A Randomized, Double-Blind, Single-Center, Exploratory Study With Parallel Controls on the Safety and Efficacy of Neoadjuvant Low Branched-Chain Amino Acid Diet in Combination With Anti-PD-1 Monoclonal Antibody for Stage III Melanoma
Objective: To evaluate the safety of a low branched-chain amino acid diet (60% of the normal dietary BCAA content) combined with anti-PD-1 monoclonal antibody as neoadjuvant therapy in patients with stage III melanoma, by documenting the incidence of all adverse events (AEs) and serious adverse events (SAEs), and analyzing changes from baseline in physical examinations, vital signs, and laboratory test results. 2. Secondary
Objectives: To assess the pathological response rates (including pCR, near-pCR, pPR, and pNR) of the combination therapy in stage III melanoma; to evaluate the objective response rate (ORR) according to the Response Evaluation Criteria in Solid Tumors (RECIST v1.1) and the immune-related RECIST (irRECIST) criteria; and to estimate event-free survival (EFS) and overall survival (OS) through long-term follow-up. 3. Exploratory Objectives: To investigate the quality of life (QoL) in patients receiving the low BCAA diet combined with anti-PD-1 therapy; and to identify predictive biomarkers for treatment outcome differences, such as immune-related gene signatures (e.g., PD-L1 expression) and driver gene mutations in somatic variants.
• Patients with histopathologically or cytologically confirmed Stage III malignant melanoma. Stage III is defined as the presence of at least one clinically accessible lymph node metastasis or in-transit metastasis. Patients with mucosal or ocular melanoma are excluded; those with melanoma of unknown primary are also excluded.
• No prior radiotherapy or systemic chemotherapy. No treatment with anti-PD-1, anti-PD-L1, anti-PD-L2 monoclonal antibodies, anti-CTLA-4 monoclonal antibody, interferon (IFN), or targeted agents within the last month.
• Life expectancy ≥ 6 months.
• At least one measurable lesion as defined by RECIST version 1.1.
• Patients must have provided written informed consent to participate voluntarily in this trial and must be between 18 and 75 years of age on the day of signing the consent form.
• ECOG (Eastern Cooperative Oncology Group) performance status score of 0 or 1.
• Adequate organ function as assessed by the following laboratory values (within 4 weeks prior to the start of study drug treatment):
‣ Absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L
⁃ Platelets ≥ 100 × 10⁹/L
⁃ Hemoglobin ≥ 90 g/L (no transfusion within 14 days prior to enrollment)
⁃ Serum creatinine ≤ 1.5 × upper limit of normal (ULN)
⁃ Serum total bilirubin ≤ 1.5 × ULN
⁃ AST (SGOT) and ALT (SGPT) ≤ 2.5 × ULN or ≤ 5 × ULN (for patients with liver metastases)
⁃ Prothrombin time (PT)/International Normalized Ratio (INR) and activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN (unless the patient is on anticoagulant therapy, in which case PT or aPTT must be within the therapeutic range intended for the anticoagulant).
• For women of childbearing potential, a negative urine or serum pregnancy test within 7 days prior to receiving the first dose of the study drug.
• Female patients of childbearing potential who enroll in the study must be willing to use adequate contraception for up to 12 months after the last dose of the study drug.