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Penpulimab + pemetrexed is a combination chemoimmunotherapy regimen consisting of penpulimab, a humanized IgG1 monoclonal antibody targeting programmed cell death protein 1 (PD-1), and pemetrexed, a folate analog metabolic inhibitor. Penpulimab is engineered with an Fc-null backbone to eliminate Fcγ receptor binding, thereby reducing antibody-dependent cellular phagocytosis (ADCP) of activated T cells and minimizing immune-related adverse events. Pemetrexed disrupts folate-dependent metabolic processes essential for cell replication by inhibiting thymidylate synthase (TS), dihydrofolate reductase (DHFR), and glycinamide ribonucleotide formyltransferase (GARFT). This combination is primarily investigated or used as a first-line or neoadjuvant treatment for patients with advanced or resectable non-squamous non-small cell lung cancer (NSCLC), often in combination with a platinum agent (such as carboplatin or cisplatin).
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