Exploring Investigational Approaches Including Cellular Therapy

The expanding small cell lung cancer (SCLC) therapeutic landscape includes promising investigational approaches such as DLL3-directed CAR T-cell therapy, which offers the potential for single-dose treatment with durable responses. Dr Leal describes an autologous DLL3-targeted CAR T incorporating dominant-negative TGF-ß to overcome tumor-mediated immunosuppression, showing preliminary safety signals with no dose-limiting toxicities across initial dose levels. The 20% response rate and 70% disease control rate demonstrate encouraging activity, with apparent dose-related efficacy suggesting potential for optimization as dose escalation continues.

Radioligand therapy targeting DLL3 represents another innovative approach under development, offering the potential for targeted radiation delivery to SCLC cells expressing this target. The panel expresses particular enthusiasm for CAR T-cell therapy’s single-dose convenience compared to ongoing treatments, though noting the requirement for lymphodepletion and potential need for bridging therapy during manufacturing. These cellular therapies may offer advantages for patients who cannot tolerate prolonged treatment courses or frequent clinic visits required by other novel approaches.

The discussion highlights the rapid evolution of SCLC treatment options, with multiple novel mechanisms of action entering clinical development simultaneously. The experts anticipate that understanding optimal sequencing of these diverse approaches will become increasingly important as more therapies receive regulatory approval. The challenge will be determining how to integrate single-dose therapies like CAR T with ongoing treatments like T-cell engagers and ADCs, requiring careful consideration of patient factors, disease characteristics, and treatment goals to optimize outcomes in this evolving therapeutic landscape.