Safety and Efficacy of NK510 to Treat Osteosarcoma and Soft Tissue Sarcoma

Inclusion Criteria:

• signed informed consent obtained,can be followed upon protocol;
• age ≥ 10 years;
• histopathologically confirmed diagnosis of advanced metastatic osteosarcoma ornon-specific soft tissue sarcoma;
• Subjects for dose-escalation studies: failed to at least one chemotherapy regimen andundergoing disease progression or untolerable drug toxicity before enrollment;Subjectsfor postoperative adjuvant therapy study: radical surgery within 3 months before thefirst infusion of NK510 and no local recurrence or distant metastasis;
• according to RECIST 1.1,Recurrent and refractory patients have at least one measurablelesion at baseline. Patients receiving adjuvant treatment after radical surgery haveno measurable lesions on imaging examination;
• ECOG physical status score of 0 or 1;
• Expected survival >=12 weeks;
• Female subjects of childbearing age or male subjects whose sexual partners are femalesubjects of childbearing age are required to take effective contraceptive measuresthroughout the entire treatment period and 6 months after the treatment period;
• good organ and bone marrow hematopoietic function, the laboratory test values within 7days before enrollment meet the following requirements (no medication for bloodcomponents, cell growth factors, or albumin correction treatment is allowed within thefirst 14 days of obtaining laboratory test), as follows:

1. Hematological:Neutrophil count ≥1.5×10^9/L; Platelet count ≥ 75×10^9/L;Hemoglobin ≥ 9 g/dL;
2. Hepatic:Total bilirubin ≤1.5 x ULN;ALT and AST≤2.5×ULN;Albumin ≥ 28 g/L; Alkalinephosphatase ≤ 5 × ULN;
3. Renal:Serum creatinine ≤ 1.25 × ULN or creatinine clearance ≥ 50mL/min (CockcroftFault formula);Patients whose urine routine results show urinary protein<2+orwhose baseline urine routine test shows urinary protein ≥ 2+will undergo 24-hoururine collection with a 24-hour urine protein quantification of<1g.
4. Coagulation:International standardized ratio (INR) ≤ 2, and activated partialthromboplastin time ≤ 1.5 × ULN.

Exclusion Criteria:

• Have received local or systemic anti-tumor treatment within 4 weeks before the firstadministration of NK510(Chinese medicine or traditional Chinese patent medicines andsimple preparations is 2 weeks before administration);
• Untreated active hepatitis B (HbsAg positive and peripheral blood HBV-DNA>1000 IU/ml);Hepatitis C virus antibody positive;
• Patients with central nervous system metastasis;
• Previous history of arterial and venous thromboembolism events, including myocardialinfarction, unstable angina, cerebrovascular accident or transient ischemic attack,pulmonary embolism, deep vein thrombosis, or any other serious thromboembolism within 6 month before NK510 first infusion;
• Severe bleeding tendency or coagulation dysfunction, or undergoing thrombolytictherapy;
• Uncontrolled hypertension, with systolic blood pressure ≥ 150mmHg or diastolic bloodpressure ≥ 100mmHg after optimal medical treatment, hypertension crisis or history ofhypertensive encephalopathy;
• Symptomatic congestive heart failure (New York Heart Association classificationII-IV). Symptomatic or poorly controlled arrhythmia. The QT interval is prolonged,with QTc>450ms for males and 470ms for females. The echocardiography shows that theleft ventricular ejection fraction at rest is less than 50%;
• Active pulmonary tuberculosis (TB), who is receiving anti-tuberculosis treatment orhas received anti-tuberculosis treatment within one year before the first studymedication;
• People infected with human immunodeficiency virus (HIV), known as active syphiliscarriers;
• Severe infections that are active or poorly controlled clinically. Severe infectionwithin 4 weeks prior to initial administration, including but not limited tohospitalization due to complications such as infection, bacteremia, or severepneumonia;
• Administer therapeutic antibiotics orally or intravenously within one week beforestarting the study treatment;
• Active autoimmune diseases requiring systemic treatment have occurred within 2 yearsprior to the first administration. Allow the use of alternative therapies (such asthyroxine, insulin, or physiological corticosteroids for adrenal or pituitaryinsufficiency). A known history of primary immunodeficiency;
• Within 4 weeks before the first administration, immunosuppressive drugs have beenused, excluding local corticosteroids administered through nasal spray, inhalation, orother means, or systemic corticosteroids administered in physiological doses (i.e. nomore than 10 mg/day of prednisone equivalent dose). Temporary use of corticosteroidsis allowed for the prevention of allergic reactions or the treatment of respiratorydistress symptoms such as asthma and chronic obstructive pulmonary disease;
• Within 4 weeks before the first administration or planned to receive live attenuatedvaccines during the study period;
• Uncontrolled/uncorrectable metabolic disorders or other non malignant tumor organdiseases or systemic diseases or secondary reactions to cancer, which can lead to highmedical risk and/or uncertainty in survival evaluation;
• Other acute or chronic diseases, mental illnesses, or abnormal laboratory test valuesthat may lead to increased risk of study participation or drug administration, orinterference with the interpretation of study results, based on the judgment of theinvestigator, the patient is not eligible to participate in this study;
• Diagnosed as other malignant tumors within 5 years prior to the first administration,excluding basal cell carcinoma of the skin, squamous cell carcinoma of the skin,and/or carcinoma in situ after radical resection;
• Those who have participated in clinical trials of other drugs and received treatmentwith investigational drugs within 4 weeks before the first administration;
• Within 2 weeks before the first administration, medication with immunomodulatoryeffects (including thymosin, interferon, interleukin, except for local use to controlpleural or ascites) has been received;
• Pregnant or lactating female patients.