Loading
A protein that appears on the surface of small-cell lung cancer cells, now hit by a drug that pulls T cells onto them. This dossier gathers the 6 products (1 approved), 26 trials, 4 pathways and 1 resistance route in the corpus that involve it, with external identifiers so it can be joined to UniProt, ChEMBL, Open Targets and the rest of biology.
Normally intracellular Golgi protein; ASCL1-driven neuroendocrine lineage exposes it on the membrane.
| Cancer | Prevalence | Measure | Note | Source |
|---|---|---|---|---|
| Small-cell lung cancer | 80-85% | IHC, any expression | Wikipedia | |
| Prostate cancer | 70-80% | Neuroendocrine prostate cancer only | Rare in adenocarcinoma | Wikipedia |
Approximate, population-level figures; the measure column says what was counted. Ranges show the midpoint as a bar.
| Modality | Approved | Phase 3 | Phase 2 | Withdrawn or failed |
|---|---|---|---|---|
| ADC 2 | - | - | ||
| T-cell engager 2 | - | - | ||
| Bispecific antibody 1 | - | - | - | |
| Cell therapy 1 | - | - | - |
| Trial | Setting | Result | Products | ||
|---|---|---|---|---|---|
DeLLphi-305 NCT06211036 | 3 | Positive | First-line maintenance in ES-SCLC after platinum-etoposide-durvalumab: tarlatamab + durvalumab vs durvalumab | Met the primary overall survival endpoint at the pre-specified interim analysis (Amgen, 8 September 2026); progression-free survival and response rate also improved; figures not yet disclosed. | |
DeLLphi-304 NCT05740566 | 3 | Positive | Second-line small-cell lung cancer: tarlatamab vs chemotherapy | OS HR 0.60. | |
| 3 | Completed | A Randomized, Open-Label, Multicenter, Phase 3 Study of Rovalpituzumab Tesirine Compared With Topotecan for Subjects With Advanced or Metastatic DLL3high Small Cell Lung Cancer (SCLC) Who Have First Disease Progression During or Following Front-Line Platinum-Based Chemotherapy (TAHOE) | - | ||
| 3 | - | A Randomized, Double-Blind, Placebo-Controlled Phase 3 Study of Rovalpituzumab Tesirine as Maintenance Therapy Following First-Line Platinum-Based Chemotherapy in Subjects With Extensive Stage Small Cell Lung Cancer (MERU) | - | ||
| 3 | Active | A Phase 3, Open Label, Multicenter, Randomized Study of First Line Tarlatamab in Combination With Durvalumab, Carboplatin and Etoposide Versus Durvalumab, Carboplatin and Etoposide in Untreated Extensive Stage Small-Cell Lung Cancer (DeLLphi-312) | - | ||
| 3 | Recruiting | A Randomized, Open-Label, Phase 3 Study of ZL-1310, a DLL3 Antibody-Drug Conjugate (ADC), Compared to Investigator's Choice Therapy in Participants With Relapsed Small Cell Lung Cancer | - | ||
| 3 | Recruiting | DAREON ® -Lung-1: A Phase III Multi-center, Open-label, Randomised Trial of Intravenous Obrixtamig in Combination With Atezolizumab, Carboplatin, and Etoposide vs. Atezolizumab, Carboplatin, and Etoposide as First-line Treatment in Patients With Extensive-stage Small Cell Lung Cancer | - | ||
| 3 | Recruiting | A Phase III, Multi-center, Open-label, Randomised, Controlled Trial of Intravenous Obrixtamig in Combination With Carboplatin and Etoposide vs. Carboplatin and Etoposide as First-line Therapy in DLL3-positive Patients With Unresectable Locally Advanced or Metastatic Extrapulmonary Neuroendocrine Carcinomas | - | ||
| 3 | Recruiting | A Phase 3, Open-Label, Multicenter, Randomized Study of Subcutaneous vs Intravenous Tarlatamab in Participants With Relapsed Extensive-Stage Small Cell Lung Cancer After Platinum-based First-line Chemotherapy (DeLLphi-315) | - | ||
| 3 | Active | A Phase 3, Randomized, Double-blind, Placebo-controlled, Multicenter Study of Tarlatamab Therapy in Subjects With Limited-Stage Small-Cell Lung Cancer (LS-SCLC) Who Have Not Progressed Following Concurrent Chemoradiation Therapy | - | ||
| 3 | Planned | Phase III Trial of Consolidation Tarlatamab + Durvalumab vs. Durvalumab Alone for Limited-Stage-Small Cell Lung Cancer (LS-SCLC) | - | ||
| 2 | Active | Phase 2a Study Evaluating the Efficacy, Safety, Tolerability and Pharmacokinetics of Tarlatamab in Chinese Subjects With Advanced Small Cell Lung Cancer After Two or More Prior Lines of Treatment (DeLLphi-307) | - | ||
| 2 | Active | A Phase 2 Study Evaluating the Efficacy, Safety, Tolerability, and Pharmacokinetics of Tarlatamab in Subjects With Relapsed/Refractory Small Cell Lung Cancer After Two or More Prior Lines of Treatment (DeLLphi-301). | Objective response 40 percent at the 10 mg dose and 32 percent at 100 mg in previously treated small-cell lung cancer; median progression-free survival 4.9 and 3.9 months. | ||
| 2 | Completed | An Open-label, Single-Arm, Phase 2 Study Evaluating the Efficacy, Safety and Pharmacokinetics of Rovalpituzumab Tesirine (SC16LD6.5) for Third-line and Later Treatment of Subjects With Relapsed or Refractory Delta-Like Protein 3-Expressing Small Cell Lung Cancer (TRINITY) | - | ||
