| Eligibility |
Inclusion Criteria:
1. Have signed informed consent forms voluntarily.
2. 18-80 years old.
3. Having an ECOG performance status score of 0 or 1.
4. With an expected survival of more than 12 weeks.
5. Diagnosed histologically or cytologically with local advanced or metastatic solid
cancer, and under one of following situations: standard treatment-refractory (disease
progression or no response), treatment-resistant, unable to receive treatment, or the
standard treatment is unavailable.
6. Need to provide archived tumor tissue samples (Formalin fixed or paraffin embedded
tissue blocks or at least 5 unstained sections); During the dose escalation stage, for
subjects who are unable to provide tumor samples or have insufficient samples, the
decision to enroll may be made based on specific circumstances after discussion with
the sponsor.
7. At least one assessable tumor lesion is present during the dose escalation phase, and
according to RECIST version 1.1, at least one measurable tumor lesion is present
during the dose escalation phase (CRPC can be determined based on PCWG3).
8. Having sufficient bone marrow, liver, and kidney functions (based on the normal value
of the clinical trial site):
1. Absolute neutrophil count (ANC) = 1.5×109/L.
2. Platelets = 75×109/L.
3. Hemoglobin = 90g/L.
4. Total serum bilirubin = 1.5×upper limit of normal (ULN).
5. Without liver metastases, ALT, AST = 2.5×ULN; with liver metastases, ALT, AST =
5×ULN.
6. Serum creatinine =1.5 × ULN.
7. Creatinine clearance rate (CrCl) (creatinine only ? Calculation required for 1.5
× ULN =50 mL/min (Calculate according to Cockcroft Fault formula),
8. International Normalized Ratio (INR) = 1.5×ULN, APTT = 1.5×ULN.
9. Echocardiographic LVEF (left ventricular ejection fraction) = 50%.
10. QT interval corrected by Fridericia method (QTcF) Male<450ms; Female<470ms.
9. The serum pregnancy test results of female subjects of childbearing age are negative.
10. Male or female patients of childbearing potential must agree to use effective methods
of contraception (such as double-barrier contraceptive methods, condoms, oral or
injectable contraceptives and intrauterine devices) during the study period and within
90 days after the last dosing.
Exclusion Criteria:
1. Within 3 weeks prior to the first administration, systemic anti-tumor therapy has been
received, including chemotherapy, curative radiotherapy (palliative radiotherapy for a
single lesion within 3 weeks prior to enrollment is allowed, and radiotherapy is not
allowed for measurable lesions before enrollment unless it is confirmed that the
lesion has progressed after radiotherapy), biological therapy, immunotherapy, etc.,
except for the following:
1. Received urea nitrite or mitomycin C within 6 weeks prior to the first use of the
study drug.
2. Oral administration of fluorouracil or small molecule targeted drugs within 2
weeks prior to the first use of the investigational drug or within 5 half-lives
of the drug (whichever is longer).
3. Individuals who have received endocrine therapy within 2 weeks prior to the first
use of the investigational drug.
4. Traditional Chinese patent medicines and simple preparations or traditional
Chinese medicine with anti-tumor indication within 1 week before the first use of
the study drug.
2. Patients who received other clinical trial drug within 4 weeks before the first
dosing.
3. Within 3 years prior to the first trial drug treatment, the patient had other active
malignant tumors, except for the tumors participating in this study and other locally
cured tumors (such as basal skin cancer, papillary thyroid cancer, or any type of in
situ cancer that has been completely removed, such as cervical in situ cancer, ductal
carcinoma in situ, etc.).
4. The presence of clinically uncontrollable pleural/abdominal effusion, pericardial
effusion, determined by the investigators as unsuitable for inclusion.
5. Suffering from central nervous system metastasis and/or cancerous meningitis. Except
for asymptomatic or asymptomatic central nervous system metastases that have been
clinically controlled but are judged stable by investigators, the following conditions
must also be met:
1. Stable clinical symptoms for at least 4 weeks before receiving trial drug
treatment.
2. No evidence of central nervous system disease progression was found in imaging
examinations within 4 weeks prior to the first trial drug treatment.
3. Antiepileptic drugs have been discontinued at least 2 weeks prior to the first
trial drug treatment, and the dosage of prednisone is = 10mg/day or equivalent
dose of steroids.
4. For patients with intracranial lesions, if they have received treatment (such as
radiotherapy) before the first trial drug treatment, elution should be = 2 weeks.
Cancer induced encephalitis should be excluded regardless of its stable clinical
condition.
6. Receiving drug therapy known to prolong the QT interval or potentially lead to torsade
de pointe ventricular tachycardia; Or continue to receive these medications during the
research period.
7. Acute coronary syndrome occurring within the past 6 months, including myocardial
infarction, unstable angina, symptomatic congestive heart failure (New York Heart
Association classification II-IV), aortic dissection, stroke, or other grade 3 or
higher cardiovascular and cerebrovascular events; Serious cardiac rhythm or conduction
abnormalities, such as ventricular arrhythmias requiring clinical intervention,
II-III-degree atrioventricular block, etc.
8. Suffering from clinically uncontrollable diseases, including but not limited to severe
diabetes (diabetes ketoacidosis or hyperglycemia hyperosmolality occurred within 6
months before the first administration, and the detection value of glycosylated
hemoglobin in the screening period was = 7.5%); Refractory hypertension (systolic
blood pressure = 150mmHg or diastolic blood pressure = 100mmHg after optimal medical
treatment within the first month of screening) or a history of hypertensive crisis or
hypertensive encephalopathy.
9. Individuals with previous or current interstitial lung disease (excluding radiation
pneumonia that does not require hormone therapy).
10. Evidence of persistent uncontrolled systemic bacterial, fungal, or viral infections
(including HIV infection, HIV antibody positive; syphilis infected individuals) and
current need for intravenous anti infection treatment.
11. Provisions on hepatitis B and hepatitis C: if hepatitis B surface antigen (HBsAg) is
positive, and HBV-DNA>2000 IU/ml or 104 copies/ml, hepatitis B virus infected persons
should receive antiviral treatment according to local guidelines and standards and are
willing to receive antiviral treatment throughout the study period; Hepatitis C
antibody positive, and HCV RNA higher than the upper limit of normal values in the
study site;
12. Within 14 days prior to the first administration, systemic corticosteroids
(prednisone>10mg/day or equivalent doses of similar drugs) or other immunosuppressive
treatments have been received, except for the following:
1. Use local, ocular, intra-articular, intranasal, and inhaled corticosteroids for
treatment.
2. short term use of glucocorticoids for preventive treatment (such as preventing
contrast agent allergies).
13. Within 4 weeks before the first administration or planned to receive attenuated live
vaccines during the study period.
14. Having undergone major organ surgery (excluding biopsy) or significant trauma within 4
weeks prior to the first administration or requiring elective surgery during the trial
period.
15. Individuals who have received allogeneic hematopoietic stem cell transplantation or
organ transplantation in the past.
16. Known to have alcohol or drug dependence.
17. Individuals with mental disorders or poor compliance.
18. The adverse reactions of previous anti-tumor treatments have not yet recovered to
CTCAE5.0 = Grade 1 (excluding toxicity judged by the investigators to have no safety
risk, such as hair loss, grade 2 peripheral neurotoxicity, stable hypothyroidism after
hormone replacement therapy, etc.);
19. Known to cause clinically significant allergic reactions to the active ingredients and
excipients, antibodies, and other monoclonal antibodies.
20. Pregnant (positive pregnancy test prior to dosing) or breast-feeding women.
21. The investigators believe that the subjects are not suitable to participate in this
clinical study due to other reasons.
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