Tarlatamab is associated with higher CRS and ICANS rates in real-world settings than observed in trials. Prophylactic tocilizumab may mitigate these toxicities in high-risk patients and should be considered for incorporation into treatment protocols.

Acquired resistance to tarlatamab is associated in some cases with loss of DLL3 expression, but persistence of other targetable neuro-endocrine epitopes; in other patients, DLL3 is retained on CTCs, but accompanied by systemic markers of T cell dysfunction. Quantitation of DLL3-positive CTCs identifies patients likely to benefit from tarlatamab, and longitudinal monitoring may guide therapeutic decision-making at the time of acquired resistance.

P1/2, N=120, Not yet recruiting, National Cancer Institute (NCI)

P1/2, N=138, Recruiting, Molecular Partners AG | Not yet recruiting --> Recruiting | Trial completion date: Sep 2030 --> Sep 2032

P3, N=420, Recruiting, Suzhou Zelgen Biopharmaceuticals Co.,Ltd | Not yet recruiting --> Recruiting

P1/2, N=350, Recruiting, Suzhou Zelgen Biopharmaceuticals Co.,Ltd | Not yet recruiting --> Recruiting

P1/2, N=54, Recruiting, Suzhou Zelgen Biopharmaceuticals Co.,Ltd | Trial completion date: Oct 2025 --> Oct 2026 | Trial primary completion date: Sep 2025 --> Sep 2026

We applied CyTOF and a 20-marker antibody panel to detect and phenotype CTCs directly in liquid biopsies of 51 SCLC patients (treatment-naïve, chemotherapy and immunotherapy-treated, and tarlatamab-treated), of which a subset were longitudinally tracked...Our study demonstrates the utility of CyTOF for high-resolution CTC profiling, offering dynamic insights into CTC heterogeneity, treatment response, and resistance mechanisms. CTCs can be detected, subtyped and phenotyped in SCLC liquid biopsies using CyTOFCTC subtypes and EMT states are differentially associated with treatment modalityCTC DLL3 levels and epithelial features increase following anti-DLL3 BiTE therapyCyTOF CTC subtyping can predict disease aggressivenessLongitudinal tracking reveals CTC plasticity and therapy response correlations.

P2, N=222, Active, not recruiting, Amgen | Trial completion date: Apr 2027 --> Dec 2027 | Trial primary completion date: Apr 2026 --> Dec 2026

P1, N=46, Active, not recruiting, Boehringer Ingelheim | Trial primary completion date: Dec 2025 --> Sep 2026

Most data come from SCLC; in the other two diseases, tarlatamab is in early clinical development. Tarlatamab is an effective therapy mainly in relapsed/progressed SCLC, and its assessment in limited SCLC alone or combined with other therapies is supported by the existing data.

P1/2, N=138, Not yet recruiting, Molecular Partners AG