WCLC 2025 - Posters & ePosters-PT2.13.04 Real-World Multi-Institution Analysis of Patients With Small Cell Lung Cancer Treated With Tarlatamab

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This multi-institution retrospective study evaluated real-world outcomes of 102 patients with small cell lung cancer (SCLC) treated with tarlatamab, a DLL3/CD3 bispecific T-cell engager approved as standard second-line therapy. Data were collected between May 2024 and June 2025 from three major U.S. academic centers. The cohort included a high proportion (50%) of patients who would have been ineligible for the registrational clinical trials based on factors like ECOG performance status >1, history of pneumonitis or interstitial lung disease, untreated brain metastases, organ dysfunction, oxygen requirement, pleural effusion, recent stroke, or reduced ejection fraction.<br /><br />Key findings showed that trial-eligible patients experienced longer median treatment durations (4.77 months vs. 2.13 months) and better clinical responses, with ineligible patients more frequently showing disease progression (PD) rather than benefit. Remarkably, cytokine release syndrome (CRS) incidence and severity did not differ significantly between eligible and ineligible groups, occurring in approximately 55% of patients after the first dose, mostly grade 1–2. However, immune effector cell-associated neurotoxicity syndrome (ICANS) was significantly more common in trial-ineligible patients but was not correlated with baseline CNS metastases or prior CNS radiation. Risk modeling suggested female sex, liver metastases, and three or more metastatic sites as potential predictors for CRS development.<br /><br />Demographically, the median age was mid-60s, with roughly equal sex distribution and predominantly White race. Most patients had extensive-stage disease and had received one or more prior therapies. The findings highlight that half of tarlatamab-treated patients in practice would not meet trial enrollment criteria and tend to have shorter treatment exposure and poorer outcomes. The study underscores the need for further research into clinical and biological biomarkers to predict safety and efficacy of DLL3-targeted bispecific T-cell engagers, especially to optimize patient selection and manage side effects like ICANS and CRS in broader patient populations outside clinical trials.

Asset Subtitle

Alissa Cooper

Meta Tag

Speaker Alissa Cooper

Topic Small Cell Lung Cancer and Neuroendocrine Tumors

Keywords

small cell lung cancer

tarlatamab

DLL3/CD3 bispecific T-cell engager

real-world outcomes

clinical trial eligibility

cytokine release syndrome

immune effector cell-associated neurotoxicity syndrome

treatment duration

predictors of CRS

biomarkers for safety and efficacy