Dr Cooper on Biomarker Selection for DLL3-Targeted Therapies in ES-SCLC

“We know that some patients have a much better response to tarlatamab than others, and we’re starting to try to understand [whether] there [are] underlying predictive biologic biomarkers that can help us understand who those patients are.”

Alissa Cooper, MD, instructor in medicine at Harvard Medical School and physician at Dana-Farber Cancer Institute, discussed evolving strategies for biomarker-driven patient selection with tarlatamab-dlle (Imdelltra) in small cell lung cancer (SCLC), a topic covered in the Bridging the Gaps in Lung Cancer meeting.

Cooper noted that the field is evolving quickly on this question. Currently, all patients with SCLC are considered eligible for tarlatamab therapy, she explained. However, she acknowledged that some patients respond considerably better than others, prompting efforts to identify underlying predictive biomarkers that could help distinguish these populations.

Cooper highlighted developing evidence suggesting that DLL3 expression may serve as a biomarker associated with improved outcomes on tarlatamab, though she cautioned that this work has so far been limited to small patient cohorts and is not yet ready for routine clinical application. She also pointed to transcriptional phenotypes, or subtypes, of SCLC as another area worth considering, noting that neuroendocrine-high subtypes have shown better outcomes with DLL3-targeted T-cell engagers like tarlatamab.

Cooper identified the major outstanding questions in terms of how such biomarker testing should be operationalized: whether it should occur at initial diagnosis, and whether it should rely on immunohistochemistry or RNA-based methods. She also raised the practical challenge of turnaround time, noting that patients with SCLC are often quite ill and need to start therapy quickly, raising the question of whether they can wait for biomarker results. Ultimately, she concluded that the field needs to determine how to operationalize any validated biomarkers rapidly enough to meet these patients’ urgent treatment needs.