Real-world outcomes of tarlatamab across small cell carcinoma subtypes, including transformed and non-lung primary.

e23350 Background: Tarlatamab, a bispecific antibody targeting delta-like ligand-3 and CD3, has been approved for small cell lung cancer (SCLC) following progression on chemo-immunotherapy. However, the benefit of Tarlatamab in patients with transformed small cell cancer or primary small cell carcinoma of a non-lung site remains unclear. We report real-world outcomes of Tarlatamab in patients with small cell carcinoma, including transformed disease and non-lung primary. Methods: We performed a retrospective review of patients who received at least one dose of Tarlatamab at our institution between June 2024 and January 2026. Patients were identified as SCLC or transformed and non-lung primary (T/NL). Progression-free survival (PFS) was defined as time from first dose until progression or death. Overall survival (OS) was defined as time from first dose until death. Since some patients with disease progression in the central nervous system (CNS) alone were treated with radiation and continued Tarlatamab, we calculated a PFS excluding CNS progression. Patients were censored at the date of last known with no progression or alive. Duration of Response (DoR) was defined as time from first response until time of progression in patients with confirmed response. Results: Among 37 patients that received Tarlatamab, median age was 69, and 19 were female (51.4%). Median prior therapies was 2. Thirty patients had SCLC, and 7 had T/NL. Thirty-three patients were evaluated for response as 4 enrolled on hospice before assessment. Seventeen patients (51.5%) had a response, including 4 of the 7 (57.1%) T/NL. For all patients, median OS (mOS) was 7.3 months, median PFS (mPFS) was 2.3 months, and mPFS excluding CNS progression was 2.3 months. Median DoR (mDoR) was 2.7 months, and mDoR excluding CNS progression was 4.7 months. Estimated 12-month survival was 28% (11 – 49%). In T/NL patients, mOS was not reached at a median follow up of 3.9 months. Median PFS was 2.9 months, and mPFS excluding CNS was 12.3 months. Median DoR was 4.2 months while mDoR excluding CNS was 8.4 months. Estimated 12-month survival of the T/NL cohort was 63% (14 – 89%). Cytokine release syndrome (CRS) was seen in 54.1% (20/37) and 18.2% (6/33) of patients on day 1 and day 8, respectively. Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) was seen in 5.4% (2/37) and 3.0% (1/33) of patients on day 1 and day 8, respectively. All CRS and ICANS events were grade 1 or 2. Conclusions: This real-world analysis of Tarlatamab demonstrated slightly worse clinical outcomes with respect to PFS and OS although similar tolerability compared to the clinical trial. Notably, transformed and non-lung primary small cell carcinoma patients showed promising outcomes with Tarlatamab. This study was limited by the small sample size but highlights the importance of further studies of Tarlatamab in this unique patient population.