Real-world analysis presented at the 2026 SNO/ASCO CNS Metastases conference suggests tarlatamab (DLL3/CD3) shows meaningful intracranial activity in small cell lung cancer patients with brain metastases, including cohorts with active or untreated disease. The retrospective, multi-institution dataset addressed two unanswered operational questions: whether CNS radiation can be delivered safely alongside ongoing T-cell engager therapy and whether continuing tarlatamab beyond isolated CNS progression is feasible. Across 91 patients treated between June 2024 and December 2025, 53 had brain metastases at tarlatamab initiation. Among 36 evaluable patients, the physician-assessed intracranial objective response rate was 38.9%, including complete and partial responses, with disease control at 61.1%. Response rates were reported as 33.3% in the active-untreated group. The reported safety posture did not add new central nervous system toxicity concerns in this real-world context, though the study design inherently limits definitive comparisons. Still, for clinicians, the findings directly tackle a common gap created by pivotal trials that under-enrolled or excluded active brain metastases. The takeaway for the oncology pipeline is that DLL3/CD3 engagement may extend therapeutic reach into a setting where historical options are constrained by blood-brain barrier considerations and prior radiation burden.