This study evaluates the combination of the autophagy inhibitor hydroxychloroquine (HCQ), the MEK inhibitor tunlametinib, and the anti-PD-1 antibody pucotenlimab in patients with locally advanced or metastatic melanoma. The primary objectives are to assess the objective response rate (ORR) and progression-free survival (PFS). Secondary objectives include evaluating adverse events (type, severity, and incidence), duration of response (DOR), disease control rate (DCR), and overall survival (OS), as well as exploring the molecular mechanisms by which autophagy modulation enhances immunogenicity in mutant melanoma. Further exploratory analyses will examine the mechanisms by which autophagy inhibition enhances tumor sensitivity to PD-1 blockade, thereby establishing experimental and theoretical grounds for refining future clinical approaches.
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Comparing Tunlametinib Capsules and Combination Chemotherapy in Advanced NRAS-mutant Melanoma
Tunlametinib Combination Therapy in KRAS-Mutated Unresectable Locally Advanced or Metastatic Non-Small Cell Lung Cancer
Phase II Trial of Tunlametinib in Patients With NRAS Mutant Non-melanoma Refractory Solid Tumors
Efficacy of Tunlametinib in Combination With Anti-EGFR Monoclonal Antibody in Patients With RAS-Mutated Advanced Gastrointestinal Malignancies
A Prospective, Single-Arm, Phase II Clinical Study of Neoadjuvant Therapy With Pucotenlimab, Lenvatinib, and Temozolomide for Resectable Head and Neck Mucosal Melanoma (PLT-NAT-HNMM-II)