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

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Keywords: Bispecific antibody therapy; Real-world; Safety; Small cell lung cancer; Tarlatamab.