{"entity":{"id":"paper-ahn-dellphi-301-tarlatamab-sclc-nejm-2023","kind":"paper","name":"Tarlatamab for patients with previously treated small-cell lung cancer","aka":[],"tldr":"The first drug in decades built specifically for small-cell lung cancer. Tarlatamab grabs a protein called DLL3 on the tumour with one arm and a T cell with the other; 40 percent of heavily pretreated patients responded.","summary":"The DeLLphi-301 investigators, reported by Ahn, Cho, Felip and colleagues with Paz-Ares as senior author, gave tarlatamab, a bispecific T-cell engager targeting delta-like ligand 3 and CD3, intravenously every two weeks at 10 mg or 100 mg to 220 patients with previously treated small-cell lung cancer, a median of two prior lines. The primary endpoint was objective response by blinded independent central review.\n\nDLL3 is expressed on most small-cell tumours and almost nowhere in normal adult tissue, which is why it is the target the field converged on after antibody-drug conjugates against it failed. The phase 3 confirmation, DeLLphi-304, is held in the corpus as paper-tarlatamab-sclc-n-engl-j-med-2025.","asOf":"2026-09-25","links":[{"label":"N Engl J Med 2023","url":"https://doi.org/10.1056/NEJMoa2307980"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/37861218/"},{"label":"ClinicalTrials.gov NCT05060016","url":"https://clinicaltrials.gov/study/NCT05060016"}],"tags":["lung-evidence"],"related":["paper-tarlatamab-sclc-n-engl-j-med-2025","paper-dll3-sclc-clin-cancer-res-2019","paper-rudin-sclc-molecular-subtypes-nat-rev-cancer-2019"],"cancers":["lung-cancer","sclc","extensive-stage-sclc"],"sections":["immunotherapy","drug-discovery"],"technologies":["t-cell-engager"],"targets":["dll3"],"drugs":["tarlatamab"],"companies":["amgen"],"institutions":[],"pathways":[],"terms":["resistance"],"trials":["dellphi-304"],"people":["luis-paz-ares"],"bottlenecks":["b-rare-cancers","b-toxicity-qol","b-manufacturing-cell-therapy","b-care-fragmentation"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2023,"doi":"10.1056/NEJMoa2307980","pmid":"37861218","authors":"Ahn MJ, Cho BC, Felip E, et al.","paperType":"rct","findings":["Objective response in 40 percent (97.5 percent confidence interval 29 to 52) of the 10 mg group and 32 percent (21 to 44) of the 100 mg group.","Duration of response was at least 6 months in 59 percent of responders (40 of 68 patients).","Median progression-free survival 4.9 months (95 percent confidence interval 2.9 to 6.7) at 10 mg and 3.9 months (2.6 to 4.4) at 100 mg; estimated 9-month overall survival 68 percent and 66 percent.","Cytokine release syndrome in 51 percent at 10 mg and 61 percent at 100 mg, primarily during cycle 1 and mostly grade 1 or 2; grade 3 in 1 percent at 10 mg against 6 percent at 100 mg.","Decreased appetite in 29 and 44 percent and pyrexia in 35 and 33 percent; 3 percent discontinued for treatment-related adverse events."],"whatItMeans":"Small-cell lung cancer got its first targeted drug, and the mechanism is a T-cell engager rather than a kinase inhibitor. It also brought cytokine release syndrome, and the inpatient monitoring that goes with it, into thoracic oncology for the first time.","caveats":["Single-arm phase 2 with response as the endpoint; the randomised comparison against chemotherapy is DeLLphi-304.","Cytokine release syndrome in more than half of patients requires step-up dosing and monitoring that many centres are not set up to provide.","Responses are real but short: median progression-free survival is under five months.","DLL3 expression was not used to select patients, so who benefits within the DLL3-positive population is unknown."],"changedPractice":true,"participants":220},"route":"/key-papers/paper-ahn-dellphi-301-tarlatamab-sclc-nejm-2023/","neighbours":{"paper":[{"id":"paper-george-sclc-genomic-profiles-nature-2015","kind":"paper","name":"Comprehensive