Dr Choudhury on Understanding Mechanisms of Resistance to DLL3-Directed BiTEs in SCLC

“Tissue-based studies would be ideal to really help us understand what’s the optimal sequence, and how we can potentially consider future strategies such as rechallenge.”

Noura Choudhury, MD, an assistant professor of medicine at the University of Chicago Medicine, discussed how resistance mechanisms to tarlatamab-dlle (Imdelltra) could inform sequencing decisions in small cell lung cancer (SCLC), a topic covered in the Bridging the Gaps in Lung Cancer meeting.

Choudhury explained that understanding the mechanism behind resistance matters significantly for treatment sequencing. If tumors lose DLL3 expression at the time of progression it likely wouldn’t make sense to follow tarlatamab with a DLL3-targeted antibody-drug conjugate (ADC), she noted. Alternatively, if DLL3 expression is retained but T cells lose their functional ability to kill tumor cells, that scenario could represent an ideal opportunity to pivot to a different treatment class, such as an ADC, she added.

Choudhury noted that current understanding of resistance mechanisms is limited, based largely on circulating tumor cell data, underscoring the need for further research. She emphasized that tissue-based studies would be especially valuable in clarifying the optimal treatment sequence and in informing future strategies, including the potential for treatment rechallenge.