MMDA-06 INTRACRANIAL EFFICACY AND TREATMENT BEYOND CNS PROGRESSION WITH TARLATAMAB IN SMALL CELL LUNG CANCER: A MULTI-INSTITUTIONAL REAL-WORLD ANALYSIS

Abstract

Brain metastases (BMs) affect approximately half of patients with relapsed SCLC, yet DeLLphi-304 excluded patients with active or symptomatic BMs. The safety and efficacy of integrating CNS-directed radiation with tarlatamab remain undefined. We conducted a multi-institutional retrospective study of patients with SCLC treated with tarlatamab (June 2024–December 2025). BM status was classified by imaging within 8 weeks of C1D1. Patients with BMs receiving prior local therapy (SRS/WBRT) were classified as treated; those without prior treatment were classified as active. Intracranial efficacy, ICANS rates by radiation timing, and treatment beyond CNS progression (TBP) were evaluated. Physician-assessed intracranial responses were collected. Of 79 patients, 48 (61%) had BMs at tarlatamab initiation: 14 active and 32 treated. Prior CNS radiation included SRS (n = 20) and WBRT (n = 12). Among 30 evaluable patients, intracranial ORR was 37% (3 CRs, 8 PRs) and DCR was 63%. Active BM patients achieved intracranial ORR of 40% (4/10) and treated BM patients 35% (7/20). Patients receiving CNS radiation ≤14 days before tarlatamab had numerically higher ICANS rates (47% vs. 23%; all grade ≤2). Eight patients received CNS radiation during tarlatamab with no associated ICANS. Overall CRS occurred in 57% (grade 3: 5%) and ICANS in 28% (grade 3: 3%). Nine patients (60% with CNS progression) continued tarlatamab beyond CNS progression for a median of 99 additional days; 8/9 received local CNS therapy and 6/9 had oligometastatic disease (≤3 lesions). One patient with leptomeningeal disease received spinal radiation and continued tarlatamab for 41 days. Tarlatamab demonstrates meaningful intracranial activity in real-world SCLC patients with BMs, including those with active disease. Concurrent CNS radiation during tarlatamab appears safe, though recent pre-tarlatamab CNS radiation (≤14 days) may increase ICANS risk. Notably, treatment beyond oligometastatic CNS progression with concurrent SRS is feasible and may meaningfully extend tarlatamab duration.