Key Efficacy and Safety Insights From Emerging Therapies in SCLC

Antibody-drug conjugates (ADCs) targeting B7-H3, including sacituzumab and datopotamab deruxtecan, demonstrate impressive response rates of approximately 60% in small cell lung cancer (SCLC), representing efficacy levels not previously achieved with traditional cytotoxic therapies. Dr Sands notes that these response rates exceed those seen with lurbinectedin, which achieved FDA approval with a 35% response rate, suggesting significant therapeutic advancement. The panel discusses ongoing studies combining T-cell engagers with B7-H3 ADCs, expressing optimism about potential synergy that could improve durability of responses beyond what either therapy achieves alone.

The development pipeline includes multiple ADC targets, with SLFN11-directed ADCs and DLL3-targeted ADCs showing promise in early studies. Dr Cooper highlights that some ADCs retain efficacy even after progression on DLL3-targeted T-cell engagers, suggesting that different mechanisms of action may overcome resistance even when targeting the same antigen. The panel also discusses tri-specific T-cell engagers and CAR T-cell therapies targeting DLL3, with early data suggesting potential for durable responses, though larger studies are needed to establish their role in SCLC treatment algorithms.

Patient selection considerations for these emerging therapies remain under investigation, with the panel prioritizing T-cell engagers for their demonstrated potential for durable responses. While ADCs offer convenience as outpatient therapies without the monitoring requirements of T-cell engagers, the experts note that ongoing toxicity profiles may offset the initial convenience advantage. The decision between therapies may ultimately depend on patient preferences regarding hospitalization requirements, tumor burden considerations, and contraindications to specific treatment modalities, though optimal sequencing strategies remain to be determined through clinical experience and ongoing research.