Real-World Experience of Tarlatamab in Extensive-Stage Small Cell Lung Carcinoma Showed Promising Systemic and Intracranial Efficacy With Higher Neurologic Toxicity.

[PURPOSE] Tarlatamab, a CD3/delta-like ligand 3 bispecific T-cell engager, was approved in 2024 for relapsed extensive-stage small cell lung cancer (ES-SCLC) based on promising clinical trial results. As a T-cell effector therapy, it also has unique side effects, including cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). In this article, we report a real-world series of patients treated with tarlatamab.

[MATERIALS AND METHODS] We retrospectively evaluated safety and efficacy in patients with relapsed ES-SCLC receiving tarlatamab from July 1, 2024, to February 15, 2025, at MD Anderson Cancer Center, including clinical response and toxicity and the radiographic response of brain metastases (BM) per Response Assessment in Neuro-Oncology (RANO)-BM.

[RESULTS] 27 patients were included in our analyses. The median age was 68 (range, 43-83) years, and 15 patients (56%) were women. Before tarlatamab, nine patients (33%) had no BM, and 11 (41%) had active, untreated BM. Of the 22 patients evaluable for response with a median follow-up time of 3 months, four patients (18.2%) had partial response (PR), 71 (31.8%) had stable disease (SD), and 11 (50%) had progressive disease (PD) based on RECIST criteria. Median progression-free survival was 5.9 months (95% CI, 2.6 to not reached). Of the 14 patients with prior BM and serial brain magnetic resonance imaging, based on RANO-BM criteria, two had complete response, one had PR, nine had SD, and only two had PD. Of the four patients without BM, none had new intracranial disease after starting tarlatamab. Of the 27 patients who received cycle 1 day 1 (C1D1) of tarlatamab, 10 (37%) patients developed CRS (1 grade ≥3) and 8 (30%) had ICANS (4 grade ≥3). Of the 25 patients who received C1D8 of tarlatamab, 10 (40%) developed CRS (1 grade ≥3) and 4 (16%) developed ICANS (none grade ≥3).

[CONCLUSION] Tarlatamab demonstrates both intracranial and extracranial efficacy in our real-world patient cohort. Our cohort's toxicity profile showed similar CRS but higher ICANS rates compared with those reported in clinical trials. More studies are needed to determine biomarkers of efficacy and toxicity.