e20127 Background: Tarlatamab, a Delta-like ligand 3 (DLL3)-targeting Bispecific T-cell Engager (BiTE), has shown significant efficacy in heavily pretreated SCLC, leading to its recent approval. However, real-world data on its use, particularly in the rare cohort of patients with extrapulmonary small cell carcinoma (EPSCC), are limited. We report our single-institution experience with tarlatamab in patients with both pulmonary and extrapulmonary SCC. Methods: We conducted a retrospective review of all adult patients with advanced SCLC or EPSCC who received at least one dose of tarlatamab at our center between May 16, 2024, and September 30, 2025. The primary endpoints were Overall Response Rate (ORR), Progression-Free Survival (PFS), and Overall Survival (OS). Safety, including rates of Cytokine Release Syndrome (CRS) and Immune effector Cell-Associated Neurotoxicity Syndrome (ICANS), was a key secondary endpoint. Survival was estimated using the Kaplan-Meier method. Results: A total of 24 patients were included, with a median age of 67 years (range, 55-85). The cohort comprised 19 (79%) patients with SCLC and 5 (21%) with EPSCC (prostate, cervix, GEJ). Patients were heavily pretreated, with a median of 2 prior lines of therapy (range, 1-3). At tarlatamab initiation, 8 (33%) patients had brain metastases and 82% had an ECOG performance status of 0-1. With a median follow-up of 7.5 months, the ORR for the entire cohort was 20.8% (5/24), including 5 partial responses (PR). The median PFS was 4.0 months (95% CI, 1.8 to 5.7). The median OS from the start of tarlatamab was not reached, with a 6-month OS rate of 55%. CRS of any grade occurred in 14 patients (58%), with Grade ≥3 in 2 patients (8%). ICANS of any grade occurred in 7 patients (29%), with Grade ≥3 in 1 patient (4%). Tocilizumab was administered to 12 patients (50%) for management of toxicity. Conclusions: In this real-world cohort, tarlatamab demonstrated meaningful clinical activity and a manageable safety profile. The observed efficacy and toxicity rates are consistent with those reported in the pivotal DeLLphi-301 trial, supporting its use outside of a clinical trial setting. These findings provide valuable insights into the application of tarlatamab across the broader spectrum of DLL3-expressing neuroendocrine malignancies. Baseline characteristics and key toxicities. Characteristic All Patients (N=24) Median age, years (range) 67 (55-85) Female, n (%) 14 (58) Primary Site, n (%) Lung (SCLC) 19 (79) Extrapulmonary (EPSCC) 5 (21) Median prior lines of therapy (range)* 2 (1-3) Brain metastases at baseline, n (%) 8 (33) Cytokine Release Syndrome (Any Grade), n (%) 14 (58) Immune Effector Cell-Associated Neurotoxicity Syndrome (Any Grade), n (%) 7 (29) Tocilizumab Use, n (%) 12 (50) Data for prior lines of therapy were available for 23 patients.
Bangolo et al. (Thu,) studied this question.