CD70-Targeted CAR-T Therapy in CD70-Positive Advanced Solid Tumors

Korábbi kezelés

• Prior treatment with anti-CD70 therapies;
• Active/symptomatic central nervous system (CNS) metastasis or meningeal metastasis: Subjects with treated brain metastases are eligible if treatment was completed ≥4 weeks prior to screening and there is no evidence of progression on imaging;
• Prior treatments within specified time frames:
  • Participation in other interventional clinical trials within 3 months before cell infusion (for unapproved drugs, the last dose must be ≥3 months prior; for approved drugs, ≥5 half-lives prior to cell infusion);
  • Received chemotherapy or targeted therapy within 2 weeks prior to blood collection or within 5 half-lives of the drug (whichever is shorter);
  • Received >10mg/day prednisone (or equivalent) within 2 weeks prior to blood collection, unless for adrenal replacement or inhaled/local steroids (except for active autoimmune disease);
  • Received live attenuated vaccines within 4 weeks prior to screening;
• Active infection requiring systemic treatment or uncontrolled infection within 1 week before screening;
• History of any other malignancy within the past 3 years, except for treated and stable non-melanoma skin cancer or malignancies treated with curative intent and no evidence of active disease for ≥3 years;
• Cardiovascular conditions:
  • NYHA Class III or IV heart failure;
  • Myocardial infarction or coronary artery bypass graft (CABG) within 6 months prior to screening;
  • Clinically significant ventricular arrhythmias or unexplained syncope (excluding vasovagal or dehydration);
  • Severe non-ischemic cardiomyopathy;
• Toxicity from prior anti-tumor treatments has not resolved to baseline or ≤grade 1, except for alopecia or peripheral neuropathy;

Más betegség

• Active or uncontrolled autoimmune diseases such as Crohn's disease, rheumatoid arthritis, systemic lupus erythematosus, systemic vasculitis, etc.;
• Positive for HBsAg or HBcAb with elevated HBV DNA in peripheral blood; positive for HCV antibodies with detectable HCV RNA levels; positive for HIV antibodies; positive syphilis test;
• History of venous thromboembolism (e.g., pulmonary embolism) requiring ongoing anticoagulation treatment, or meeting one of the following criteria:
  • Severe bleeding (grade 3 or 4) lasting for ≥30 days;
  • Post-thrombotic sequelae (e.g., persistent dyspnea and hypoxia) due to venous thromboembolism;
• Other conditions that, in the opinion of the investigator, make the subject unsuitable for participation in the trial.

Egyéb

• Pregnant or breastfeeding women;

• Age ≥18 years, regardless of gender;
• Histologically or cytologically confirmed advanced/metastatic solid tumors (tumors with positive CD70 expression, confirmed histopathological ly with IHC 3+ score);
• Failed or intolerant to standard second-line treatments (at least one of the following: tyrosine kinase inhibitors (TKIs), poly(ADP-ribose) polymerase inhibitors (PARPi), anti-angiogenic therapy; disease progression or inability to tolerate surgery, chemotherapy, radiotherapy, or targeted therapy);
• At least one measurable lesion per RECIST 1.1 criteria, with measurable lesions defined as:
  • Extranodal lesions with a long axis ≥10mm on CT scan;
  • Lymph node lesions with a short axis ≥15mm on CT scan;
  • CT slice thickness ≤5mm.
• ECOG performance status of 0-2 ;
• Expected survival ≥12 weeks;
• No history of severe psychiatric disorders;
• Adequate organ function as defined by the following:
  • Hematology: White blood cell count >2.0×10⁹/L, neutrophils >0.8×10⁹/L, lymphocytes >0.5×10⁹/L, platelets >50×10⁹/L, hemoglobin >90g/L;
  • Cardiac: Echocardiogram showing left ventricular ejection fraction (LVEF) ≥50%, and ECG with no significant abnormalities;
  • Renal: Serum creatinine ≤2.0×ULN;
  • Hepatic: ALT and AST ≤3.0×ULN (may be relaxed to ≤5.0×ULN in cases with liver tumor infiltration); total bilirubin ≤2.0×ULN (may be relaxed to ≤3.0×ULN in cases with Gilbert's syndrome or liver tumor infiltration);
  • Oxygen saturation ≥92% without supplemental oxygen;
• Ability to undergo single or venous blood collection, with no contraindications to cellular collection;
• Female subjects must agree to use reliable contraception (excluding fertility awareness methods) from the time of informed consent until 1 year after CAR-T cell infusion;
• Subject or authorized guardian agrees to participate in the trial and signs the informed consent form (ICF), indicating understanding of the trial's purpose and procedures and willingness to participate.