| Eligibility |
Inclusion Criteria:
1. Volunteer to participate and sign the informed consent form.
2. Age = 18 years old, regardless of gender.
3. Patients with unresectable or metastatic advanced solid tumors confirmed by histology
or cytology.
4. Subjects with advanced malignant solid tumors who had disease progression or
intolerance and no satisfactory alternative treatment with at least first-line
standard treatment.
Note: If recurrence occurs during adjuvant/neoadjuvant therapy or within 6 months
after completion, adjuvant/neoadjuvant therapy is considered to be the first-line
treatment for advanced disease.
5. Have not received immune checkpoint inhibitor treatment.
6. Patients with the following tumor types: small cell lung cancer, cervical cancer,
endometrial cancer, ovarian cancer, vulvar cancer, neuroendocrine tumors, salivary
gland cancer, thyroid papillary or follicular cancer, skin squamous cell carcinoma,
skin malignant melanoma , Merkel cell tumor, head and neck squamous cell carcinoma,
colorectal cancer, gastric cancer, bladder cancer, cholangiocarcinoma, etc.
7. Have tissue and blood samples that can detect TMB specimen.
8. There is at least one measurable lesion (RECIST 1.1 standard).
9. ECOG score of 0 or 1.
10. The expected survival period is = 12 weeks.
11. Sufficient organ and bone marrow function (no hematopoietic growth factor, blood
transfusion or platelet therapy was given within 7 days before the first study drug
treatment):
1. Blood routine: absolute neutrophil count (ANC) =1.5×109/L, platelet =100×109/L
and hemoglobin =90 g/L;
2. Liver function: serum total bilirubin = 1.5 times the upper limit of the normal
reference range (×ULN); when there is no liver metastasis, alanine
aminotransferase (ALT) and aspartate aminotransferase (AST) = 2.5 × ULN; ALT and
AST =5 × ULN in liver metastasis;
3. Renal function: subjects with serum creatinine = 1.5 × ULN or creatinine level>
1.5 times ULN, measured or calculated according to Cockcroft-Gault formula
creatinine clearance rate = 60.0 mL / min;
4. Coagulation function: International normalized ratio (INR) = 1.5 and partially
activated prothrombin time (aPTT) = 1.5 × ULN; (For patients undergoing
anticoagulation therapy, the investigator judges that both INR and aPTT are safe
and effective treatments Within);
5. Heart function: left ventricular ejection fraction (LVEF) detected by
echocardiography>50%
12. Women with fertility must have a negative serum pregnancy test within 7 days before
the first medication. Reproductive male or female patients voluntarily use effective
contraceptive methods, such as double-barrier contraceptive methods, condoms, oral or
injectable contraceptives, intrauterine devices, etc., from signing the informed
consent until 90 days after the last study medication. All female patients will be
considered fertile unless the female patient has been naturally menopausal, has
undergone artificial menopause, or has been sterilized (such as hysterectomy,
bilateral adnexectomy).
Exclusion Criteria:
1. Participate in the clinical trials of other investigational drugs or investigational
devices within 28 days before the first medication; or have received anti-tumor
treatment within 2 weeks, including but not limited to chemotherapy and radiotherapy
(allowed to complete the palliative at least 1 week before the study drug treatment
Radiotherapy) or targeted therapy.
2. The toxicity of previous anti-tumor treatments has not recovered to 0 or 1 level (hair
loss, peripheral neurotoxicity caused by chemotherapy = 2 can be selected). Subjects
who need to use corticosteroids (> 10 mg/day prednisone equivalent dose) or other
immunosuppressive drugs for systemic therapy within 14 days before the study drug is
administered.
Note: If there is no active autoimmune disease, inhaled or topical steroid hormones,
or adrenal hormone replacement therapy with a prednisone equivalent dose of = 10 mg
per day is allowed. Allow short-term (= 7 days) use of glucocorticoids for preventive
treatment (for example, for subjects with a history of severe allergies, when other
anti-allergic drugs cannot be used instead to prevent allergy to contrast agents,
researchers can use glucocorticoids according to local diagnosis and treatment
routines Prevention) or for the treatment of non-autoimmune diseases (for example,
delayed type hypersensitivity caused by contact allergens).
3. Subjects who have active, or have had autoimmune diseases or risks that may recur (for
example, an organ transplant that requires immunosuppressive therapy). However,
subjects with type I diabetes, hypothyroidism requiring only hormone replacement
therapy, or skin diseases that do not require systemic treatment (for example,
vitiligo, psoriasis, or hair loss) are allowed to be included in the group. For any
uncertain situation, it is recommended to consult the sponsor's medical monitor before
signing the informed consent.
4. Major surgery (except for biopsy) or the surgical incision did not heal completely
within 4 weeks before the first study drug treatment.
5. Suffered from other known malignant tumors within 2 years before enrollment (except
for treated skin basal cell carcinoma, skin squamous cell carcinoma and/or carcinoma
in situ after radical resection).
6. Untreated brain metastases and Symptomatic brain metastasis or spinal cord compression
after treatment ; for patients with brain metastases who have previously received
treatment, if the clinical and imaging evidence does not indicate disease progression
within 4 weeks before the first study drug treatment, and 2 weeks before the first
administration There is no need to receive corticosteroid treatment and can be
considered for inclusion.
7. Previous history of interstitial lung disease, drug-induced interstitial lung disease,
radiation pneumonia, symptomatic interstitial lung disease or any evidence of active
pneumonia detected by chest CT scan within 4 weeks prior to first study drug therapy.
8. Subjects with a history of active tuberculosis infection within 1 year before the
first study administration and a history of active tuberculosis infection more than 1
year ago were considered suitable for inclusion if the investigator determined that
there was no evidence of active tuberculosis at present.
9. Mental or substance abuse disorders that are known to interfere with test compliance.
10. A history of human immunodeficiency virus (HIV) infection or an active bacterial or
fungal infection requiring systematic treatment in the 14 days prior to initial study
drug therapy.
11. Uncontrolled hepatitis virus infection (positive for HBV DNA or HCV RNA) .
12. Within 4 weeks of initial administration, there is ascites requiring drainage or
diuretic treatment, or pleural or pericardial effusion requiring drainage and/or
symptoms of tachypnea.
13. Cardiovascular disease with significant clinical significance.
14. Receive live or attenuated live vaccine within 4 weeks prior to the first study drug
treatment.
15. History of severe allergic reaction to humanized antibodies or fusion proteins.
16. Any other disease , and the investigator had reason to suspect that the patient was
not eligible for study drug therapy.
17. Part II: The results of tumor tissue samples were MSI-H
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