| Eligibility |
Inclusion Criteria:
1. Age: = 18 years old and = 80 years old, gender: male or female;
2. The investigator evaluated the expected survival period to be at least 3 months;
3. The requirement of the ECOG physical fitness score is 0 or 1;
4. Patients with advanced malignant tumors who have failed to receive standard treatment,
have no standard treatment, do not tolerate standard treatment or refuse to accept
standard treatment confirmed by cytology or pathology;
5. There must be an evaluable tumor focus in the dose increasing stage, and at least one
measurable tumor focus in the dose expanding stage (solid tumors refer to RECIST 1.1
standard, lymphoma refer to Lugano 2014 evaluation standard);
6. It has sufficient organ and bone marrow reserve function, which is defined as follows:
System laboratory reference value:
Blood routine (no blood transfusion, no use of hematopoietic stimulating factor and no
use of drugs to correct blood cell count within 14 days before the first
administration):
Absolute neutrophil count = 1.5 x 109/L;Platelet count = 90 x109/L;Hemoglobin = 90g/L;
Coagulation function:
International standardized ratio (INR) and activated partial thromboplastin time
(APTT) = 1.5xULN (without anticoagulant treatment), those who receive oral
anticoagulant treatment and whose INR is 2~3 can be included.
Liver function:
Total bilirubin (TBIL) = 1.5xULN;Hepatocellular carcinoma, Gilbert's syndrome, liver
metastasis = 2xULN;Alanine aminotransferase (ALT), aspartate aminotransferase (AST) =
2.5xULN;Hepatocellular carcinoma, liver metastasis = 5xULN renal function Serum
creatinine or Serum creatinine clearance = 1.5xULN or>50ml/min (using Cockcroft-Gault
formula, see appendix)
7. Agree to provide archived pathological tissue or fresh biopsy tumor tissue for the
detection of PD-L1, CD47 expression level or receptor occupancy and other
pharmacodynamic indicators (not as a necessary inclusion standard); Female patients
with fertility must have negative serum pregnancy test within 7 days before the first
administration and are willing to take effective birth control/contraception methods
to prevent pregnancy during the study period until 6 months after the last
administration of the study. Male patients must agree to take effective contraceptive
methods during the study period and within 6 months after the last administration of
the study; Postmenopausal women must have amenorrhea for at least 12 months before
they are considered infertile.
Exclusion Criteria:
1. Have received any anti-CD47 antibody and SIRP within 4 weeks before the first
administration a Antibodies or CD47/SIRP a Recombinant protein therapy;
2. He has received chemotherapy, radiotherapy, biological therapy, endocrine therapy,
immunotherapy and other anti-tumor treatment within 4 weeks before the first use of
the study drug, with the exception of the following: ? nitrosourea or mitomycin C
within 6 weeks before the first use of the study drug; ? Oral fluorouracil and
small-molecule targeted drugs are 2 weeks before the first use of the study drug or
within 5 half-lives of the drug (whichever is longer); ? The systematic treatment of
traditional Chinese medicine/proprietary Chinese medicine with clear anti-tumor effect
and drugs with immunomodulatory effect (including but not limited to thymosin,
interferon, interleukin, etc.) is within 2 weeks before the first use of the study
drug;
3. Those who are participating in or have participated in the experimental drug or
medical device intervention clinical research within 4 weeks before the first
administration of this study cannot be included; In the survival follow-up stage of
the intervention study, if the time between the first administration and the end of
the previous study (the last administration) meets the above exclusion criteria, it
can be included;
4. Inoculated or planned to receive live/attenuated vaccine and mRNA vaccine within 4
weeks before screening;
5. Pregnant or lactating women;
6. AEs caused by previous anti-tumor therapy are still higher than grade 1 (based on
CTCAE v5.0) before the first administration of the study drug (except for AEs such as
hair loss and fatigue that cannot be restored to = grade 1 and will remain stable for
a long time according to the judgment of the researcher based on clinical actual
conditions, except for grade 2 peripheral neurotoxicity, and hypothyroidism stabilized
by hormone replacement therapy);
7. Those who have had = 3 levels of irAE in the past or have terminated immunotherapy due
to any level of irAE;
8. Primary central nervous system tumor, central nervous system metastasis with related
symptoms, meningeal metastasis or previous history of epilepsy should be excluded.
