Clinical Study of SM3321 With Solid Tumors

Inclusion Criteria:

1. Male or female aged 18 years or older.
2. Subjects with histologically or cytologically confirmed unrespectable locally advancedor metastatic solid tumors.
3. The subject's disease progresses after receiving adequate standard treatment or isintolerant to standard treatment or has no effective standard treatment optionsavailable.
4. Subjects in this study must have at least one evaluable lesion (based on RECIST v1.1).
5. Expected survival ≥12 weeks
6. ECOG PS score 0-2 points
7. The function of the major organs is basically normal, and the laboratory examinationwithin 7 days or less before the first administration meets the following standards: a) Liver function:

• AST/ALT ≤ 2.5 × ULN (ULN= upper limit of normal);If liver metastasis occurs,AST/ALT≤5×ULN;
• Serum total bilirubin ≤ 1.5 × ULN;Or in cases of Gilbert syndrome ≤3×ULN; b)Blood routine (no hematopoietic growth factor or blood transfusion was usedwithin 2 weeks before enrollment) :
• Hemoglobin ≥ 90 g/L;
• Platelet count ≥100×10^9/L;
• Absolute neutrophil count ≥1.5×10^9/L. c) Kidney function:
• Creatinine clearance ≥50 mL/min (calculated by Cockcroft-Gault formula). d)Coagulation function:
• International normalized ratio (INR) ≤1.5×ULN.

8. Female subjects of reproductive age must have a negative blood pregnancy test within 3days prior to the first use of the study drug; Eligible subjects (men and women) whoare fertile (defined as sexually mature and biologically fertile) must agree to use areliable contraceptive method (hormonal or barrier method or abstinence, etc.) withtheir partner during the study period and for at least 6 months after the last dose.
9. Willing to participate in clinical research, understand and sign informed consent, andfollow up and abide by research procedures on time.

Exclusion Criteria:

1. Known allergy to SM3321 or its formulation components.
2. Previously received the following anti-tumor therapy:
3. Chemotherapy, targeted therapy, immunotherapy, or other anticancer therapy within 28 days or 5 half-lives (whichever is shorter) prior to initial administration ofthe investigational therapy, except for the following:

• anti-programmed death receptor-1 / programmed death receptor-ligand 1antibodies used within 1.5 months;
• nitrosourea or mitomycin eluting period ≤6 weeks;
• Washout period of fluoropyrimidine or small molecule targeted drugs ≤5half-lives or 2 weeks (whichever is longer);
• The washout period for herbal treatments with anticancer indications is ≤2weeks.

