Optimizing tarlatamab therapy for relapsed small cell lung cancer: Biomarker identification and addressing treatment delivery disparity.

e23106 Background: SCLC is a highly aggressive malignancy with limited treatment options and high relapse rates. Tarlatamab, a BiTE targeting DLL3, demonstrates promise with a 40% ORR and a median OS of 12 months. However, challenges persist, including biomarker discovery for response prediction, managing serious toxicities (CRS and ICANS), and addressing barriers to access among underserved populations. Tarlatamab requires 24–48 hours of monitoring after initial doses, posing logistical challenges, particularly in communities with significant social determinants of health (SDOH). Methods: We propose a framework to concurrently advance biomarker discovery and mitigate access disparities at Fox Chase Cancer Center (FCCC) and Temple University Hospital (TUH) in North Philadelphia, where 40% of residents live below the poverty line. After informed consent, a bio-specimen registry will collect pre- and on-treatment blood samples and archival tumor tissues from patients with previously treated extensive-stage SCLC undergoing tarlatamab therapy. Simultaneously, interventions will address logistical barriers to ensure adherence to toxicity monitoring guidelines. Results: Advanced blood- and tissue-based analyses, including flow cytometry and single-cell RNA sequencing, will identify biomarkers predictive of efficacy (ORR, PFS, OS) and toxicity (e.g., TRAEs, CRS, ICANS). Targeted interventions include: 1) Complimentary accommodations within 1 mile of an emergency care facility. 2) Transportation support to ensure timely access to therapy. 3) Outpatient monitoring kits with thermometers, sphygmomanometers, pulse oximeters, and emergency contacts. These kits will include educational materials for side-effect management and caregiver guidance. Patient and caregiver surveys will assess the utility of these interventions and the overall experience. These services are expected to launch in Spring 2025. Conclusions: This framework integrates biomarker discovery with equity-focused interventions to enhance the clinical utility of tarlatamab while addressing disparities in treatment access. By improving outcomes for underserved populations, this approach also offers a model for broader implementation of T-cell engager therapies. This study is supported by the Ride Hard Breathe Easy Foundation, Philadelphia.