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    BIOMARKER:

    DLL3 expression

    i
    Other names: DLL3, Delta Like Canonical Notch Ligand 3, Drosophila Delta Homolog 3, Delta-Like Protein 3, Delta3, Delta (Drosophila)-Like 3, Delta-Like 3 (Drosophila), Delta-Like 3, SCDO1
    Entrez ID:
    10683
    Related biomarkers:
    Expression
    2d
    DAREON ® -Lung-1: A Study in People With Advanced Small Cell Lung Cancer to Compare Obrixtamig Plus Atezolizumab, Carboplatin, and Etoposide Treatment With Standard Chemotherapy (clinicaltrials.gov)
    P3, N=670, Recruiting, Boehringer Ingelheim | Not yet recruiting --> Recruiting
    Enrollment open
    |
    DLL3 (Delta Like Canonical Notch Ligand 3)
    |
    DLL3 expression
    |
    VENTANA DLL3 (SP347) Assay
    |
    Tecentriq (atezolizumab) • carboplatin • etoposide IV • obrixtamig (BI 764532)
    8d
    A Study of 177Lu-DTPA-SC16.56 in People With Neuroendocrine Carcinomas of the Lung and Prostate (clinicaltrials.gov)
    P1, N=12, Not yet recruiting, Memorial Sloan Kettering Cancer Center | Initiation date: Mar 2026 --> Jun 2026
    Trial initiation date
    |
    PTEN (Phosphatase and tensin homolog) • RB1 (RB Transcriptional Corepressor 1) • DLL3 (Delta Like Canonical Notch Ligand 3)
    |
    TP53 mutation • PTEN mutation • RB1 mutation • DLL3 expression
    13d
    Advances in Delta-like Ligand 3-Targeted Diagnosis and Treatment. (PubMed, Mol Pharm)
    The two modalities are mutually reinforcing and hold promise for advancing the precision diagnosis and clinical translation of DLL3-targeted strategies in NENs. This review summarizes recent key advancements in DLL3-targeted nuclear medicine and discusses future directions for DLL3 ImmunoPET imaging and TRT.
    Review • Journal
    |
    DLL3 (Delta Like Canonical Notch Ligand 3)
    |
    DLL3 expression
    14d
    Study of [212Pb]Pb-DOTAM-MAM279 ([212Pb]Pb-MP0712) in Patients With Small Cell Lung Cancer and Other DLL3 Expressing Solid Tumors (clinicaltrials.gov)
    P1/2, N=138, Recruiting, Molecular Partners AG | Initiation date: Jan 2026 --> Apr 2026
    Trial initiation date
    |
    DLL3 (Delta Like Canonical Notch Ligand 3)
    |
    DLL3 expression
    19d
    DAREON ® -Lung-1: A Study in People With Advanced Small Cell Lung Cancer to Compare Obrixtamig Plus Atezolizumab, Carboplatin, and Etoposide Treatment With Standard Chemotherapy (clinicaltrials.gov)
    P3, N=670, Not yet recruiting, Boehringer Ingelheim | Trial completion date: Apr 2029 --> Jul 2029
    Trial completion date
    |
    DLL3 (Delta Like Canonical Notch Ligand 3)
    |
    DLL3 expression
    |
    VENTANA DLL3 (SP347) Assay
    |
    Tecentriq (atezolizumab) • carboplatin • etoposide IV • obrixtamig (BI 764532)
    20d
    68Ga-PFD3 PET Imaging for the Diagnosis and Evaluation of Small Cell Lung Cancer (clinicaltrials.gov)
    P1/2, N=30, Recruiting, Peking University First Hospital
    New P1/2 trial
    |
    DLL3 (Delta Like Canonical Notch Ligand 3)
    |
    DLL3 expression
    25d
    Brief Report: Low Delta-like Ligand 3 expression and T Cell Exhaustion Drive Resistance to Tarlatamab combined with anti-PD-1 in Small-Cell Lung Cancer. (PubMed, J Thorac Oncol)
    Acquired resistance to tarlatamab plus anti-PD-1 in SCLC was associated with low DLL3 antigen expression particularly in the setting of phenotypic switch to a non-small cell lung cancer morphology and an increasingly immunosuppressive TME. Therefore, combination strategies that incorporate immune checkpoint blockade or myeloid-targeted therapies may be warranted to enhance treatment outcomes.
