1. Primary 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.
The patient is currently participating, or has participated in a clinical trial of an investigational drug or medical device within 4 weeks prior to the first dose of the study drug.
The patient has received any anti-tumor therapy within the past month, including but not limited to chemotherapy, radiotherapy, immunotherapy (such as anti-PD-1, anti-PD-L1, or anti-CTLA-4 antibodies, or any other antibody targeting T-cell co-regulatory pathways), etc.
The patient has received systemic corticosteroid therapy (>10 mg/kg prednisone or equivalent) within two weeks prior to the first dose, or any other form of immunosuppressive therapy.
The patient has a known history of hematologic malignancies, primary brain tumors, sarcoma, or other primary solid tumors, unless the patient has been cured and has had no evidence of recurrence for 5 years. Exceptions include cured basal cell carcinoma of the skin and carcinoma in situ of the cervix.