Addressing Unmet Need in Second-Line NSCLC Without Actionable Alterations

Faculty consider the greatest areas of unmet need in second-line NSCLC, particularly for patients without actionable driver alterations who progress after chemotherapy or chemoimmunotherapy. The panel discusses emerging strategies including PRMT5 inhibition in MTAP-deleted tumors, reviewing the molecular rationale, observed response rates, and questions surrounding resistance and biology in this molecularly selected population. Discussion also addresses antibody-drug conjugates directed at broadly expressed targets, as well as emerging immunotherapy approaches following prior checkpoint inhibition. Faculty share perspectives on novel agents generating interest in this difficult-to-treat setting, including targeted approaches showing promising activity in later lines.