Real-world efficacy and safety of tarlatamab in small cell lung cancer and extrapulmonary neuroendocrine carcinoma.

e20166 Background: Patients with extensive-stage small cell lung cancer (ES-SCLC) and extrapulmonary neuroendocrine carcinoma (EP-NEC) have limited treatment options after progression on platinum-based chemotherapy and immunotherapy. Tarlatamab, a DLL3xCD3 bispecific T-cell engager, is approved for previously treated ES-SCLC. While clinical trials have characterized its efficacy and toxicity, real-world data describing the timing and severity of cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS) remain limited. Methods: We conducted a retrospective chart review of adults with ES-SCLC or EP-NEC who received ≥1 dose of tarlatamab between October 2024 and October 2025. Primary endpoints were the incidence and timing of CRS and ICANS. Progression-free survival (PFS) was estimated using Kaplan-Meier methods. Results: Of 26 patients screened, 22 met inclusion criteria. Median age was 64 years (range, 50–84), and 12 patients (55%) were female. Among the cohort, 18 patients (82%) were White, 4 patients (18%) were Black, and Hispanic ethnicity was reported in 7 patients (32%). Brain and liver metastases were present in 7 (32%) and 10 (46%) patients, respectively; one patient had EP-NEC. CRS occurred in 9 patients (41%), including grade 1 in 3 (14%), grade 2 in 5 (23%), and grade 4 in 1 (5%). ICANS occurred in 8 patients (36%), including grade 1 in 2 (9%), grade 2 in 6 (27%) with no grade ≥3 events. Median time to onset was 16.4 hours for CRS and 15.8 hours for ICANS, occurring predominantly during cycle 1. CRS and ICANS were managed with standard interventions, including tocilizumab and/or corticosteroids. One patient (5%) experienced grade 4 CRS and grade 2 ICANS, requiring vasopressor support and ICU admission. Median PFS was 4.1 months, with 11 patients (50%) remaining on therapy at the time of analysis (PFS to be updated at time of ASCO 2026 meeting). Conclusions: In this real-world cohort, tarlatamab was associated with early-onset CRS and ICANS, which were predominantly low-grade, though rare high-grade events occurred. Despite ICANS rates higher than those reported in clinical trials, toxicities were generally manageable with standard supportive measures. These findings support the feasibility of tarlatamab in diverse clinical populations when supported by appropriate clinical and oncology pharmacy-driven interventions.