protocol.
Exclusion Criteria:
- Past or present malignant tumor diagnosed in the past 3 years and/or required
treatment.Except for the completely resected basal and squamous cell skin cancers and
any type in situ.
- Patients with CNS metastases, unless the metastases were treated and stable for at
least 4 weeks and without taking systemic steroids = 10 mg prednisone/day or
equivalent.
- Patients suspected or confirmed immunocompromised:
1. Patients with HIV
2. Patients requiring systemic or local treatment with systemic steroids or any
immunomodulatory drug (at a level that results in a systemic dose effect).E.g.
High-dose oral or intravenous steroids > 10 mg/ day prednisone or its equivalent,
or methotrexate > 15 mg once weekly).Allow topical, inhaled or topical use of
steroids (at levels not thought to cause systemic dose effects);
3. Patients with active autoimmune disease or a history of autoimmune disease with
potential recurrence(e.g., inflammatory bowel disease, idiopathic
thrombocytopenic purpura, lupus erythematosus, autohemolytic anemia, scleroderma,
severe psoriasis, rheumatoid arthritis).Exceptions are patients with type I
diabetes, hypothyroidism that is manageable with hormone-replacement therapy,
skin conditions (e.g., vitiligo, psoriasis, or alopecia) that require no systemic
treatment, or childhood asthma/allergies that have resolved without any
intervention in adulthood.
4. Patients with allogeneic hematopoietic stem cell transplantation or organ
transplantation (except corneal transplantation)
5. Any other condition that was considered by the investigator to place the patient
at unacceptable risk as a result of receiving immunomodulatory therapy.
- Anticancer therapy, including hormonal therapy, biological therapy, cellular therapy,
or radiation therapy, was administered within 4 weeks prior to the initiation of study
treatment, except in the following cases:
1. Hormonal therapy for prostate cancer using gonadotropin-releasing hormone (GnRH)
agonists.
2. Hormone replacement therapy or oral contraceptives
- Participants with any disease, medical condition, or social factor that was judged by
the investigator to be likely to affect the study results or adherence were excluded
from the study according to the protocol:
1. Uncontrolled acute infection or confirmed bacteremia.
2. Patients with HIV or HBV,and HBV copy number > 1000/mL or HBV DNA titer > 200
IU/mL.And patients with HCV.
3. Severe dyspnea, pulmonary insufficiency, or continuous oxygen therapy.
4. The patients were classified as New York Heart Association (NYHA) class 3 or 4 or
left ventricular ejection fraction (LVEF) < 50%.
5. Myocardial infarction, unstable angina, stroke, or transient ischemic attack, or
other cardiovascular events of grade III or higher, occurred within 6 months
before dose administration.
6. Severe arrhythmia or uncontrolled hypertension (systolic blood pressure > 180
mmHg and diastolic blood pressure > 100 mmHg) or diabetes mellitus.
- Patients with uncontrolled systemic infection.
- Patients with positive treponema pallidum antibody.
- Patients who had undergone major surgical procedures (craniotomy, thoracotomy, or
laparotomy) or who had nonhealed wounds, ulcers, or fractures within 4 weeks before
the administration of the first dose of investigational drug, with the exception of
needle biopsy procedures.
- Patients with alcohol or drug dependence.
- Patients with mental disorders, including epilepsy or dementia, or poor adherence.
- Patients with tumor types of nonepithelial origin.
- Patients with received an EpCAM antibody class, CD3 dual antibody class, or CAR-T
therapy.
- Patients who did not recover to grade 1 or less toxicity (CTCAE 5.0) from previous
antineoplastic therapy(except alopecia) .Patients who did not recover to grade 1 or
below (CTCAE 5.0) after radiotherapy (except no effect).
- Pregnant (positive pregnancy test), lactating women.Women of childbearing age who did
not agree to use contraception for at least 3 months after signing the informed
consent form until the end of the study.Women of childbearing age had a positive HCG
test within 7 days before the first day of treatment.
- Male subjects who did not agree to use contraception for at least 3 months after
signing the informed consent form until the end of the study (except surgical
sterilization)
- Patients with a allergy to the study drug or its excipients.
- Patients who were deemed by the investigator to be ineligible for this study.
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