Brief Report: Multi-Institution Real-World Analysis Evaluating Safety, Efficacy, and ctDNA Dynamics After Tarlatamab in Patients With Previously Treated SCLC and LCNEC

Tarlatamab, a bispecific T-cell engager targeting delta-like ligand 3 and CD3 on T cells, has generated impressive treatment response rates in relapsed extensive-stage SCLC and large cell neuroendocrine carcinoma. We performed a retrospective, multi-institutional analysis of 48 patients who received tarlatamab as standard of care to assess how safety and efficacy outcomes translate into real-world practice. Rates of cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome were 54% and 33%, respectively, with most being grades 1 to 2 in severity (100% and 87.5%). Of the 30 patients included in our efficacy analysis, the best overall response rate was 67% and disease control rate was 73%. With median follow-up of 5.7 months, median progression-free survival was 4.9 months (95% confidence interval: 4-not reached) and median overall survival was not reached (95% confidence interval: 4.8-not reached). Nine patients underwent molecular response assessment, with circulating tumor DNA trends corresponding with radiographic response. In this multicenter cohort study, tarlatamab continued to demonstrate encouraging response rates and progression-free survival; however, differences were observed in rates and timing of key treatment-associated toxicities compared with previous trial data.