DLL3 positive

Her tumor strongly expressed DLL3 protein and had clinical response to tarlatamab therapy. This case indicates that this novel therapy may be an efficacious option in other pulmonary neuroendocrine cancers.

Our results suggest that ICI+chemo and DLL3-targeting agents are worth further exploration in EGFR+ NSCLC undergoing SCT.

Both IHC and mRNA ISH showed significant correlation in tumors and lymph node metastasis. An observed trend suggested improved survival in patients with no DLL3 expression.

High-grade and low-grade MTC have different expression profiles. DLL3 should be explored as a predictor of aggressive disease and poor outcome in MTC.

No abstract available

Integrating CellSearch, DEPArray, and low-pass sequencing provides a minimally-invasive approach to compare genomic characteristics in DLL3-positive and negative CTCs from SCLC patients. Extension of this approach to a larger patient cohort and employing machine learning algorithms will facilitate identification of patterns within diverse CNA profiles, improving patient stratification and predicting treatment responses for personalized therapeutic strategies in SCLC.

Key exclusion criteria: extracranial metastatic or leptomeningeal disease; previous treatment with DLL3-targeting therapies; prior treatment with bevacizumab/other anti-VEGF/anti-angiogenic treatment ≤6 months prior to first administration of BI 764532; persistent toxicity from previous treatments that has not resolved to ≤CTCAE Grade 1; diagnosis of immunodeficiency, or intake of immunosuppressive therapy ≤7 days prior to first administration of BI 764532. Primary endpoints: dose-limiting toxicities (DLTs) during the maximum tolerated dose evaluation period (escalation phase); DLTs during the entire treatment period (expansion phase). Other objectives include pharmacokinetics, pharmacodynamics, preliminary efficacy and evaluation of DLL3 as a potential biomarker.

Promising efficacy was observed in pts with epNEC. The study is ongoing.

In the dose escalation part, the primary endpoint is dose-limiting toxicity (DLT) occurrence in the MTD evaluation period; secondary endpoints include DLT occurrence in the on-treatment period, objective response and pharmacokinetics. Enrolment is ongoing.

BI 764532 showed clinically manageable tolerability and MTD has not been reached at the doses administered to date. Promising efficacy has been observed, not only in SCLC but also in difficult to treat entities such as NEC and LCNEC. The study is ongoing; updated data will be presented.

We therefore developed a DLL3/CD3/CD137 trispecific T cell engager composed of two CD3/CD137 dual specific Fabs and one extra DLL3 Fab (DLL3 trispecific, RG6524). We initially investigated the CD3 and CD137 signal transduction in Jurkat cells harboring NFAT or NF-κB reporter cocultured with DLL3 positive cells...Likewise, tocilizumab treatment did not reduce the efficacy, suggesting that CRS mitigation did not abrogate the therapeutic benefit.We finally assessed the tolerability in non-human primates. Our data showed that DLL3 trispecific has potent activity and is well suited for clinical application in SCLC. These findings provide a rationale for the clinical testing of DLL3 trispecific.

The current review elucidates the characteristics and related regulating pathways of lung CSCs from essential to preclinical research. We retrospectively introduce an update on the clinical development of therapeutics targeting CSC-associated developmental signaling pathways and discuss the opportunities to target CSC-immune interactions in lung cancer.