| 2 | Active | A Phase 2, Open-label, Randomized, Multicenter Study of Tarlatamab Dosing Regimens in Subjects With Small Cell Lung Cancer (SCLC) (DeLLphi-309) | - | ||
| 2 | Recruiting | A Multicentre Phase II Trial of Tarlatamab in Patients With Pretreated Extensive-stage Small Cell Lung Cancer (ES-SCLC) and ECOG PS 2 | - | ||
| 2 | Recruiting | DAREON™-5: An Open-label, Multi-center Phase II Dose Selection Trial of Intravenous BI 764532, a DLL3-targeting T Cell Engager, in Patients With Relapsed/Refractory Extensive-stage Small Cell Lung Cancer and in Patients With Other Relapsed/Refractory Neuroendocrine Carcinomas | - | ||
| 2 | Recruiting | Phase 2, Multicenter, Open Label, Platform Study Investigating Tarlatamab (AMG 757) in Patients With Metastatic/Locally Advanced Small-Cell Lung Cancer (SCLC) and Other Poorly Differentiated Neuroendocrine Carcinomas (NECs), With Biomarker Analysis to Characterize Response/Resistance | - | ||
| 2 | Recruiting | A Front-Line Window-of-Opportunity Phase 2 Study of Tarlatamab (Bispecific T Cell Engager: DLL3-CD3) in Patients With Extensive-Stage Small-Cell Lung Cancer | - | ||
| 1/2 | Recruiting | An Open-label, Multicenter, Dose Escalation, and Dose Expansion Phase 1/2 Study With Peluntamig (PT217) Followed by a Key ChemotherapY and/or Checkpoint Inhibitor ComBination in Patients With NeuRoendocrIne Carcinomas That Are Known to be DLL3 expressinG CancErs (SKYBRIDGE) | - | ||
| 1/2 | Recruiting | A Phase 1b/2, Open-label, Multi-center Study of ZL-1310 in Participants With Selected Solid Tumors | - | ||
| 1/2 | Recruiting | A Phase I/II Open-label Study of DJI136, a DLL3-targeted CAR-T Therapy, in Adult Patients With ES-SCLC | - | ||
| 1/2 | Recruiting | A Phase 1/2 Adaptive Dose-Escalation and Expansion Study of Dual-Targeting Chimeric Antigen Receptor Natural Killer (CAR-NK) Cells Directed Against DLL3, CD56 (NCAM1), and/or GD2 in Adults With Relapsed/Refractory Small Cell Lung Cancer | - | - | |
| 1/2 | Recruiting | A Phase 1/2 Adaptive Dose-Escalation and Expansion Study of Dual-Targeting Chimeric Antigen Receptor Natural Killer (CAR-NK) Cells Directed Against DLL3, CD56 (NCAM1), and/or GD2 in Adults With Relapsed/Refractory Small Cell Lung Cancer | - | - | |
| 1/2 | Planned | A Phase Ib/II, Open-label, Safety and Tolerability Trial of Obrixtamig in Combination With ZL-1310 in Patients With Poorly Differentiated NEC | - | ||
| 1/2 | Recruiting | RAdiation comBined With BIspecific T-Cell Engager in DLL3 Expressing Tumors (RABBIT) Study: A Phase I/II Study of AMG757 / Tarlatamab and Concurrent Radiation Therapy in Tumors With High Prevalence of DLL3 | - |
RB1/TP53 loss enables transdifferentiation; AR-indifferent, DLL3-positive, PSMA-negative.
Some cancer cells behave like stem cells: they can regrow the whole tumour, resist treatment, and switch identities. This plasticity explains why tumours come back and why some lung and prostate cancers transform into a different cancer type under therapy.
Which nodes have drugs →Under pressure from a drug that blocks its identity (the androgen receptor in prostate cancer, EGFR in lung cancer), a tumour can change what kind of cell it is, becoming a small-cell neuroendocrine cancer that no longer needs the blocked signal. It is the ultimate escape: not a new mutation in the engine, but a new engine.
Which nodes have drugs →A cell-to-cell contact signal that decides cell fate. It drives T-cell leukaemia when mutated on, acts as a tumour suppressor in some squamous cancers when lost, and its ligand DLL3 became a drug target in small-cell lung cancer.
Which nodes have drugs →When a drug blocks a cancer's engine, the cancer has five ways back: change the part the drug binds, make more of it, take a side road, switch to a different engine altogether, or stop letting the drug in. Knowing which route a tumour took decides the next drug.
Which nodes have drugs →No companion diagnostic in the registry measures this target.
No model entry for this target yet; check the cancer entries on the models page.
Why unresolved. DeLLphi-304 proved second-line benefit; DeLLphi-305 tests first-line maintenance with durvalumab. DLL3 is not tested before treatment, yet expression varies by ASCL1 subtype and falls with plasticity.
What would answer it. DeLLphi-305 overall survival with subtype and DLL3 IHC analysed prospectively.
Query for this target: (TITLE:"DLL3" OR ABSTRACT:"DLL3") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about DLL3, not a curated reading list.
The dossier as machine-readable JSON, at /api/v1/dossiers/dll3.json: identifiers from HGNC, Ensembl, UniProt and ChEMBL, products with status, trials, pathways, hotspots, open questions and assays. The full entity record is in the open API at /api/v1/entities/dll3.json. Licence CC BY-NC 4.0.