Real-world efficacy and safety of tarlatamab in patients with relapsed extensive-stage small cell lung cancer.

8088 Background: Tarlatamab, a bispecific T cell engager targeting Delta-Like ligand 3, received FDA approval in May 2024 for patients with relapsed extensive-stage small cell lung cancer (SCLC). While the clinical trials leading to its approval demonstrated impressive objective response, it has unique toxicities including cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Here, we report a real-world case series of safety and efficacy data for patients treated with standard of care tarlatamab at MD Anderson Cancer Center. Methods: We queried the MD Anderson Lung Cancer GEMINI database for patients treated with tarlatamab and retrospectively collected demographic, clinical, and outcome data. From 7/1/2024-1/15/2025, a total of 39 patients received tarlatamab. 8 patients were excluded from analysis either due to diagnosis of extrapulmonary small cell cancer or rapid clinical deterioration due to disease progression around the time of the first tarlatamab infusion. The final cohort consisted of 31 patients. Results: The average age of our cohort was 66 years, 36% of patients were of non-white race, and their median lines of prior treatment was 2. 4 patients had transformed SCLC from classical EGFR-mutant lung adenocarcinoma (EGFR transformed), and 12 patients had untreated brain metastases (BM) prior to tarlatamab initiation. Safety data is summarized in the Table. At the cutoff, 17 patients had their first repeat systemic imaging: 59% had tumor shrinkage, 12% had stable or mixed tumor response, and 29% experienced tumor growth. Of the 3 EGFR transformed cases that had a repeat imaging on treatment, 2 had tumor growth. 18 patients underwent a repeat brain magnetic resonance imaging (MRI) after tarlatamab treatment. Out of 11 patients with untreated BM, 82% (9) had intracranial tumor shrinkage or stability, and 2 patients had mixed response, one of which was an EGFR transformed case. Of the 7 patients who either had no prior BM or had BM treated with radiation, only 1 had developed new BM (EGFR transformed). Conclusions: Preliminary data from this cohort show efficacy comparable to that observed in clinical trials. Notably, we report impressive intracranial response in patients with untreated BM. The toxicity profile reveals similar CRS but higher ICANS rates compared to those reported in the clinical trials. Additional data collection and analyses are ongoing at this time. Safety data from C1D1 and C1D8 of Tarlatamab. Adverse Event Hospitalization for C1D1 of Tarlatamab 1 mg IV (N=31) Hospitalization for C1D8 of Tarlatamab 10 mg IV (N=28) Cytokine-release syndrome – no. (%) Overall 12 (39) 11 (39) Grade 3 or more 1 (3) 1 (4) Tocilizumab Administration 8 (26) 4 (14) ICANS – no. (%) Overall 8 (26) 4 (14) Grade 3 or more 3 (10) 0 (0) Adverse event leading to ICU stay – no. (%) 4 (13) 1 (4)