Safety and Tolerability of Au-TMP Nanoparticles in Combination With Radiotherapy for Patients With Advanced Melanoma Receiving Anti-PD-1 Therapy
Advanced melanoma is a highly aggressive malignancy that frequently exhibits resistance to conventional radiotherapy and single-agent immunotherapy. This study aims to evaluate the safety and tolerability of an innovative melanoma-specific aggregable gold nanosystem (Au-TMP) in patients with advanced melanoma. This single-arm, open-label, Phase 1a clinical trial utilizes a dose-escalation design, where participants receive a single intratumoral injection of Au-TMP followed by sequential radiotherapy and Toripalimab (anti-PD-1) treatment. This trial aims at assessing the safety of intratumoral injection of Au-TMP and radiotherapy in combination with anti-PD-1 therapy.
• Age: Age ≥ 18 years.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Histologically confirmed unresectable Stage III or Stage IV melanoma without prior systemic therapy. Prior adjuvant or neoadjuvant therapy is permitted, provided it was completed at least 3 weeks before enrollment and all related adverse events (AEs) have resolved to baseline or NCI CTCAE v5.0 Grade ≤ 1.
• Presence of at least one measurable lesion according to RECIST v1.1 criteria.
• At least one lesion suitable for intratumoral injection and radiotherapy (located in the skin, subcutaneous tissue, superficial lymph nodes, or visceral lesions assessed as safe for access) that has not received prior radiotherapy (unless documented progression has occurred).
• Adequate hematologic and organ function within 7 days prior to the first dose, including:
• Hematology: Absolute Neutrophil Count (ANC) ≥ 1.5 × 10⁹/L; Platelet count (PLT) ≥ 90 × 10⁹/L; Hemoglobin (Hb) ≥ 90 g/L. (No Granulocyte-Colony Stimulating Factor (G-CSF), platelet transfusion, or Erythropoietin (EPO)/Red Blood Cell (RBC) transfusion within 14 days prior to testing).
• Renal Function: Serum creatinine (Cr) ≤ 1.5 × Upper Limit of Normal (ULN), or calculated creatinine clearance (Ccr) ≥ 50 mL/min using the Cockcroft-Gault formula.
• Hepatic Function: Total bilirubin (TBIL) ≤ 1.5 × ULN (≤ 3.0 × ULN for patients with Gilbert's Syndrome or liver metastases); Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), and Alkaline Phosphatase (ALP) ≤ 2.5 × ULN (≤ 5.0 × ULN for patients with documented liver or bone metastases); Serum albumin ≥ 2.8 g/dL.
• Coagulation: International Normalized Ratio (INR) or Prothrombin Time (PT) and activated Partial Thromboplastin Time (aPTT) ≤ 1.5 × ULN.
• Cardiac: Left Ventricular Ejection Fraction (LVEF) ≥ 50%.
• Anticipated survival time ≥ 16 weeks.
• Agreement to use highly effective contraception methods during the trial and for 12 months after the last dose of treatment.
• Voluntarily participate in the study, sign the Informed Consent Form (ICF), demonstrate good compliance, and be willing to cooperate with follow-up.