Evaluate the Safety and Efficacy of Autologous Tumor-infiltrating Lymphocyte in Patients With Refractory Melanoma Who Failed to Immune Checkpoint Inhibitors

Prior treatment

• History of active or latent tuberculosis infection within 1 year prior to screening (except for those declared cured after treatment).
• Uncontrolled central nervous system (CNS) metastases (note: patients with treated and stable brain metastases for ≥30 days prior to screening are eligible).
• Any surgery, radiotherapy, or systemic anticancer therapy within 3 weeks prior to CT-SP administration.
• Participation in another interventional clinical trial and receipt of any investigational drug within 3 weeks prior to CT-SP administration.
• Unresolved toxicity from prior therapy not recovered to Grade ≤1 (per NCI CTCAE v5.0), except for clinically non-significant events such as alopecia.
• Receipt of systemic immunosuppressive therapy (including corticosteroids) within 10 days prior to tumor tissue collection for CT-SP manufacturing (exceptions: local/inhaled steroids; systemic corticosteroids ≤ prednisolone 20 mg/day equivalent may be permitted at investigator discretion).
• Clinically significant cardiovascular disease, including but not limited to:
  • Uncontrolled hypertension (systolic BP \> 180 mmHg and/or diastolic BP \> 100 mmHg), Unstable angina, Pulmonary embolism, Cerebrovascular accident, Valvular heart disease, Congestive heart failure (NYHA Class III or IV), Myocardial infarction or significant arrhythmia within 24 weeks prior to screening

Other illness

• History of solid organ transplantation.
• Diagnosis of another malignancy within the past 5 years, except for adequately treated basal cell carcinoma, squamous cell carcinoma of the skin, or non-invasive cervical cancer.
• Positive test for anti-HIV antibodies.
• Active HBV or HCV infection considered clinically inappropriate for study participation by the investigator.
• Other serious comorbid medical conditions that may interfere with study participation, as determined by the investigator.
• Active or severe infection requiring hospitalization or intravenous antibiotics, deemed unsuitable for participation by the investigator.
• Significant psychiatric illness that, in the investigator's opinion, may affect subject compliance or study conduct.
• Subjects with autoimmune or inflammatory disorders, where the investigator deems abnormal autoantibody test results to be clinically relevant.
• Any other condition not listed above that the investigator considers to make the subject ineligible for participation.

Lab values

• Known hypersensitivity or contraindication to: Cyclophosphamide, Fludarabine, Interleukin-2 (IL-2), CT-SP excipients: 5% human serum albumin, sterile saline, 5% DMSO

Other

• Pregnant or breastfeeding women.
• Known contraindications to dopamine or other pressor agents.
• Subjects determined to be unsuitable for participation based on the anticipated manufacturing timeline and logistics of CT-SP.

• Age ≥19 and ≤80 years at the time of informed consent.
• Histologically or cytologically confirmed melanoma, classified as refractory/unresponsive Stage IIIc or IV after failure of prior immune checkpoint inhibitor therapy.
• At least one measurable and evaluable lesion as defined by RECIST version 1.1.
• ECOG performance status of 0 or 1.
• Estimated life expectancy ≥12 weeks.
• Ability to undergo tumor tissue biopsy for the purpose of producing a sufficient quantity of autologous tumor-infiltrating lymphocytes (CT-SP).
  • Willingness to undergo tissue collection procedures after enrollment in the study.
  • For surgical specimens: at least one lesion with a minimum diameter of 1 cm. For biopsy samples: a minimum of 20-25 tissue fragments must be obtainable.
• Adequate organ function as defined by the following laboratory values (up to two retests permitted; transfusions or medical correction allowed):
  • Hemoglobin ≥ 9.0 g/dL
  • Absolute Neutrophil Count (ANC) ≥ 1,500/μL
  • Absolute Lymphocyte Count (ALC) ≥ 500/μL
  • Platelet count ≥ 100,000/μL
  • Serum creatinine clearance (estimated by Cockcroft-Gault) ≥ 50 mL/min
  • Total bilirubin ≤ 2.0 mg/dL
  • AST and/or ALT ≤ 3 × ULN (≤ 5 × ULN if liver metastasis is present)
• Subjects of childbearing potential must agree to use acceptable contraceptive methods during the study, including but not limited to:
  • Complete abstinence, Sterilization (patient or partner), Intrauterine device, Hormonal contraception, Barrier methods (e.g., condom + spermicide, diaphragm)
• Written informed consent voluntarily provided before any study-specific procedures are conducted.