A retrospective multi-institution analysis presented at the 2026 SNO/ASCO CNS Metastases conference reports intracranial responses with tarlatamab in small cell lung cancer patients with brain metastases, including some with active, untreated disease. Investigators assessed whether CNS radiation can be safely paired with the T-cell engager and whether continuing tarlatamab after isolated CNS progression is feasible. Across 91 patients treated between June 2024 and December 2025, the physician-assessed intracranial objective response rate was 38.9%, with 3 complete responses and 11 partial responses. In the subset classified as active at baseline (n=20), ORR was 33.3% in 36 evaluable patients, with a disease control rate of 61.1% overall. The findings address a common gap in CNS-active T-cell engager evidence because pivotal trials often under-enroll or exclude active brain metastases. While retrospective design limits causal inference, the data provide a practical benchmark for clinicians managing CNS involvement during tarlatamab treatment.