# Tarlatamab for patients with previously treated small-cell lung cancer

Source: https://onco.cc/key-papers/paper-ahn-dellphi-301-tarlatamab-sclc-nejm-2023/  
OnCo record `paper-ahn-dellphi-301-tarlatamab-sclc-nejm-2023` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

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.

## Fields

- Kind: Key paper
- Last checked: 2026-09-25
- Tags: lung-evidence
- Journal: New England Journal of Medicine
- Year: 2023
- DOI: 10.1056/NEJMoa2307980
- Authors: Ahn MJ, Cho BC, Felip E, et al.
- 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.
- What it means: 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.

## Sources

- N Engl J Med 2023: https://doi.org/10.1056/NEJMoa2307980
- PubMed: https://pubmed.ncbi.nlm.nih.gov/37861218/
- ClinicalTrials.gov NCT05060016: https://clinicaltrials.gov/study/NCT05060016

## Connected records

- key papers: [Comprehensive genomic profiles of small cell lung cancer](https://onco.cc/key-papers/paper-george-sclc-genomic-profiles-nature-2015/), [Durvalumab plus platinum-etoposide versus platinum-etoposide in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN)](https://onco.cc/key-papers/paper-paz-ares-caspian-durvalumab-es-sclc-lancet-2019/), [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](https://onco.cc/key-papers/paper-dll3-sclc-clin-cancer-res-2019/), [Molecular subtypes of small cell lung cancer: a synthesis of human and mouse model data](https://onco.cc/key-papers/paper-rudin-sclc-molecular-subtypes-nat-rev-cancer-2019/), [Tarlatamab in Small-Cell Lung Cancer after Platinum-Based Chemotherapy](https://onco.cc/key-papers/paper-tarlatamab-sclc-n-engl-j-med-2025/)
- cancers: [Extensive-stage small-cell lung cancer](https://onco.cc/cancers/extensive-stage-sclc/), [Lung cancer (all types)](https://onco.cc/cancers/lung-cancer/), [Small-cell lung cancer](https://onco.cc/cancers/sclc/)
- fronts: [Drug Discovery Platforms](https://onco.cc/fronts/drug-discovery/), [Immunotherapy](https://onco.cc/fronts/immunotherapy/)
- technologies: [T-cell engagers (bispecific)](https://onco.cc/technologies/t-cell-engager/)
- targets: [DLL3](https://onco.cc/targets/dll3/)
- drugs: [Tarlatamab](https://onco.cc/drugs/tarlatamab/)
- companies: [Amgen](https://onco.cc/companies/amgen/)
- terms: [Drug resistance (primary and acquired)](https://onco.cc/terms/resistance/)
- trials: [DeLLphi-304](https://onco.cc/trials/dellphi-304/)
- people: [Luis Paz-Ares](https://onco.cc/people/luis-paz-ares/)
- bottlenecks: [Fragmented care and guideline gaps](https://onco.cc/bottlenecks/b-care-fragmentation/), [Manufacturing cost and time for living and radioactive medicines](https://onco.cc/bottlenecks/b-manufacturing-cell-therapy/), [Rare and paediatric cancers without markets](https://onco.cc/bottlenecks/b-rare-cancers/), [Toxicity and quality of life are undervalued](https://onco.cc/bottlenecks/b-toxicity-qol/)
- journals: [New England Journal of Medicine](https://onco.cc/journals/nejm/)
- roadmaps: [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](https://onco.cc/roadmaps/lung-cancer-evidence-roadmap/)
- ideas: [Run small-cell lung cancer as one platform with shared controls and subtype stratification](https://onco.cc/ideas/idea-lung-small-cell-platform-with-shared-controls-and-subtypes/)

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