Immunotherapy with PD-1/PD-L1 inhibitors is the standard method of care for the treatment of newly diagnosed advanced or metastatic NSCLC, with or without chemotherapy. Many tumors, however, develop resistance to these immunotherapy agents. There is a need to develop more effective therapies for patients with metastatic NSCLC in the second-line setting and beyond. In this review, we present an overview of novel immunotherapies being investigated regarding the treatment of these patients. We summarize completed, as well as ongoing, trials investigating these therapies as monotherapy or in combination with PD-1/PD-L1 inhibitors. These include immune co-stimulatory antibodies, T-cell agonists, oncolytic viruses, vaccines, TIL therapies, and CAR-T therapies.
Keywords: immunotherapy; resistance; trials.