Predictive markers of response and toxicity to tarlatamab in patients with extensive stage small cell lung cancer (ES-SCLC): A multi-institutional real-world analysis.

Abstract

8097 Background: Tarlatamab (tarla) is a novel immunotherapeutic agent for the treatment of relapsed ES-SCLC associated with favorable response and survival outcomes. While tarla’s unique side effect profile of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) is well described, factors influencing response or toxicity have yet to be fully established. Methods: We performed a retrospective, multivariate analysis of patients with ES-SCLC receiving tarla at three NCI-designated comprehensive cancer centers from 7/2024-10/2025. CRS and ICANS were reported using ASTCT consensus guidelines. Dysgeusia was graded using CTCAE v5.0. Overall response rate (ORR) was determined using clinical interpretation of radiographic assessments from patients with available post-treatment imaging. Time to event analyses were performed. Cox Proportional Hazards regression analyses assessed the association between patient characteristics and PFS and OS outcomes. Logistic and ordinal regression analyses evaluated the predictive value of variables contributing to the presence and severity, respectively, of CRS and ICANS. Results: 115 patients received at least 1 dose of tarla, with median age of 67 years, 55% female and ECOG PS ranging from 0-3 (median of 1). Rates of observed CRS, ICANS, and dysgeusia were 46%, 28%, and 47%, respectively. ORR was 44% and 6-month PFS/OS rates were 30.4% (95% CI: 22.5-41.1%)/54.9% (95% CI: 45.4-66.4%). Excluding patients on tarla <30 days, presence of dysgeusia was associated with a lower rate of progression (HR 0.44, p = 0.00691) and death (HR 0.34, p = 0.0145). Neither CRS nor ICANS were associated with treatment response. Both sum of liver metastasis diameter >10 cm (OR 4.4, p = 0.02) and elevated baseline LDH (p = 0.01) were significantly associated with increased likelihood of CRS, while female sex was a protective factor (OR 0.33, p = 0.01). Increased ECOG PS (OR 2.3, p = 0.02), sum of brain metastasis diameter >2 cm (OR 3.6, p = 0.02), development of CRS (OR 2.8, p = 0.04), elevated baseline LDH (p = 0.04) and elevated baseline ferritin (p =0.004) were all associated with increased risk of developing ICANS. Conclusions: In our multicenter cohort of patients with ES-SCLC, tarlatamab continued to demonstrate anticancer activity with similar ORR and 6 month PFS compared to existing DeLLphi-304 data. Importantly, the presence of dysgeusia was found to be a marker of treatment response associated with improved PFS and OS. CRS and ICANS incidence was associated with several baseline patient and disease characteristics. Collectively, these preliminary results identify several predictive biomarkers of toxicity that can be utilized in clinical practice, though validated models are needed to better stratify low and high-risk populations.