avelumab + lorlatinib

Avelumab + lorlatinib is an investigational combination therapy consisting of avelumab, a human anti–PD-L1 monoclonal antibody immune checkpoint inhibitor, and lorlatinib, a next-generation small molecule ALK tyrosine kinase inhibitor. This combination has been studied primarily in patients with ALK-positive advanced non–small cell lung cancer (NSCLC). Avelumab works by blocking the interaction between PD-L1 and its receptors (PD-1 and B7.1), thereby enhancing T-cell mediated antitumor immune responses. Lorlatinib inhibits ALK and ROS1 tyrosine kinases, including resistant mutations, to block oncogenic signaling pathways that drive tumor growth. The JAVELIN Lung 101 phase 1b/2 trial demonstrated that this combination was feasible in ALK-positive NSCLC patients with manageable toxicity and promising objective response rates[1][2][3].