Intratumoral Macrophage Exosomes With Mechanobiological R... | NCT07563972

NCT07563972

Status Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Dose Level 1: 1×10^10 Exosomes	Experimental	Intratumoral injection of mechanobiologically reprogrammed macrophage-derived exosomes at a dose of 1×10^10 exosomes per injection, administered once every 2 weeks for 4 doses (3+3 dose escalation, Cohort 1).	Biological: Mechanobiologically Reprogrammed Macrophage-Derived Exosomes (1×10^10 exosomes)
Dose Level 2: 2.5×10^10 Exosomes	Experimental	Intratumoral injection of mechanobiologically reprogrammed macrophage-derived exosomes at a dose of 2.5×10^10 exosomes per injection, administered once every 2 weeks for 4 doses (3+3 dose escalation, Cohort 2).	Biological: Mechanobiologically Reprogrammed Macrophage-Derived Exosomes (2.5×10^10 exosomes)
Dose Level 3: 5×10^10 Exosomes	Experimental	Intratumoral injection of mechanobiologically reprogrammed macrophage-derived exosomes at a dose of 5×10^10 exosomes per injection, administered once every 2 weeks for 4 doses (3+3 dose escalation, Cohort 3).	Biological: Mechanobiologically Reprogrammed Macrophage-Derived Exosomes (5×10^10 exosomes)

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Mechanobiologically Reprogrammed Macrophage-Derived Exosomes (1×10^10 exosomes)	Biological	Autologous macrophage-derived exosomes prepared from the participant's own peripheral blood monocytes. Monocytes are isolated by apheresis, differentiated into macrophages, subjected to nuclear compression via a microfluidic device to induce mechanobiological reprogramming, and then exosomes are extracted and purified by ultracentrifugation. Administered via intratumoral injection once every 2 weeks for 4 doses at a dose of 1×10^10 exosomes.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Incidence of Dose-Limiting Toxicity (DLT)	DLT is defined as treatment-related adverse events graded per NCI CTCAE v5.0 occurring during the DLT observation period, including grade ≥4 hematologic toxicity or grade ≥3 non-hematologic toxicity (with exceptions).	From first administration through Day 28 post-administration (approximately 4 weeks)

Secondary Outcomes

Measure	Description	Time Frame
Objective Response Rate (ORR)	Proportion of participants achieving complete response (CR) or partial response (PR) per RECIST v1.1 criteria	Up to 12 months
Progression-Free Survival (PFS)	Time from first administration to disease progression or death from any cause, assessed per RECIST v1.1

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Age 18 to 65 years (inclusive) at screening, any gender.
Histologically or cytologically confirmed advanced (unresectable or metastatic) solid tumors (including melanoma, soft tissue sarcoma, head and neck squamous cell carcinoma, etc.) that have failed standard therapy, have no standard treatment options, or are intolerant to standard treatment.
Must have a primary lesion suitable for local injection, accessible by direct palpation or under ultrasound/CT image guidance.
At least one measurable lesion per RECIST v1.1 criteria.
ECOG performance status score of 0-2.
Expected survival ≥ 3 months.
Adequate organ function within 7 days prior to treatment:
- Neutrophil count (NEUT#) ≥ 1.5×10^9/L; Platelets (PLT) ≥ 80×10^9/L; Hemoglobin ≥ 8 g/dL
- AST, ALT, ALP ≤ 2.5×ULN; Total bilirubin (TBIL) ≤ 1.5×ULN; Albumin ≥ 2.8 g/dL
- Serum creatinine ≤ 1.5×ULN or CCR > 60 ml/min
- INR ≤ 1.5; APTT ≤ 1.5×ULN
Voluntarily participates, signs informed consent, and is able to comply with study visits and procedures.

Exclusion Criteria:

Contraindications to intratumoral injection: inflammation or ulceration at injection site; severe bleeding tendency; abnormal or permanent body art (e.g., tattoos) at injection site interfering with local reaction observation.
History of other malignancies (except cured basal cell carcinoma, squamous cell carcinoma of skin, superficial bladder cancer, cervical carcinoma in situ, intramucosal gastrointestinal cancer without recurrence for 5 years).
Active autoimmune disease or history of autoimmune disease (including but not limited to immune-related neuropathy, multiple sclerosis, autoimmune neuropathy, Guillain-Barré syndrome, myasthenia gravis, SLE, connective tissue disease, scleroderma, IBD, autoimmune hepatitis, TEN, or Stevens-Johnson syndrome); except Type 1 diabetes on stable insulin dose.
Anti-tumor vaccine within 4 weeks before first dose; live vaccines within 4 weeks before or during the study; major surgery or severe trauma within 4 weeks before first dose.
Prior anti-tumor treatment toxicity not recovered to ≤ CTCAE v5.0 Grade 1.
Serious medical conditions: NYHA Class II or higher heart dysfunction, ischemic heart disease, significant arrhythmia, poorly controlled diabetes (fasting glucose ≥ 10 mmol/L), uncontrolled hypertension (SBP > 150 mmHg and/or DBP > 100 mmHg), LVEF < 50%, QTc > 450 ms (male) or > 470 ms (female).
Active tuberculosis or uncontrolled prior TB infection.
Hyperthyroidism or organic thyroid disease (except hypothyroidism controlled with stable thyroid hormone replacement).
Active infection or unexplained fever within 48 hours before first dose, or systemic antibiotics within 1 week before informed consent.
Active HBV (HBV DNA ≥ 2000 IU/ml or 10^4 copies/ml), active HCV (HCV antibody positive and HCV RNA above detection limit), or known HIV positive or AIDS history.
Known neurological or psychiatric disorders (e.g., epilepsy, dementia).
Known history of drug abuse or alcohol abuse within 3 months.
Pregnant or breastfeeding women; participants (or their partners) planning pregnancy or unwilling to use contraception from screening to 6 months after study completion.
Receipt of any investigational drug within 4 weeks before first dose, or concurrent enrollment in another interventional clinical study.
Any other factors judged by the investigator that may affect study completion.

PubMed Identifier	Type	Citation	Retractions
29661678	Background	Raillard M, Love EJ, Murison PJ. Effect of predosing versus slow administration of propofol on the dose required for anaesthetic induction and on physiologic variables in healthy dogs. Vet Anaesth Analg. 2018 Jul;45(4):414-422. doi: 10.1016/j.vaa.2018.02.004. Epub 2018 Mar 6.
28605571	Background	Alatrash N, Narh ES, Yadav A, Kim MJ, Janaratne T, Gabriel J, MacDonnell FM. Synthesis, DNA Cleavage Activity, Cytotoxicity, Acetylcholinesterase Inhibition, and Acute Murine Toxicity of Redox-Active Ruthenium(II) Polypyridyl Complexes. ChemMedChem. 2017 Jul 6;12(13):1055-1069. doi: 10.1002/cmdc.201700240. Epub 2017 Jun 12.