| Eligibility |
Inclusion Criteria:
- 1 Subjects voluntarily join the study and sign an informed consent form.
- 2 Age: 18-75 years old (when signing the informed consent form); Eastern Cooperative
Oncology Group Performance status (ECOG PS) score: 0~1 points; Ected survival more
than 3 months
- 3 Advanced malignant tumors clearly diagnosed by histology or cytology.
- 4 According to RECIST 1.1 criteria, it is confirmed that there is at least one
measurable lesion;
- 5 The main organs are in good function,
- 6 Female subjects of childbearing age should agree to use contraceptive measures
during the study period and within 6 months after the end of the study;
Exclusion Criteria:
- 1 Concomitant diseases and medical history:
1. The previous pathological test was diagnosed as HER2-positive breast cancer;
2. have inflammatory breast cancer;
3. Other malignant tumors have occurred or are currently concurrently present within
3 years. The following two conditions were eligible for enrollment: other
malignancies treated with a single surgery, achieving 5 years of disease-free
survival (DFS); cured cervical carcinoma in situ, non-melanoma skin cancer, and
superficial bladder tumors [ Ta (non-invasive tumor), Tis (carcinoma in situ) and
T1 (tumor-infiltrating basement membrane)];
4. There are multiple factors that affect oral medication (such as inability to
swallow, acute and chronic diarrhea, and intestinal obstruction, etc.);
5. Unresolved toxicity of CTC AE grade 1 and above due to any previous treatment,
excluding alopecia;
6. Subjects who have undergone major surgical treatment, significant traumatic
injury, or are expected to undergo major surgery during the study period within
28 days prior to the first dose;
7. wounds or fractures that have not healed for a long time;
8. Those with a bleeding constitution; or suffering from clinically significant
bleeding (such as hemoptysis), coagulation disorders, or being treated with
antiplatelet/anticoagulants, blood transfusions or platelet transfusions;
9. Have used a strong inhibitor or inducer of CYP3A within 2 weeks before taking the
study drug for the first time;
10. Arterial/venous thrombotic events, such as cerebrovascular accident (including
temporary ischemic attack, cerebral hemorrhage, cerebral infarction), deep vein
thrombosis and pulmonary embolism, occurred within 6 months before the first
drug;
11. Those who have a history of psychotropic substance abuse and cannot quit or have
mental disorders;
12. Subjects with any severe and/or uncontrolled disease, including:
1. Poor blood pressure control (systolic blood pressure = 150 mmHg or diastolic
blood pressure = 100 mmHg);
2. Suffering from grade =2 myocardial ischemia or myocardial infarction,
arrhythmia (including: QTc =450ms for males, QTc =470ms for females) and
grade =2 congestive heart failure (New York Heart Association (NYHA)
classification);
3. Active or uncontrolled serious infection (=CTC AE grade 2 infection);
4. Liver cirrhosis; or active hepatitis: hepatitis B reference: HBsAg positive,
and HBV DNA detection value exceeds the upper limit of normal; hepatitis C
reference: HCV antibody positive, and HCV virus titer detection value
exceeds the upper limit of normal; Note: Those who meet the entry
conditions, subjects who are positive for hepatitis B surface antigen or
core antibody, and subjects with hepatitis C, need to continue antiviral
treatment to prevent virus activation;
5. Active syphilis infection;
6. Renal failure requiring hemodialysis or peritoneal dialysis;
7. History of pulmonary interstitial fibrosis, drug-induced interstitial lung
disease; or evidence of active pneumonia found on chest CT scan during
screening;
8. Those with a history of immunodeficiency, including HIV positive or other
acquired or congenital immunodeficiency diseases, or a history of organ
transplantation;
9. Those who suffer from epilepsy and need treatment;
- 2 Tumor-related symptoms and treatment:
1. Received surgery, chemotherapy, radiotherapy or other anti-cancer therapy within
4 weeks before the first dose (calculated from the end of the last treatment);
those who have received local radiotherapy in the past can be included in the
group if they meet the following conditions: The study treatment started more
than 4 weeks (more than 2 weeks for brain radiotherapy); and the target lesions
selected in this study were not in the radiotherapy area; or the target lesions
were located in the radiotherapy area, but progress was confirmed;
2. Received NMPA-approved Chinese patent medicines with anti-tumor indications in
the drug instructions within 2 weeks before the first administration (including
Compound Cantharidin Capsule, Kangai Injection, Kanglaite Capsule/Injection, Aidi
Injection, Brucei Oil Injection /capsule, Xiaoaiping tablet/injection,
cinobufacin capsule, etc.) treatment;
3. Imaging (CT or MRI) shows that the tumor has invaded around important blood
vessels or the investigator judges that the tumor is very likely to invade
important blood vessels and cause fatal bleeding during the follow-up study;
4. Uncontrolled pleural effusion, pericardial effusion or ascites that still
requires repeated drainage (judgment by the investigator);
5. Brain metastases, spinal cord compression, cancerous meningitis with clinical
symptoms (unless asymptomatic, or treated and stable, no imaging evidence of new
brain metastases or brain metastases expansion has been found for at least 2
weeks after treatment for brain metastases , and discontinued steroid or
anticonvulsant therapy for at least 14 days prior to initiation of study
treatment).
- 3 Study treatment related:
1. Vaccination history of live attenuated vaccine within 28 days before the first
dose or plan to receive live attenuated vaccine during the study period;
2. Allergic constitution, or known allergy to the active ingredients or excipients
of the study drug;
3. Active autoimmune disease requiring systemic therapy (eg, use of
disease-modifying drugs, corticosteroids, or immunosuppressants) within 2 years
prior to initiation of study treatment; alternative therapy (eg, thyroxine,
insulin, or adrenal or pituitary therapy) Physiological corticosteroids for
insufficiency, etc.) are not considered systemic therapy;
4. Diagnosed with immunodeficiency disease or are receiving systemic glucocorticoid
therapy or any other systemic immunosuppressive therapy (dose >10mg/day
prednisone or other equivalent therapeutic hormone), and still within 2 weeks
before the start of study treatment in continued use;
5. are using drugs known to prolong the QTc interval;
6. is taking a drug known to cause sinus bradycardia.
- 4 Those who participated in clinical trials of other anti-tumor drugs within 4 weeks
before enrollment or did not exceed 5 drug half-lives;
- 5 Any factors that increase the risk of QTc interval prolongation or risk of
arrhythmia, such as heart failure, hypokalemia, congenital long QT syndrome, family
history of long QT syndrome, or unexplained occurrence in first-degree relatives
younger than 40 years of age sudden death;
- 6 Any factors that may increase the risk of sinus bradycardia, such as hyperkalemia,
hypothyroidism, etc.;
- 7 According to the judgment of the investigator, there are concomitant diseases that
seriously endanger the safety of the subjects or affect the completion of the study,
or subjects who are considered unsuitable for enrollment for other reasons.
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