| Eligibility |
Inclusion Criteria:
1. Volunteer to participate in the clinical study; be able to sign the ICF based on full
understanding and awareness of the study; have the willingness to follow and the
capacity to complete all trial procedures;
2. Aged = 18 years at the time of signing the ICF;
3. Advanced or metastatic solid malignancies confirmed cytologically or
histopathologically, prior failure of standard therapy, free of standard therapy or
intolerant of standard therapy;
4. Interval between completion of prior systemic anti-tumor treatment (chemotherapy,
targeted therapy, and immunotherapy) and the first dose in this study is = 28 days;
interval between completion of endocrine or TCM anti-tumor therapy and the first dose
in this study is = 14 days; interval between completion of any other anti-tumor
treatment with clinical study drug and the first dose in this study is = 28 days;
5. Prior anti-tumor treatment-related AE recovering to grade = 1 as per CTCAE v5.0 prior
to the first dose (except for alopecia);
6. At least one measurable target lesion assessed by the investigator according to the
RECIST v1.1 is required within 4 weeks prior to the first dose (Note: Measurable
target lesions may not be selected from the previously irradiated site. If a target
lesion at a previously irradiated site is the only optional target lesion, the imaging
data before and after significant progression of this lesion after radiotherapy
completion should be provided);
7. ECOG performance status score is 0 or 1 within 7 days prior to the first dose;
8. Life expectancy of the patient prior to the first dose judged by the investigator is =
12 weeks;
9. Major organ functions are normal;
10. Women of childbearing potential must complete a serum pregnancy test and have a
negative result within 7 days prior to the first dose;
11. Female subjects of childbearing potential or male subjects whose partners are women of
childbearing potential must agree to take at least one medically accepted
contraceptive measure (intra-uterine device, contraceptive, condom, etc.) from the
time of signing the ICF until 6 months after the last dose of the investigational
product.
Exclusion Criteria:
1. Other active malignancies within 2 years prior to the first dose of investigational
product. Localized tumors that have been cured, such as basal cell carcinoma,
squamous-cell skin cancer, superficial bladder carcinoma, prostate carcinoma in situ,
cervical carcinoma in situ, breast cancer in situ, etc., are acceptable;
2. Patients who are going to receive or have received an organ or bone marrow transplant;
3. Patients with uncontrolled pleural effusion, pericardial effusion, or ascites
requiring frequent drainage (monthly or more frequently);
4. Symptomatic brain or meningeal metastases (unless the patient has been treated for > 3
months, there is no evidence of progression on imaging within 4 weeks prior to the
first dose, and the tumor-related clinical symptoms are stable);
5. Patients with cerebrovascular accident, myocardial infarction, unstable angina, poorly
controlled arrhythmia (including QTc intervals = 450 ms in males and = 470 ms in
females) (QTc intervals are calculated by Fridericia formula) occurring within half a
year;
6. A cardiac insufficiency of Grade III or IV according to the New York Heart Association
(NYHA) classification (Appendix 6), or a left ventricular ejection fraction (LVEF) <
50% based on echocardiography;
7. Human immunodeficiency virus (HIV) infection;
8. Positive (+) for hepatitis B surface antigen (HBsAg) or positive (+) for hepatitis B
core antibody (HBcAb), with the hepatitis B virus deoxyribonucleic acid (HBV-DNA)
=2000 copies /ml, or the presence of active hepatitis determined clinically; hepatitis
C (positive for HCV antibody and positive for HCV-RNA);
9. Patients with grade 3-4 drug-related hepatitis;
10. Patients with active pulmonary tuberculosis;
11. Patients with prior and current interstitial pneumonia, pneumoconiosis, radiation
pneumonitis, drug-related pneumonia, severely impaired lung function, etc. that may
interfere with the detection and management of suspected drug-related pulmonary
toxicity;
12. Patients with known active or suspected autoimmune diseases. Patients who are allowed
to have a history of autoimmune disease at enrollment but with no requirement for
systemic immunosuppressive therapy at least 12 months prior to screening;
13. Have received treatment with live vaccines within 28 days prior to the first dose.
Patients may receive inactivated viral vaccines for seasonal influenza and 2019-nCoV
vaccines, but may not receive live attenuated influenza vaccines via intranasal route;
14. Patients requiring treatment with systemic glucocorticoids (> 10 mg/day prednisone
efficacy dose) or other immunosuppressive drugs within 14 days prior to the first dose
or during the study. However, patients are allowed to be enrolled under the following
conditions: in the absence of active autoimmune disease, patients are allowed to use
topical or inhaled glucocorticoids and adrenal glucocorticoids replacement therapy at
an effective dose equivalent to = 10 mg/day of prednisone;
15. With any serious infection requiring systemic anti-infective therapy within 14 days
prior to the first dose of the investigational product;
16. Major surgery within 28 days prior to the first dose of investigational product. A
major surgery is defined as a surgery that takes at least 3 weeks of postoperative
recovery before receiving treatment in this study;
17. Prior treatment with antibody drugs against immune checkpoint inhibitors (such as
PD-1, PD-L1, and CTLA4) or anti-4-1BB antibody drugs;
18. With a history of severe allergy to any monoclonal antibody or any excipient of the
investigational product;
19. Pregnant or lactating women;
20. Known history of psychotropic substance abuse or drug use;
21. Have other conditions not suitable for inclusion as judged by the investigator.
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