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A bispecific antibody that pulls T cells onto small-cell lung cancer cells produced responses in 40% of patients whose cancer had come back after chemotherapy, lasting far longer than any previous drug in this setting.
Open-label phase 2 trial of 220 patients with small-cell lung cancer that had progressed after platinum-based chemotherapy (and usually immunotherapy), testing tarlatamab, a DLL3 x CD3 bispecific T-cell engager, at 10 mg or 100 mg every two weeks. Primary endpoint was objective response rate.
At 10 mg the response rate was 40%, median PFS 4.9 months and median OS 14.3 months, with cytokine release syndrome in about half of patients, mostly grade 1-2 and mainly during the first cycle. It led to accelerated FDA approval in 2024 and was confirmed by the phase 3 DeLLphi-304 trial, which showed a survival benefit over chemotherapy (median OS 13.6 vs 8.3 months, HR 0.60).
Patients with small-cell lung cancer that has relapsed after chemotherapy now have a drug that works far better than topotecan or lurbinectedin, and it is the first T-cell engager approved for a solid tumour. Treatment requires inpatient monitoring for the first doses because of cytokine release syndrome, which most centres now manage on a short-stay basis. It does not yet apply to first-line treatment, where trials are ongoing.
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 A Phase 2 Study of Tarlatamab in Patients With Small Cell Lung Cancer (SCLC), DLL3, Tarlatamab, Amgen.
Shares DeLLphi-304, Molecular subtypes of small cell lung cancer: a synthesis of human and mouse model data, DLL3, Tarlatamab.
Shares Luis Paz-Ares, Objective response rate (ORR), Accelerated approval, Amgen.
Shares Objective response rate (ORR), CD3, Cytokine release syndrome (CRS), Wrong doses.
Shares Fiona Blackhall, Luis Paz-Ares, Subtype-directed therapy for SCLC (ASCL1 / NEUROD1 / POU2F3 / inflamed), DeLLphi-304.
Shares ICANS (neurotoxicity), Tarlatamab, Cytokine release syndrome (CRS), Extensive-stage small-cell lung cancer.
Shares ICANS (neurotoxicity), Objective response rate (ORR), CD3, Cytokine release syndrome (CRS).
Shares Objective response rate (ORR), CD3, Cytokine release syndrome (CRS), Wrong doses.