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

e20127 Background: Small cell lung cancer (SCLC) remains the most aggressive lung cancer with poor prognosis. Tarlatamab (T), a bi-specific T-cell engager, is approved for use in extensive stage SCLC after progression on a platinum-based chemotherapy based on the DeLLphi-301 trial. Due to the restrictive inclusion criteria of this trial, significant gaps remain in understanding treatment outcomes for many patients (pts). Methods: This is a single-center, IRB-approved, retrospective study in pts who were treated with T from 05/2024 to 12/2024 for SCLC (cohort 1) or extrapulmonary small cell carcinoma (cohort 2). Pts were eligible if they received at least 1 dose of T. The primary objective was to evaluate the safety of T and secondary objectives include response rate (RR), progression-free survival (PFS) and overall survival (OS). Results: A total of 21 pts were included in cohort 1 and 3 pts were included in cohort 2. Baseline characteristics can be found in the Table. In cohort 1,13 pts (61.9%) developed cytokine release syndrome (CRS) (Grade ≥ 3: 2 pts,15.3%). 10 pts (47.6%) developed immune effector cell associated neurotoxicity syndrome (ICANS) (Grade ≥ 3: 3 pts,14.2%). In cohort 2, any grade CRS occurred in 2 pts (66.7%) and grade 1 ICANS occurred in 1 pt (33.3%). All CRS and ICANS events occurred after cycle 1 day 1(C1D1), except for 1 pt who experienced transient grade 1 CRS on cycle 1 day 8. 17 pts were evaluated for response in cohort 1 (PR=35.2%, SD=17.6%). Notably, the RR in pts with T use in the 2nd line and with liver metastasis (mets) was 40% and 38.5%, respectively. Median PFS was 2.2 months and median OS was 4.1 months. 1 pt noticed a CR in the CNS without any radiation. Conclusions: Our study showed the safety and ORR of T are consistent with findings from the DeLLphi-301 trial. However, median PFS and OS were notably shorter, likely due to the small sample size and the inclusion of pts with poor prognostic factors like oxygen use, poor ECOG status, and untreated CNS mets. The higher incidence of CRS and ICANS following C1D1 highlights the need for vigilant monitoring during initial cycles. Future studies with larger pt population and longer follow-up are warranted to evaluate T in the real-world settings. Cohort 1 (21 pts) Cohort 2 (3 pts) Median age, yr 67 74 Sex, no. (%) M/F 11(52.3)/10(47.6) 2(66.7)/1(33.3) Ethnicity, no. (%) W/AA/A 19(90.4)/1(4.8)/1(4.8) 2(66.7)/1(33.3)/0(0) ECOG, no. (%) 0-1/2+ 16(76.1)/5(23.8) 2(66.7)/1(33.3) Brain mets, no. (%) 14(66.6) 2(66.7) Liver mets, no. (%) 16(76.1) 2(66.7) Baseline Oxygen Use, no. (%) 5(23.8) 0(0) Metastatic sites <5/>5 11(52.4)/10(47.6) 2(66.7)/1(33.3) CR/PR/SD/PD, no. (%) 0(0)/6(35.2)/3(17.6)/8(47) Unevaluable CRS C1D1 Any Grade/3+ 13(61.9)/2(9.5) 2(66.7)/0(0) ICANS C1D1 Any Grade/3+ 10(47.6)/3(14.3) 1(33.3)/0(0) Best Response by Baseline characteristic, no. (%)Liver mets2 nd line tarlatamabPlatinum resistant 5/13 (38.5)2/5 (40)1/8 (12.5)