avelumab + pembrolizumab + enfortumab vedotin

This is a combination regimen of three drugs: **avelumab**, **pembrolizumab**, and **enfortumab vedotin**. - **Avelumab** is a fully human IgG1 monoclonal antibody that targets programmed death-ligand 1 (**PD-L1**), blocking its interaction with PD-1 and B7.1 receptors and thereby restoring antitumor immune responses. - **Pembrolizumab** is a monoclonal antibody that inhibits **PD-1** (programmed death-1) receptor on T-cells, preventing PD-L1 and PD-L2 mediated immune evasion by tumor cells, enabling T-cell mediated cytotoxicity. - **Enfortumab vedotin** is an **antibody-drug conjugate (ADC)** composed of a human monoclonal antibody targeting **Nectin-4**, conjugated via a protease-cleavable linker to monomethyl auristatin E (**MMAE**), a microtubule-disrupting cytotoxic agent. Upon binding to Nectin-4-expressing tumor cells, it is internalized, MMAE is released intracellularly, causing cell cycle arrest, apoptosis, and immunogenic cell death. This combination may offer complementary antitumor activity by maximizing immune checkpoint blockade (PD-1, PD-L1) and direct tumor cell killing through targeted delivery of cytotoxic payload, potentially enhancing tumor regression beyond standard therapies. The combination is under clinical development and not an approved standard regimen; however, dual combinations (enfortumab vedotin plus pembrolizumab) are approved and in active clinical use [[3]][[9]].