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DRUG CLASS:

DLL3-targeted antibody-drug conjugate

3d
A novel nomogram based on DLL3 and PD-L1 for predicting the prognosis of patients with small cell lung cancer. (PubMed, BMC Cancer)
The prognostic model developed in this study offers predictive value in estimating 12-month survival probability for SCLC patients, aiding clinicians in making more informed treatment decisions.
Journal • PD(L)-1 Biomarker • IO biomarker
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PD-L1 (Programmed death ligand 1) • KIT (KIT proto-oncogene, receptor tyrosine kinase) • DLL3 (Delta Like Canonical Notch Ligand 3)
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PD-L1 expression • KIT expression
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Rova-T (rovalpituzumab tesirine)
2ms
New P3 trial
2ms
Evaluating BL-M14D1 in Subjects With Locally Advanced or Metastatic Small Cell Lung Cancer and Neuroendocrine Tumors (clinicaltrials.gov)
P1, N=120, Recruiting, SystImmune Inc. | Not yet recruiting --> Recruiting | Initiation date: Sep 2025 --> Apr 2025
Enrollment open • Trial initiation date
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DLL3 (Delta Like Canonical Notch Ligand 3)
2ms
Antibody Drugs Conjugates in Small-Cell Lung Cancer: Present-Day Status and Promises. (PubMed, Oncologist)
While ADCs have generated encouraging response rates in SCLC, durability has remained limited. Future development will require optimization of payloads, linkers, and trial design to determine whether ADCs can achieve a sustained role in this disease.
Journal
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CD276 (CD276 Molecule) • DLL3 (Delta Like Canonical Notch Ligand 3) • SEZ6 (Seizure Related 6 Homolog)
3ms
New P1/2 trial
4ms
A Trial of SHR-4849 Combined With Other Antitumor Drugs in Patients With Malignant Solid Tumors (clinicaltrials.gov)
P2, N=120, Recruiting, Suzhou Suncadia Biopharmaceuticals Co., Ltd. | Not yet recruiting --> Recruiting
Enrollment open
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cisplatin • carboplatin • CS1002 (ipilimumab biosimilar) • AiRuiLi (adebrelimab)
4ms
New P1 trial
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DLL3 (Delta Like Canonical Notch Ligand 3)
6ms
New P2 trial
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cisplatin • carboplatin • CS1002 (ipilimumab biosimilar) • AiRuiLi (adebrelimab)
6ms
Harnessing delta-like ligand 3: bridging biomarker discovery to next-generation immunotherapies in refractory small cell lung cancer. (PubMed, Front Immunol)
The 2024 FDA approval of tarlatamab-a bispecific T-cell engager (BiTE) targeting DLL3 and CD3-marks a pivotal advancement, demonstrating improvement in survival in refractory disease. This review examines three key advances reshaping SCLC management: (1) mechanistic links between DLL3-driven tumorigenesis and PD-L1-mediated immunosuppression, (2) clinical progress in antibody-drug conjugates (ADCs) with next-generation payloads (e.g., FZ-AD005), multispecific BiTEs (e.g., HPN328), and engineered CAR-T/NK cells with enhanced metabolic resilience, and (3) precision strategies combining liquid biopsy for dynamic DLL3 profiling with immuno-PET imaging using [89Zr]Zr-DFO-SC16. Emerging synergies, such as combining DLL3-targeted BiTEs with ICIs to amplify T-cell infiltration or reprogramming CAR-T mitochondrial metabolism, further underscore the potential of multimodal approaches. Together, these developments signal a transformative era in SCLC treatment, where molecular diagnostics and engineered immunotherapies converge to address unmet clinical needs.
Review • Journal • PD(L)-1 Biomarker • IO biomarker
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PD-L1 (Programmed death ligand 1) • DLL3 (Delta Like Canonical Notch Ligand 3)
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Imdelltra (tarlatamab-dlle) • gocatamig (MK-6070)
6ms
A Study of ZL-1310 in Participants With Selected Solid Tumors (clinicaltrials.gov)
P1/2, N=86, Recruiting, Zai Lab (Shanghai) Co., Ltd. | Not yet recruiting --> Recruiting
Enrollment open
8ms
Comparison of two immunotoxins against DLL3 receptor; as an inhibitor for small cell lung cancer. (PubMed, Front Mol Biosci)
In this study, we investigated the binding ability, cytotoxicity, apoptosis induction rate, and permeability of two immunotoxins based on the rovalpituzumab antibody...The designed immunotoxins in prokaryotic hosts exhibit good anticancer performance in A549 lung cancer cells. Additionally, the bacterial toxin-based immunotoxin has a greater ability to induce apoptosis compared to human enzymes and can be considered as a therapeutic option for SCLC cancer.
Journal
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DLL3 (Delta Like Canonical Notch Ligand 3)
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Rova-T (rovalpituzumab tesirine)
9ms
New P1/2 trial