Advanced Solid Tumors
Conditions
Interventions
Low-dose group:Intratumoral injection of mechanically reprogrammed macrophage-derived exosomesn (1×10^10 exosomes/dose), once every 2 weeks for 4 doses.
Medium-dose group:Intratumoral injection of mechanically reprogrammed macrophage-derived exosomesn (2.5×10^10 exosomes/dose), once every 2 weeks for 4 doses.
High-dose group:Intratumoral injection of mechanically reprogrammed macrophage-derived exosomesn (5×10^10 exosomes/dose), once every 2 weeks for 4 doses.
Sponsors
West China Hospital, Sichuan University
Eligibility
Sex/Gender
All
Age
18 Years to 65 Years
Inclusion criteria
Inclusion criteria: 1. Aged 18-65 years (inclusive) at screening; either sex; 2. Patients with advanced (unresectable or metastatic) solid tumors (including melanoma, soft tissue sarcoma, head and neck squamous cell carcinoma, etc.) who have failed, are intolerant to, or have no standard treatment options; 3. Must have a primary lesion suitable for local injection — palpable subcutaneously or accessible under ultrasound/CT guidance; 4. At least one measurable lesion per RECIST 1.1; 5. ECOG performance status 0-2; 6. Estimated life expectancy =3 months; 7. Adequate organ function within 7 days before treatment: (1) Hematology: Neutrophil count (NEUT): >=1.5 x 10^9/L, Platelet count (PLT): >=80 x 10^9/L, Hemoglobin: >=8 g/dL; (2) Liver Function: Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), and Alkaline phosphatase (ALP): =2.8 g/dL; (4) Renal Function: Serum creatinine (Cr): 60 mL/min; (5) Coagulation Function: International Normalized Ratio (INR): <=1.5; Activated partial thromboplastin time (APTT): <=1.5 x ULN; 8. Willing to participate, sign the informed consent form, and comply with protocol-specified visits and procedures.
Exclusion criteria
Exclusion criteria: 1. Contraindications to intratumoral injection: (1) Inflammation or ulceration at the injection site; (2) Severe bleeding tendency, or significantly reduced platelet count or coagulation factors; (3) Any abnormality or permanent body art (e.g., tattoos) at the vaccination site that would interfere with the observation of local reactions. 2. History of other malignancies (A history of malignancies is excluded, except for: cured skin basal cell carcinoma, skin squamous cell carcinoma, superficial bladder cancer, cervical carcinoma in situ, or gastrointestinal intraepithelial carcinoma that have been cured and have not recurred for at least 5 years, or any other malignancy deemed eligible for enrollment by the Investigator); 3. Any active autoimmune disease or history of autoimmune disease, including but not limited to immune-mediated neurological disorders, multiple sclerosis, autoimmune (demyelinating) neuropathy, Guillain-Barré syndrome, myasthenia gravis, systemic lupus erythematosus (SLE), connective tissue diseases, scleroderma, inflammatory bowel disease (including Crohn's disease and ulcerative colitis), autoimmune hepatitis, toxic epidermal necrolysis (TEN), or Stevens-Johnson syndrome (with the exception of Type I diabetes mellitus managed with stable doses of insulin); 4. Prior treatments: (1) Receipt of any anti-tumor vaccine within 4 weeks prior to the first dose; (2) Use of any active vaccine against infectious diseases (e.g., influenza vaccine, varicella vaccine, etc.) within 4 weeks prior to the first dose, or planned use during the study period; (3) Undergoing major surgery or experiencing severe trauma within 4 weeks prior to the first dose; (4) Failure to recover from toxicities of prior anti-tumor therapy to = Grade 1 per CTCAE version 5.0 (with the exception of alopecia and sequelae of prior platinum-based therapy-related neuropathy) or to the levels specified in the inclusion/exclusion criteria. 5. Presence of severe medical illnesses, such as: Cardiac dysfunction = Grade II (NYHA criteria); Ischemic heart disease (e.g., myocardial infarction or angina pectoris); Clinically significant supraventricular or ventricular arrhythmias; Uncontrolled diabetes mellitus (fasting blood glucose =10 mmol/L); Uncontrolled hypertension (systolic blood pressure >150 mmHg and/or diastolic blood pressure >100 mmHg); Left ventricular ejection fraction (LVEF) 450 msec in males or >470 msec in females; Abnormal ECG findings that the Investigator considers to pose an additional risk for the investigational drug; 6. Active tuberculosis, or a history of tuberculosis infection that remains uncontrolled despite treatment, or any condition that might interfere with the detection or management of suspected drug-related pulmonary toxicity; 7. Patients with hyperthyroidism or organic thyroid disease are not eligible. Subjects with hypothyroidism treated with a stable dose of thyroid replacement hormone may be enrolled. Subjects with hypothyroidism controllable with thyroid replacement hormone (excluding immune checkpoint inhibitor-induced hypothyroidism) may be enrolled (controllability to be confirmed by the Investigator and/or an endocrinologist); 8. Presence of active infection, unexplained fever during the screening period or within 48 hours prior to the first dose, or use of systemic antibiotics within 1 week prior to signing the informed consent form; 9. Active Hepatitis B (HBV DNA =2000 IU/ml or 104 co
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence of dose-limiting toxicity (DLT);Incidence and severity of adverse events and serious adverse events; | — |
Secondary
| Measure | Time frame |
|---|---|
| Objective response rate (ORR);Progression-free survival (PFS);Overall survival (OS); | — |
Countries
China
Contacts
Public ContactPeng, xingchen
West China Hospital, Sichuan University
Outcome results
None listed