New real-world data suggest tarlatamab may produce clinically meaningful intracranial responses in small cell lung cancer patients with brain metastases, including groups that were underrepresented in pivotal trials. Findings presented at the 2026 SNO/ASCO CNS Metastases conference analyzed patients treated with tarlatamab between June 2024 and December 2025, including individuals with previously treated and untreated active brain disease. Across evaluable patients, the physician-assessed intracranial objective response rate was 38.9%, with a disease control rate of 61.1%. In the subset classified as active at baseline, intracranial ORR was 33.3%. The results address two practical questions for CNS progression management—whether CNS radiation can be given alongside a T-cell engager and whether continuing tarlatamab through isolated intracranial progression is feasible—using a larger, more heterogeneous cohort than earlier studies.