Performance status and tarlatamab outcomes in a large, multi-institution real-world database of 2L+ ES-SCLC.

e20120 Background: Tarlatamab is a novel bispecific T-cell engager approved for 2L+ extensive stage small cell lung cancer (ES-SCLC). Previously published real-world single-institution studies have been small (n=22) and (n=39); in both, tarlatamab resulted in inferior survival with higher rates of CRS and ICANS than observed in the DeLLphi-304 trial. To better understand real world outcomes with tarlatamab, we examined a much larger, multi-institutional dataset. Methods: Utilizing the US-based, electronic health record-derived, deidentified Flatiron Health Research Database, patients with ES-SCLC treated with tarlatamab between 3/2024 and 09/2025 were selected. Baseline characteristics, treatment history, and clinical outcomes were abstracted. Chi-square and t-tests were used for used for univariate analysis. Median time to treatment discontinuation (mTTD), real-world progression-free survival (mPFS) and overall survival (mOS) from start of tarlatamab were estimated via Kaplan Meier curves. Effects of patient baseline characteristics were estimated via log-rank analysis and Cox regression. Results: Of 204 patients included, 90 (44%) were female. Median age at start of therapy was 66.4 years. 158 (77%) were white, 24 (12%) Black. At initiation of tarlatamab, 62 (30%) patients were ECOG PS 0, 86 (42%) were 1, 48 (24%) were 2+. 75 (37%) received tarlatamab in 2L, 64 (32%) in 3L, and 65 (31%) in 4L+. 109 (53%) patients previously received lurbinectedin; only 15 (7%) received subsequent therapy. mPFS from start of tarlatamab was 3.8 months(m), mTTD was 2.3m, and mOS was 11.2m. Patients treated in 2L had mPFS of 5.3m and mOS of 12.2m, compared to 3.4m (p=0.36) and 8.1m (p=0.81) in 3L+. Patient sex, race (Black vs White) and age (<65 vs ≥65yo) were not associated with TTD, PFS, or OS (Table 1). ECOG ≥2 PS was associated with shorter mPFS vs ECOG 0-1 (2.1 vs 4.5; p=0.004), mTTD (1.6 vs 2.8; p=0.001) and mOS (3.2 vs 13.4; p<0.001) vs ECOG 0-1. Conclusions: In the largest retrospective analysis to date, mTTD, mPFS, and mOS with tarlatamab in pts with intact PS (0-1) appear similar to outcomes reported in DeLLphi-304. However, ECOG PS ≥2 was associated with significantly shorter TTD, PFS, and OS, which may account for inferior real-world outcomes compared to the trial. Line of therapy in our cohort was not associated with outcomes, nor was race, sex or age. Baseline characteristics and survival. Table 1 mPFS p-value mTTD p-value mOS p-value All 3.8 2.3 11.2 2L 5.3 P=0.44 2.8 P=0.33 12.2 P=0.92 3L+ 3.4 2.0 8.1 Female 3.8 P=0.96 2.4 P=0.61 13.4 P=0.88 Male 3.9 2.3 11.2 Black 3.5 P=0.66 2.4 P=0.45 11.2 P=0.75 White 4.7 2.2 13.8 Age <65 3.9 P=0.74 2.7 P=0.90 12.8 P=0.66 Age≥65 3.6 2.2 11.0 ECOG 0-1 4.5 P=0.004 2.8 P=0.001 13.4 P=0.002 ECOG 2+ 2.1 1.6