genomic profiles of small cell lung cancer","route":"/key-papers/paper-george-sclc-genomic-profiles-nature-2015/"},{"id":"paper-paz-ares-caspian-durvalumab-es-sclc-lancet-2019","kind":"paper","name":"Durvalumab plus platinum-etoposide versus platinum-etoposide in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN)","route":"/key-papers/paper-paz-ares-caspian-durvalumab-es-sclc-lancet-2019/"},{"id":"paper-dll3-sclc-clin-cancer-res-2019","kind":"paper","name":"Efficacy and Safety of Rovalpituzumab Tesirine in Third-Line and Beyond Patients with DLL3-Expressing, Relapsed/Refractory Small-Cell Lung Cancer: Results From the Phase II TRINITY Study","route":"/key-papers/paper-dll3-sclc-clin-cancer-res-2019/"},{"id":"paper-rudin-sclc-molecular-subtypes-nat-rev-cancer-2019","kind":"paper","name":"Molecular subtypes of small cell lung cancer: a synthesis of human and mouse model data","route":"/key-papers/paper-rudin-sclc-molecular-subtypes-nat-rev-cancer-2019/"},{"id":"paper-tarlatamab-sclc-n-engl-j-med-2025","kind":"paper","name":"Tarlatamab in Small-Cell Lung Cancer after Platinum-Based Chemotherapy","route":"/key-papers/paper-tarlatamab-sclc-n-engl-j-med-2025/"}],"cancer":[{"id":"extensive-stage-sclc","kind":"cancer","name":"Extensive-stage small-cell lung cancer","route":"/cancers/extensive-stage-sclc/"},{"id":"lung-cancer","kind":"cancer","name":"Lung cancer (all types)","route":"/cancers/lung-cancer/"},{"id":"sclc","kind":"cancer","name":"Small-cell lung cancer","route":"/cancers/sclc/"}],"section":[{"id":"drug-discovery","kind":"section","name":"Drug Discovery Platforms","route":"/fronts/drug-discovery/"},{"id":"immunotherapy","kind":"section","name":"Immunotherapy","route":"/fronts/immunotherapy/"}],"technology":[{"id":"t-cell-engager","kind":"technology","name":"T-cell engagers (bispecific)","route":"/technologies/t-cell-engager/"}],"target":[{"id":"dll3","kind":"target","name":"DLL3","route":"/targets/dll3/"}],"drug":[{"id":"tarlatamab","kind":"drug","name":"Tarlatamab","route":"/drugs/tarlatamab/"}],"company":[{"id":"amgen","kind":"company","name":"Amgen","route":"/companies/amgen/"}],"term":[{"id":"resistance","kind":"term","name":"Drug resistance (primary and acquired)","route":"/terms/resistance/"}],"trial":[{"id":"dellphi-304","kind":"trial","name":"DeLLphi-304","route":"/trials/dellphi-304/"}],"person":[{"id":"luis-paz-ares","kind":"person","name":"Luis Paz-Ares","route":"/people/luis-paz-ares/"}],"bottleneck":[{"id":"b-care-fragmentation","kind":"bottleneck","name":"Fragmented care and guideline gaps","route":"/bottlenecks/b-care-fragmentation/"},{"id":"b-manufacturing-cell-therapy","kind":"bottleneck","name":"Manufacturing cost and time for living and radioactive medicines","route":"/bottlenecks/b-manufacturing-cell-therapy/"},{"id":"b-rare-cancers","kind":"bottleneck","name":"Rare and paediatric cancers without markets","route":"/bottlenecks/b-rare-cancers/"},{"id":"b-toxicity-qol","kind":"bottleneck","name":"Toxicity and quality of life are undervalued","route":"/bottlenecks/b-toxicity-qol/"}],"journal":[{"id":"nejm","kind":"journal","name":"New England Journal of Medicine","route":"/journals/nejm/"}],"roadmap":[{"id":"lung-cancer-evidence-roadmap","kind":"roadmap","name":"Lung cancer roadmap: from Doll and Hill and the naming of tobacco, through the cytotoxic plateau, computed tomography screening, EGFR and ALK, immunotherapy by PD-L1, the perioperative trials and PACIFIC, to DLL3 in small-cell disease and a 2032 registry watch","route":"/roadmaps/lung-cancer-evidence-roadmap/"}],"idea":[{"id":"idea-lung-small-cell-platform-with-shared-controls-and-subtypes","kind":"idea","name":"Run small-cell lung cancer as one platform with shared controls and subtype stratification","route":"/ideas/idea-lung-small-cell-platform-with-shared-controls-and-subtypes/"}]}}