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Simvastatin + nivolumab + oxaliplatin is a combination therapy regimen under investigation for the first-line treatment of HER2-negative, ARID1A-mutated advanced gastrooesophageal carcinoma. This regimen, evaluated in the ARES Phase 2 trial sponsored by the National Cancer Institute, Naples, combines the HMG-CoA reductase inhibitor simvastatin with the PD-1-targeting monoclonal antibody nivolumab and a standard oxaliplatin-based chemotherapy backbone (such as mFOLFOX6 or XELOX). The rationale for this combination is based on evidence that ARID1A mutations may create metabolic vulnerabilities or immune-modulating effects that are enhanced by statins, potentially improving the efficacy of standard chemo-immunotherapy.
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