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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.
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.
DLL3 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.
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.
One of the most cited trial reports Europe PMC returns for Tarlatamab in Small-cell lung cancer, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.
Immunotherapy is now part of first-line treatment for extensive-stage small-cell lung cancer everywhere, on the strength of a gain measured in weeks. The size of that gain is the reason small-cell lung cancer remains the clearest unmet need in thoracic oncology.
The organising framework for every small-cell lung cancer trial designed since. It is also why the slow progress in the disease is now attributed to treating four diseases as one rather than to the biology being intractable.
Why small-cell lung cancer has no targeted therapy in the conventional sense: it is built from the loss of TP53 and RB1, and the drugs that transformed non-small-cell disease inhibit gains rather than restore losses. The NOTCH result pointed at DLL3 and, eventually, at tarlatamab.
Shares Durvalumab plus platinum-etoposide versus platinum-etoposide in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN), 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, Rare and paediatric cancers without markets, New England Journal of Medicine and the tag lung-evidence.
Shares 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, Extensive-stage small-cell lung cancer, Toxicity and quality of life are undervalued, New England Journal of Medicine and the tag lung-evidence.
Shares Luis Paz-Ares, Amgen, 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, Drug resistance (primary and acquired) and the tag lung-evidence.
Shares 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, Toxicity and quality of life are undervalued, New England Journal of Medicine, Lung cancer (all types) and the tag lung-evidence.
Shares 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, Drug resistance (primary and acquired), Toxicity and quality of life are undervalued, New England Journal of Medicine and the tag lung-evidence.
Shares 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, Drug resistance (primary and acquired), Toxicity and quality of life are undervalued, New England Journal of Medicine and the tag lung-evidence.
Shares Molecular subtypes of small cell lung cancer: a synthesis of human and mouse model data, 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, Drug resistance (primary and acquired), Lung cancer (all types) and the tag lung-evidence.
Shares 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, Fragmented care and guideline gaps, Lung cancer (all types), Small-cell lung cancer and the tag lung-evidence.