    Journal • PD(L)-1 Biomarker • IO biomarker
    |
    CD8 (cluster of differentiation 8) • LAG3 (Lymphocyte Activating 3) • CTLA4 (Cytotoxic T-Lymphocyte Associated Protein 4) • DLL3 (Delta Like Canonical Notch Ligand 3) • TIGIT (T Cell Immunoreceptor With Ig And ITIM Domains 2) • MRC1 (Mannose Receptor C-Type 1) • SYP (Synaptophysin)
    |
    DLL3 expression
    |
    Imdelltra (tarlatamab-dlle)
    27d
    Delta-like ligand 3 expression in isocitrate dehydrogenase-mutant and isocitrate dehydrogenase-wildtype glioma is largely retained at recurrence, supporting its potential as a therapeutic target. (PubMed, Neurooncol Adv)
    DLL3 expression level is retained or increased in the majority of recurrent gliomas. Inclusion in trials with DLL3-targeting agents in recurrent glioma based on primary tumor material is justified, depending on the required level of DLL3 positivity for inclusion.
    Journal
    |
    DLL3 (Delta Like Canonical Notch Ligand 3)
    |
    DLL3 expression • DLL3 positive • IDH wild-type
    27d
    Delta-like Ligand 3-Directed 225Ac Radioimmunotherapy in Neuroendocrine Lung and Prostate Cancer Models. (PubMed, J Nucl Med)
    Histopathologic assessment of background organs demonstrated mild to moderate kidney and ovary toxicity in the SC16 group compared with the highest-dose TDI-Y-010 cohort (37.0 kBq). [225Ac]Ac-mcp-TDI-Y-010 exhibited excellent antitumor efficacy with mild and transient hematologic toxicity, supporting its potential as a radioimmunotherapeutic agent for patients with DLL3-expressing neuroendocrine cancers.
    Preclinical • Journal
    |
    DLL3 (Delta Like Canonical Notch Ligand 3)
    |
    DLL3 expression • DLL3 positive
    1m
    SPECTRAL-1: A First-in-human (FIH), Phase 1 Study of ML261, an Autologous Potency Enhanced Anti-DLL3 CAR T Cell Therapy, in Participants With R/R SCLC or Select NECs (clinicaltrials.gov)
    P1, N=110, Not yet recruiting, Moonlight Bio, Inc
    New P1 trial • First-in-human
    |
    DLL3 (Delta Like Canonical Notch Ligand 3)
    |
    DLL3 expression
    1m
    DAREON ® -Lung-1: A Study in People With Advanced Small Cell Lung Cancer to Compare Obrixtamig Plus Atezolizumab, Carboplatin, and Etoposide Treatment With Standard Chemotherapy (clinicaltrials.gov)
    P3, N=670, Not yet recruiting, Boehringer Ingelheim
    New P3 trial
    |
    DLL3 (Delta Like Canonical Notch Ligand 3)
    |
    DLL3 expression
    |
    VENTANA DLL3 (SP347) Assay
    |
    Tecentriq (atezolizumab) • carboplatin • etoposide IV • obrixtamig (BI 764532)
    1m
    Clinical Utility of Transcriptomic Signatures to Identify Androgen Receptor and Neuroendocrine Signaling in Prostate Cancer. (PubMed, JCO Precis Oncol)
    Prostate cancer exhibits distinct molecular subtypes defined by AR signaling activity, NEPC transcriptional profiles, and genomic alterations. These biologically and clinically relevant subgroups provide a framework for precision oncology approaches and inform patient selection for biomarker-driven trials such as the ongoing PREDICT study (ClinicalTrials.gov identifier: NCT06632977).
    Journal
    |
    TP53 (Tumor protein P53) • PTEN (Phosphatase and tensin homolog) • AR (Androgen receptor) • DLL3 (Delta Like Canonical Notch Ligand 3) • FOLH1 (Folate hydrolase 1) • SPOP (Speckle Type BTB/POZ Protein)
    |
    PTEN mutation • DLL3 expression