Tunlametinib in Combination With Pucotenlimab and Hydroxychloroquine in NRAS Mutant Melanoma

Inclusion Criteria: * Age ≥ 18 years of age, both genders. * Subjects with unresectable or metastatic melanoma (Stage III/IV) confirmed by histology or cytology * The mutated NRAS genes were confirmed by sequencing. * Prior systemic antineoplastic therapy is allowed. All acute toxic effects of prior antitumor therapy must have resolved to grade 1 or lower before the start of the study drug, with the exception of alopecia (grade 1 or 2 permitted), neurotoxicity (grade 1 or 2 permitted), or bone marrow parameters (grade 1, 2, or 3 permitted). * ECOG, 0-2. * The life expectance should be at least 12 months. * Eligible subjects had not received chemotherapy for locally advanced or metastatic disease and had at least one measurable lesion according to the Response Evaluation Criteria in Solid Tumors (RECIST 1.1 criteria). * To ensure eligibility, the following criteria must be met regarding major organ and bone marrow functions: Adequate bone marrow function: absolute neutrophil count (ANC)≥ 1.5\^109/L, platelet count (PLT)≥ 100\^109/L, and hemoglobin level (HB)≥ 9 g/dL (no transfusion received within 14 days). Serum total bilirubin (TBIL) must be ≤ 1.5 times the upper limit of normal (ULN). Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 times the upper limits of normal, serum creatinine ≤1.5, and Creatinine clearance had to be greater than 50 mL/min. Creatinine clearance, as an estimate of glomerular filtration rate (eGFR), was calculated according to t…