A Phase I Platform Study of Target-Based Screened CAR-Macrophages for the Treatment of Advanced Malignant Tumors

Exclusion Criteria

• •Known hypersensitivity to CAR-M or any of its excipients.
• •History of severe hypersensitivity to filgrastim (G-CSF) or tocilizumab.
• •Known history of substance abuse.
• •A history of ≥ Grade 3 immune-related adverse events (irAEs) or ≥ Grade 2 immune-related myocarditis following prior immunotherapy.
• •Active infection requiring systemic therapy, except for the following conditions: uncomplicated urinary tract infection (UTI) (afebrile and resolved after 3 days of antibiotic therapy) or bacterial pharyngitis (confirmed by GAS testing and treated with appropriate antibiotics).
• •HIV infection, active hepatitis B virus (HBV) infection (HBV DNA \> upper limit of normal \[ULN\]), or active hepatitis C virus (HCV) infection (HCV RNA \> ULN).
• •History of malignant neoplasm other than the following within the past 5 years:
• •Curable malignant neoplasms (e.g., basal cell carcinoma, carcinoma in situ of the cervix/breast, or cutaneous squamous cell carcinoma).
• •Malignant neoplasms with a favorable prognosis (e.g., papillary thyroid carcinoma, carcinoma in situ of the skin or breast), regardless of whether they have been cured or not.
• •Receipt of other investigational drugs or therapies within 4 weeks prior to the first administration of CAR-M, or ongoing participation in the safety follow-up period of other investigational drugs or therapies.
• •Presence of severe, non-healing wounds, ulcers, or fractures within 4 weeks prior to the first administration of CAR-M.
• •History of substance abuse or psychiatric disorders.
• •History of severe cardiovascular and cerebrovascular diseases, including but not limited to:
• •Acute events: myocardial infarction, stroke, or New York Heart Association (NYHA) Class III-IV heart failure within 6 months.
• •Thromboembolism: symptomatic deep vein thrombosis or pulmonary embolism (DVT/PE) within 6 months (unless on stable anticoagulant therapy).
• •Arrhythmia: ventricular arrhythmia requiring intervention or Grade II-III atrioventricular block.
• •Confirmed pulmonary fibrosis, interstitial pneumonitis, pneumoconiosis, radiation pneumonitis, or severe pulmonary dysfunction.
• •For patients with prior treatment: ≥ Grade 2 hematological toxicity or ≥ Grade 3 non-hematological toxicity per the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0, except for toxicities deemed to pose no safety risk by the investigator (e.g., alopecia, Grade 2 peripheral neuropathy).
• •Indwelling catheters/drainage tubes (excluding central venous catheters).
• •Central nervous system (CNS) disorders: epilepsy, stroke, dementia, or autoimmune diseases involving the CNS.
• •Active or untreated brain or CNS disorders, including brain metastases that have not stabilized for ≥ 8 weeks after radiotherapy, symptomatic brain metastases, or cytologically confirmed carcinomatous meningitis.
• •Severe immunodeficiency.
• •History of prior transplantation: allogeneic stem cell transplantation or solid organ transplantation.
• •Active autoimmune disease requiring systemic immunosuppression (prednisone dose \> 10 mg/day or equivalent).
• •History of high-risk autoimmune diseases with potential for recurrence (e.g., systemic lupus erythematosus \[SLE\], rheumatoid arthritis \[RA\], inflammatory bowel disease \[IBD\]). Exceptions: stable vitiligo/psoriasis, hormone-replaced hypothyroidism, or well-controlled Type 1 diabetes mellitus (HbA1c ≤ 7%).
• •Use of systemic glucocorticoids (prednisone \> 10 mg/day) or other immunosuppressants within 14 days (exceptions: topical/inhaled steroids, adrenal replacement therapy).
• •Receipt of major organ surgery, severe trauma, or invasive dental procedures (e.g., tooth extraction, dental implantation) within 4 weeks prior to the first administration of CAR-M, or planned elective surgery during the study period.
• •Active autoimmune disease or history of recurrent autoimmune disease (excluding well-controlled Type 1 diabetes mellitus; hypothyroidism manageable with hormone replacement therapy alone; or dermatological conditions not requiring systemic therapy, e.g., vitiligo or psoriasis).
• •Presence of active infection requiring systemic anti-infective therapy.
• •Positive pregnancy test in women of childbearing potential (WOCBP).
• •Refusal to use effective contraceptive measures from the time of informed consent until 1 year after treatment.