Patients with asymptomatic or asymptomatic central nervous system metastasis who have
been clinically controlled but have been judged stable by the researcher can be
included, but the following conditions must be met at the same time: a The disease was
stable = 4 weeks before the first administration; B. No evidence of central nervous
system disease progression was found in MRI enhancement of the head within 4 weeks
before the first administration; C. The anticonvulsant drugs have been stopped at
least 2 weeks before the first administration, and the dosage of prednisone is =
10mg/day or equivalent dose of hormone;
9. Patients who have undergone major organ surgery (excluding puncture biopsy) or had
significant trauma within 4 weeks before the first use of the study drug, or who need
to undergo elective surgery during the trial period;
10. Have a history of tissue or organ transplantation;
11. Patients with severe infection within 4 weeks before the first medication, including
but not limited to infection complications, bacteremia, severe pneumonia, etc.
requiring hospitalization; Patients with active infection before the first
administration were excluded;
12. Known history of human immunodeficiency virus (HIV) infection;
13. Active hepatitis B, untreated chronic hepatitis B or treated but uncontrolled chronic
hepatitis B (HBV DNA>200 IU/mL or>103 copies/ml);
14. Active HCV infected patients (HCV antibody positive and HCV-RNA level higher than the
lower limit of detection);
15. Untreated or under treatment tuberculosis patients, including but not limited to
tuberculosis; Those who have received standard anti-tuberculosis treatment and have
been confirmed as cured by researchers can be included;
16. Known to have a history of severe allergy, or known to have had = grade 3 allergic
reaction to macromolecular protein preparation/monoclonal antibody, and any component
of test drug;
17. Patients with active, or had a history of autoimmune diseases that may recur
(excluding vitiligo, autoimmune thyroid diseases that can be treated with hormone
replacement therapy, and type 1 diabetes patients);
18. Have received systemic glucocorticoid (prednisone>10mg/day or equivalent dose of the
same drug) or other immunosuppressive treatment within 14 days before the first use of
the study drug, except for the following cases: ? use of local, ocular,
intraarticular, intranasal and inhaled glucocorticoid treatment, ? short-term use of
glucocorticoid for preventive treatment (such as prevention of contrast agent
allergy);
19. Patients who have a history of non-infectious pneumonia requiring glucocorticoid
treatment or who currently have interstitial lung disease within 1 year before the
first administration;
20. There is a history of serious cardio-cerebrovascular disease, including but not
limited to: ? heart failure or left ventricular ejection fraction (LVEF)<50% with NYHA
grade II or above; ? There are serious cardiac rhythm or conduction abnormalities,
such as ventricular arrhythmia requiring clinical intervention, ? - ? degree
atrioventricular block, etc.; ? Acute coronary syndrome, congestive heart failure,
aortic dissection, stroke or other cardiovascular and cerebrovascular events of grade
3 or above occurred within 6 months before the first administration; ? Hypertension
that cannot be controlled clinically (this protocol is defined as that although
antihypertensive treatment is adopted, the systolic blood pressure is more than 150
mmHg and/or diastolic blood pressure is more than 100 mmHg after treatment, and has
clinical significance after evaluation by the researcher);
21. Those with the following risk of thrombosis or bleeding:
A. Myocardial infarction, unstable angina pectoris, cerebrovascular accident or
transient ischemic attack occurred within 6 months before the first administration; B.
There is a history of deep venous thrombosis, pulmonary embolism or any other serious
thromboembolism within 3 months before the first administration (implantable venous
infusion port or catheter-derived thrombosis, or superficial venous thrombosis is not
considered as "serious" thromboembolism); C. Any life-threatening bleeding event or
grade 3 or 4 gastrointestinal/variceal bleeding event requiring blood transfusion,
endoscopy or surgical treatment within 3 months before the first administration; D.
Other diseases that the researcher believes have a high risk of bleeding or thrombosis
in the future;
22. Patients who are known to have a history of abuse or drug abuse of psychotropic
substances and are considered to affect the compliance of this study;
23. Have a history of hemolytic anemia or Evans syndrome in the past 3 months;
24. In addition to the tumors at the time of study, there are other active malignant
tumors within 3 years before the first administration (not excluding locally cured
tumors, such as skin basal cell carcinoma, superficial bladder cancer cancer or breast
cancer in situ);
25. Patients with pleural effusion, pericardial effusion or ascites that are not
controlled or need drainage;
26. Patients who are not suitable for this study according to the researcher.
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