Real-World Outcomes of Tarlatamab in Small Cell Lung Cancer, Including Patients With Untreated Brain Metastases

Tarlatamab, a bispecific T-cell engager, has shown promising results in previously treated small cell lung cancer (SCLC) patients in the DeLLphi-300 and DeLLphi-301 trials. However, reports on outcomes in more diverse, real-world patient populations are limited. We retrospectively evaluated safety and efficacy outcomes of all patients who were treated with tarlatamab at the University of Virginia between May and October 2024. Our analysis included 21 patients with SCLC and 1 patient with DLL-3 positive atypical carcinoid. The median age of patients was 66 years (range, 41-80 years), with 59.1% being females. Most patients (85.7%) had extensive stage SCLC at diagnosis. Brain metastases were present in 9 (40.9%) patients and liver metastasis in 14 (63.8%) patients. A total of 18 (81.8%) patients would not have met the DeLLphi-301 inclusion and exclusion criteria. Cytokine release syndrome (CRS) occurred in 16 (72.7%) patients; the median time of onset was 15.8 hours (9.1-18.8) after tarlatamab infusion. Immune effector cell-associated neurotoxicity syndrome (ICANS) occurred in 9 (40.9%) patients, with higher rates and grades observed in patients with untreated brain metastases. The median time of onset was 14.8 h ([IQR] 7.7-22.1) after tarlatamab infusion. After a median follow-up of 6.7 months, the overall response rate (ORR) was 42.9% in SCLC patients. Tarlatamab is a promising treatment option for heavily pretreated small cell lung cancer patients. We observed higher rates of CRS and ICANS during the first treatment cycle suggesting that real-world safety outcomes may differ from clinical trial data.