| Eligibility |
Inclusion Criteria:
1. Patients who voluntarily sign the informed consent form, understand the study and are
willing to follow and able to complete all study procedures;
2. Male or female, age = 18 years;
3. Patients who have histologically or cytologically confirmed metastatic or unresectable
locally advanced, recurrent solid tumors that are refractory to or intolerable with
standard treatment, or for which no standard effective treatment is available;
4. Patients who have an Eastern Cooperative Oncology Group (ECOG) performance status of 0
or 1;
5. Patients who have a life expectancy of at least 3 months;
6. Patients who have at least one evaluable lesion in Phase Ia study, and have measurable
lesions in Phase Ib (according to RECIST v1.1). Tumor lesions in the area of prior
radiotherapy (or other local therapy) with unequivocal progression after radiotherapy
as confirmed by imaging can be considered as measurable lesions;
7. Patients who are = 4 weeks after receiving anti-tumor therapy, such as chemotherapy,
radiotherapy, biotherapy, endocrine therapy and immunotherapy, before the first dose
of study drug, with the following exceptions: a)= 6 weeks after receiving nitrosourea
or mitomycin C before the first dose of study drug; b)= 2 weeks or 5 half-life periods
(whichever is longer) of oral fluorouracils and small molecule targeted agents before
the first dose of study drug; c)= 2 weeks after receiving traditional Chinese medicine
with anti-tumor indications before the first dose of study drug;
8. Patients who have suitable organ and hematopoietic function without severe heart,
lung, liver, renal dysfunction and immunodeficiency according to the following
laboratory tests: a)Absolute neutrophil count (ANC) = 1.5 × 109/L; b)Absolute white
blood cell count (WBC) = 3.0 × 109/L; c)Platelets = 75 x 109/L; d)Hemoglobin = 90 g/L;
e)Serum creatinine = 1.5 times the upper limit of normal (ULN); f)AST and ALT = 2.5 ×
ULN, or = 5 × ULN for patients with liver cancer or metastases to liver; g) Serum
total bilirubin (TBIL) = 1.5 × ULN; h)International normalized ratio (INR) = 1.5 × ULN
and activated partial thromboplastin time (APPT) = 1.5 × ULN (except for patients
receiving anticoagulant therapy); i)Myocardial enzyme CK and CKMB test values are
within the normal range, or mildly abnormal but judged by the investigator to be
suitable for enrollment; j)Thyroid function (FT3, FT4, and TSH) test values are within
the normal range, or mildly abnormal but judged by the investigator to be suitable for
enrollment.
9. Male subjects and female subjects of childbearing potential should agree to use
effective contraception from the signing of the informed consent form until 3 months
after the last dose.
Exclusion Criteria:
1. Subjects who have central nervous system metastasis with clinical symptoms (e.g.,
brain edema, hormone intervention required, or progression of brain metastasis) and/or
carcinomatous meningitis. However, subjects who have received prior treatment for
brain or meningeal metastases can be included if they have remained stable clinically
for at least 2 months and systemic hormone therapy (prednisone at a dose of > 10
mg/day or other hormone at an equivalent dose) has been discontinued for more than 4
weeks;
2. Subjects who fail to recover from adverse reactions of prior therapies to = CTCAE V5.0
Grade 1. (Patients with residual alopecia, chromatosis and peripheral neurotoxicity
that has recovered to = CTCAE Grade 2, and with long-term toxicity caused by
radiotherapy that cannot recover as judged by the investigator may be included);
3. Subjects with systemic diseases that have not been stably controlled after treatment,
such as history of severe cardiovascular and cerebrovascular diseases, diabetes
mellitus, hypertension, etc.;
4. Subjects who have any active auto-immune disease or evidence of auto-immune disease,
or systemic syndrome previously requiring treatment with systemic steroids or
immunosuppressive drugs. (Patients with inactive vitiligo, psoriasis and
post-treatment childhood asthma/atopy within 2 years, or thyroid disease that has been
controlled with alternative therapy/non-immunosuppression may be included);
5. For subjects requiring systemic treatment with corticosteroids (at doses equivalent to
> 10 mg prednisone/day) or other immunosuppressive agents within 14 days prior to
enrollment or during the study period, enrollment is allowed under the following
situations: a)Subjects are allowed to use topical or inhaled glucocorticoids;
b)Short-term (= 7 days) use of glucocorticoids for the prophylaxis or treatment of
non-autoimmune allergic diseases is permitted;
6. Subjects who have a history of infection with human immunodeficiency virus, or other
acquired, congenital immunodeficiency diseases, or a history of organ transplantation,
or a history of stem cell transplantation;
7. Patients with tuberculosis that is active at screening;
8. Patients with active chronic hepatitis B or active hepatitis C. Patients as hepatitis
B virus carriers, and with stable hepatitis B after drug treatment (DNA titers should
not be higher than 500 copies/mL), and cured hepatitis C (HCV RNA test results are
required to be below the lower limit of the testing site) can be enrolled;
9. Patients who have received treatment with anti-4-1BB targeting drugs;
10. Patients with a known history of severe allergic reactions (CTCAE v5.0 = Grade 3) to
macromolecular protein preparations/monoclonal antibodies, or to any component of the
study drug;
11. Patients who are expected to have major surgery during the study, including the 28-day
screening period;
12. Patients with serious infection within 4 weeks prior to the first dose, or with active
infection requiring oral or intravenous antibiotics within the first 2 weeks;
13. Patients who have participated in clinical trial of another drug within 4 weeks prior
to enrollment and enrolled for drug treatment, or are less than 4 weeks after end of
treatment (EOT);
14. Patients who have a history of alcohol abuse, drug addiction or drug abuse in the past
1 year;
15. Patients who used live attenuated vaccine within 4 weeks prior to the first dose or
plan to use such vaccine during the course of the study;
16. Patients with a previous history of definite neurological or mental disorders,
including epilepsy, dementia and poor compliance;
17. Pregnant or breastfeeding women; eligible patients (males and females) of childbearing
potential who do not agree to use a reliable method of contraception (hormonal or
barrier method, or abstinence) during the trial and for at least 3 months after the
last dose; and female patients of childbearing potential who have a positive blood or
urine pregnancy test within 7 days prior to enrollment.
18. Subjects who, in the opinion of the investigator, are not suitable for the study for
other reasons.
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