2. Radiotherapy received within 4 weeks prior to the first dosing of the studytreatment, allowing a single fractionated radiotherapy for symptom relief.
3. The subject has participated in any other clinical study and received the trialdrug within 28 days prior to the first administration of the study drug.
4. Major surgery within 28 days before dosing or major surgery expected during the studyperiod.
5. There was acute toxicity from prior antitumor therapy that had not returned to ≤ grade 1 or baseline levels specified by the inclusion criteria prior to first administration (based on NCI-CTCAE v5.0).
6. Uncontrolled or severe cardiovascular disease, including but not limited to any of thefollowing:
7. Prolonged QTc (using Fridericia's correction formula), male >450 ms/ female >470ms, or congenital long QT syndrome;
8. Left ventricular ejection fraction (LVEF) <50% was assessed by Multiple-gatedacquisition (MUGA) or ECHO;
9. any of the following in the 6 months prior to screening: > Grade 2 ventriculararrhythmia, severe/unstable angina, congestive heart failure (New York heartassociation (NYHA) III orGrade IV), coronary artery bypass grafting, myocardialinfarction, cerebrovascular accident, or transient ischemic attack;
10. Uncontrolled hypertension (systolic blood pressure >160 mmHg or diastolic bloodpressure >100 mmHg).If blood pressure can be controlled within the above limitsby antihypertensive therapy, subjects with a history of hypertension will beadmitted to the study.,
11. Concurrent history of severe chronic or active infection:
12. The subject has active hepatitis B, defined as:If HepatitisB surface antigen (HBsAg) is positive, hepatitisB virus (HBV) Deoxyribonucleic acid (DNA) should betested for HepatitisB virus (HBV).HBV DNA was higher than the lower limit ofquantitative value.
13. The subject has active Hepatitis C, defined as: if Hepatitis C virus (HCV)antibodies are positive, HCV Ribonucleic acid (RNA) should be tested, and HCVRNAis positive;
14. Known to have Acquired immune deficiency syndrome (AIDS) or Humanimmunodeficiency viru (Human immunodeficiency viru)Hiv-infected subjects may beeligible for study participation if the CD4+ T cell count is ≥350 cells /µL andthere is no history of opportunistic infection as defined by AIDS.
15. other severe chronic infections, including but not limited to hospitalization forinfectious complications, bacteremia, severe pneumonia, or active tuberculosiscomplications, within 4 weeks prior to initial administration of SM3321;Or anuncontrolled active infection or unexplained fever >38 ° C occurred within 7 daysprior to first administration of SM3321.
16. Uncontrolled co-morbidities such as:
17. Subjects with known active primary tumors or metastases of the Central nervoussystem (CNS);Note: Subjects with previously treated primary CNS tumors/metastasesmay participate in the study, provided that they are clinically stable for atleast 2 weeks, have no evidence of new BMS or BMS enlargement, and were firstdosed with SM3321 The steroid dose was not increased during the first 14 days tomanage CNS symptoms.Subjects with cancerous meningitis or pia spread or spinalcord compression were excluded from this study even if clinically stable.
18. known to have other malignancies that are currently advanced or have requiredaggressive treatment within the past 5 years (except for non-melanoma skin basalcell carcinoma or squamous cell carcinoma, breast/cervical carcinoma in situ,superficial bladder carcinoma and other in situ cancers that have been treatedradically and have no evidence of disease recurrence);
19. A history of symptomatic deep vein thrombosis or pulmonary embolism within 6months prior to enrollment;
20. Significant malnutrition, such as the need for intravenous nutritional solutions.Patients with stable malnutrition for more than 4 weeks after correction beforethe first dose of the study drug could be enrolled;
21. Other acute or chronic medical conditions or abnormalities in laboratory testingthat may increase the risks associated with participation in the study or use ofthe study product, or interfere with the interpretation of the study results and,in the judgment of the investigator, render the subject ineligible forparticipation in the study.
22. Pregnant or lactating women.
23. Have a history of active autoimmune disease, such as systemic lupus erythematosus,rheumatoid arthritis, vasculitis, or have received long-term systemic steroid therapy (at doses greater than 10 mg prednisone daily equivalent) or any other form ofimmunosuppressive therapy within 14 days prior to the first administration of thestudy drug. Exceptions include: clinically stable autoimmune thyroid disease; Receiveinhaled or topical corticosteroid therapy, such as intraocular, intraarticular, andintranasal administration of prednisone equivalent ≤10 mg daily; Short-term use ofcorticosteroids (no more than 7 days) for preventive treatment (for example, toprevent hypersensitivity to contrast agents or non-autoimmune allergic diseases);Aswell as replacement therapy (e.g., thyroxine for hypothyroidism, insulin for diabetes,physiocorticoid replacement for adrenal or pituitary insufficiency).
24. Known history of allogeneic organ transplantation and allogeneic hematopoietic stemcell transplantation.
25. Received systemic immunomodulatory drugs, such as thymosin, IL-2, and IFN, within 14days prior to the first administration of the study drug.
26. People who have a clear history of mental disorders and take medication for treatment.
27. People with a history of drug abuse or use.
28. Receive or will receive live vaccine within 30 days prior to the first dose of thestudy drug, or plan to receive any live vaccine during the study.
29. The Investigator believes that the subject may have other factors that could affectthe study results and interfere with the subject's participation in the overall studyprocess, including previous or existing medical conditions, abnormal treatments orlaboratory tests, and the subject's unwillingness to comply with all procedures, studyrestrictions and requirements.