avelumab + cetuximab

Avelumab + cetuximab is an investigational combination therapy consisting of two monoclonal antibodies with complementary mechanisms of action, used in clinical trials for advanced cancers. Avelumab is an anti–programmed death-ligand 1 (PD-L1) IgG1 monoclonal antibody that blocks the interaction between PD-L1 on tumor and immune cells and its receptor PD-1, thereby preventing T-cell suppression and enhancing antitumor immune responses. Cetuximab is an anti–epidermal growth factor receptor (EGFR) IgG1 monoclonal antibody that inhibits EGFR signaling, leading to reduced tumor cell proliferation and survival, as well as increased apoptosis. Both agents can also activate innate immunity via their Fc regions by engaging natural killer (NK) cells to induce antibody-dependent cellular cytotoxicity (ADCC). The rationale for combining these drugs is based on potential synergistic effects—avelumab releases the brakes on the immune system while cetuximab stimulates it—potentially resulting in enhanced antitumor activity compared to either agent alone[2][3][8]. This combination has been studied in phase II clinical trials for diseases such as advanced cutaneous squamous cell carcinoma (cSCC), metastatic colorectal cancer (mCRC), and non-small cell lung cancer (NSCLC)[2][3][4].