| Eligibility |
Inclusion Criteria:
- Subjects are eligible to be included in the study only if all of following criteria
apply:
1. Voluntarily agree to sign informed consent, understand the study and is willing
and able to comply with all the trial procedures.
2. Male or female subject aged 18-70 years (including the boundary value).
3. Eastern Cooperative Oncology Group performance status of 0 to 1.
4. Patients with cytologically or histopathological confirmed advanced malignant
solid tumors that is refractory/relapsed to standard therapy (with disease
progression or intolerance) or lack of effective treatment, or the subject
refuses standard therapy.
5. At least one extracranial lesion according to the Response Evaluation Criteria in
Solid Tumors (RECIST v1.1) for response assessment, including measurable and
non-measurable lesions. The number of subjects with all non-measurable lesions
should be no more than 1/3 of the total enrolled subjects.
6. Life expectancy = 12 weeks, per investigator's discretion.
7. For subjects who have received prior anti-tumor therapy, as follows:
- Systemic radiotherapy = 3 weeks before the first dose, local radiotherapy to
bone metastasis = 2 weeks prior to the first administration of study
treatment.
- Previous chemotherapy, immunotherapy (PD-1 antibody, PD-L1 antibody or
CTLA-4 antibody, etc.), biological anti-tumor therapy (tumor vaccine,
cytokines or growth factors), and targeted therapy = 4 weeks before the
first dose (small molecule targeted therapy = 2 weeks prior to the first
dose).
- Received previous immunotherapy, such as PD-1 antibody, PD-L1 antibody or
CTLA-4 antibody, etc. Subjects never experienced a toxicity leading to
permanent discontinuation of prior immunotherapy.
- Previously received anti-tumor herbal medicine or medications which content
herbal ingredient approved for anticancer, with an interval of = 2 weeks
prior to the first dose.
8. Patients with asymptomatic central nervous system (CNS) metastasis or
asymptomatic brain metastasis after treatment, free of disease progression by
computed tomography (CT) or magnetic resonance imaging (MRI) scan and be stable
for at least 4 weeks without steroid therapy.
9. Adequate organ and bone marrow hematopoietic function, as evidenced by:
- Absolute neutrophil count (ANC) = 1.5 × 109/L.
- Absolute white blood cell count (WBC) = 3.0 × 109/L.
- Platelet count = 100 × 109/L.
- Hemoglobin = 100 g/L (no blood transfusion within 2 weeks prior to signing
informed consent).
- Serum creatinine = 1.5 x upper limit of normal (ULN).
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =2.5 ×
ULN (ALT and AST =5 × ULN for subjects with liver metastases).
- Serum total bilirubin (TBIL) = 1.5 x ULN.
- International normalized ratio (INR) = 2 x ULN or activated partial
thromboplastin time (APTT) = 1.5 x ULN (except for patients receiving
anticoagulant therapy).
10. Men with reproductive capacity or women with the possibility of pregnancy must
use highly effective contraceptive methods (such as oral contraceptives,
intrauterine contraceptive devices, abstinence or barrier contraception combined
with spermicide) during the trial, and continue contraception for 12 months after
the end of treatment.
11. Voluntarily agrees to participate by signing written informed consent and is
willing and able to comply with protocol and scheduled visits.
Exclusion Criteria:
- Subjects are excluded from the study if any of the following criteria apply:
1. Patients with other malignant tumors within 5 years before enrollment, except
cured cervical carcinoma in situ and cured cutaneous basal cell carcinoma.
2. Failure to recover from previously treated adverse reactions to CTCAE 5.0 grade =
1, except for residual alopecia effects.
3. Active, or history of, autoimmune diseases that may recur (eg, systemic lupus
erythematosus, rheumatoid arthritis, inflammatory bowel disease, autoimmune
thyroid disease, multiple sclerosis, vasculitis, glomerulonephritis, etc.), or
are at high risk (eg, receiving an immunosuppressive treatment for an organ
transplant). however, subjects with the following are allowed to enroll:
- Type I diabetes that is stable after a fixed dose of insulin.
- Only requiring hormone replacement therapy for autoimmune hypothyroidism.
- Skin diseases not requiring systemic treatment (such as eczema, rash
accounting for less than 10% of body surface, psoriasis without ophthalmic
symptoms, etc.).
4. Planning major surgery during the study, the 28-day screening period included.
5. Requiring systemic corticosteroids (dose equivalent to >10 mg prednisone/day) or
other immunosuppressive drugs within 14 days before the first dose of study
treatment or during the study. The following are allowed:
- Use of topical or inhaled glucocorticoids
- A brief course of corticosteroids (=7 days) for prophylaxis or for treatment
of non-autoimmune conditions.
6. Currently suffering from acute lung disorders, interstitial lung disease,
interstitial pneumonia, pulmonary fibrosis, radiation pneumonitis, etc.
7. Uncontrolled systematic diseases and stable after treatment, such as
cardiovascular disorders (unstable angina pectoris or myocardial infarction 6
months prior to the first dose, etc.) diabetes, hypertension, etc.
8. Arterial or venous thrombotic or embolic events, such as cerebrovascular accident
(including transient ischemic attack), deep vein thrombosis or pulmonary embolism
within 6 months prior to first dose.
9. History of infection with human immunodeficiency virus, or other acquired,
congenital immunodeficiency diseases, or history of organ transplantation, or
history of stem cell transplantation.
10. Patients with a history of pulmonary tuberculosis or pulmonary tuberculosis at
screening.
11. Patients with active chronic hepatitis B or active hepatitis C. Hepatitis B virus
carriers, patients with stable hepatitis B after drug treatment (DNA titer should
not be higher than 500 IU/mL or copy number < 1000 copies/ml) and cured hepatitis
C patients (HCV RNA test negative) can be enrolled.
12. Severe infections within 4 weeks before the first dose of study treatment, or
active infections within 2 weeks before the first dose that require oral or
intravenous antibiotics.
13. Subjects with known previously serious allergic reactions to macromolecular
protein preparations/monoclonal antibodies, or to any component of the
investigational product (CTCAE 5.0 = grade).
14. Participation in other drug clinical trials within 4 weeks prior to the first
dose.
15. Alcohol dependence or history of drug abuse or drug abuse within the past 1 year.
16. Patients with a clear history of neurological or psychiatric disorders, such as
epilepsy, dementia, and poor compliance.
17. Female subject who is pregnant or lactating.
18. Patients with uncontrolled pleural effusion, abdominal effusion, or pericardial
effusion.
19. Received hematopoietic stimulating factors, such as colony stimulating factor and
erythropoietin within 2 weeks before the first dose of study treatment.
20. Subjects who, per the opinion of the investigator, are not suitable for
participation in this trial for other reasons.
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