Dr Avanish Mishra speaks to ecancer about a novel biomarker approach to predict response to tarlatamab, a DLL3-targeted bispecific T-cell engager, in patients with small cell lung cancer.

Using single-cell analysis of circulating tumour cells collected prior to treatment, researchers identified distinct patient groups based on DLL3 expression levels.

Patients with high DLL3 expression in circulating tumour cells consistently experienced clinical benefit, while those with low expression were more likely to have disease progression.

This approach demonstrated high sensitivity and specificity, offering a promising strategy for patient stratification.

The study also provided insights into mechanisms of resistance, including loss of DLL3 expression or persistent expression accompanied by T-cell dysfunction. Importantly, alternative tumour markers remained detectable, suggesting potential future therapeutic targets.

Dr Mishra says that these findings highlight the potential of a non-invasive, real-time blood-based biomarker to guide treatment decisions and improve outcomes for patients receiving tarlatamab, with broader implications for other neuroendocrine cancers.