# Datopotamab Deruxtecan in Advanced or Metastatic Non-Small Cell Lung Cancer With Actionable Genomic Alterations: Results From the Phase II TROPION-Lung05 Study

Source: https://onco.cc/key-papers/paper-tropion-lung05-j-clin-oncol-2025/  
OnCo record `paper-tropion-lung05-j-clin-oncol-2025` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Published report from the TROPION-Lung05 trial registered as NCT04484142, in Journal of Clinical Oncology (2025), chosen as the most cited paper whose own text cites the registry id.

## Summary

Purpose: Datopotamab deruxtecan (Dato-DXd) is a trophoblast cell-surface antigen-2-directed antibody-drug conjugate with a highly potent topoisomerase I inhibitor payload. The TROPION-Lung05 phase II trial (ClinicalTrials.gov identifier: NCT04484142) evaluated the safety and clinical activity of Dato-DXd in patients with advanced/metastatic non-small cell lung cancer (NSCLC) with actionable genomic alterations progressing on or after targeted therapy and platinum-based chemotherapy.

Patients and methods: Patients received Dato-DXd 6 mg/kg once every 3 weeks. The primary end point was objective response rate (ORR) by blinded independent central review. Secondary end points included duration of response (DOR), safety, tolerability, and survival.

Results: Among 137 patients who received at least 1 dose of Dato-DXd, 71.5% received at least three lines of prior therapies for advanced/metastatic disease. Overall, 56.9% had EGFR mutations and 24.8% had ALK rearrangements. Median treatment duration was 4.4 months (range, 0.7-20.6). The confirmed ORR was 35.8% (95% CI, 27.8 to 44.4) overall, and 43.6% (95% CI, 32.4 to 55.3) and 23.5% (95% CI, 10.7 to 41.2) in those with EGFR mutations and ALK rearrangements, respectively. The median DOR was 7.0 months (95% CI, 4.2 to 9.8), and the overall disease control rate was 78.8% (95% CI, 71.0 to 85.3). Grade ≥3 treatment-related adverse events (TRAEs) occurred in 28.5% of patients. The most common TRAE was stomatitis (preferred term; any grade: 56.2%; grade ≥3: 9.5%). Five (3.6%) patients experienced adjudicated treatment-related interstitial lung disease/pneumonitis, with 1 (0.7%) grade 5 event.

Conclusion: Encouraging and durable antitumor activity was observed with Dato-DXd in this heavily pretreated advanced/metastatic NSCLC population with actionable genomic alterations. The rate of treatment-related grade ≥3 toxicities was comparable with previous observations, and no new safety signals were observed.

Indexed on Europe PMC as PubMed record 39761483 (DOI 10.1200/jco-24-01349). Its abstract cites the registry id NCT04484142, which is how it was matched to this trial; no figure has been checked by an editor.

## Fields

- Kind: Key paper
- Last checked: 2026-09-22
- Tags: europepmc-ingest
- Journal: Journal of Clinical Oncology
- Year: 2025
- DOI: 10.1200/jco-24-01349
- Authors: Sands J, Ahn MJ, Lisberg A, et al.
- What it means: This is the paper Europe PMC returns for registry id NCT04484142 with the most citations, so it is the natural first reading for anyone following the TROPION-Lung05 trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.
- Caveats: Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.

## Sources

- J Clin Oncol 2025: https://doi.org/10.1200/jco-24-01349
- PubMed: https://pubmed.ncbi.nlm.nih.gov/39761483/
- Europe PMC: https://europepmc.org/article/MED/39761483
- ClinicalTrials.gov NCT04484142: https://clinicaltrials.gov/study/NCT04484142

## Connected records

- trials: [TROPION-Lung05](https://onco.cc/trials/tropion-lung05/)
- journals: [Journal of Clinical Oncology](https://onco.cc/journals/jco/)

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