# Final Analysis Results and Patient-Reported Outcomes From DESTINY-Lung02-A Dose-Blinded, Randomized, Phase 2 Study of Trastuzumab Deruxtecan in Patients With HER2-Mutant Metastatic NSCLC

Source: https://onco.cc/key-papers/paper-destiny-lung02-j-thorac-oncol-2025/  
OnCo record `paper-destiny-lung02-j-thorac-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 DESTINY-Lung02 trial registered as NCT04644237, in Journal of Thoracic Oncology (2025), chosen as the most cited paper whose own text cites the registry id.

## Summary

Introduction: Trastuzumab deruxtecan (T-DXd) demonstrated strong and durable responses in patients with previously treated HER2 (ERBB2) mutant (HER2m) metastatic NSCLC (mNSCLC) in the DESTINY-Lung02 primary analysis (December 23, 2022, data cutoff). This final analysis evaluated T-DXd efficacy and safety after 8 additional months of follow-up, including clinically relevant subgroups and patient-reported outcomes.

Methods: DESTINY-Lung02 was a randomized, dose-blinded, multicenter, phase 2 trial. Patients with previously treated HER2m mNSCLC were randomized 2:1 to receive T-DXd 5.4 or 6.4 mg/kg once every 3 weeks. Primary end point was confirmed objective response rate by blinded independent central review.

Results: at August 25, 2023, 102 and 50 patients had received T-DXd 5.4 or 6.4 mg/kg, respectively. Median follow-up (Q1-Q3) was 15.8 (8.2-20.7) months and 16.5 (9.4-20.8) months, respectively. Confirmed objective response rate (95% confidence interval) was 50.0% (51/102; 39.9%-60.1%) and 56.0% (28/50; 41.3%-70.0%), respectively. Safety profile was acceptable and generally manageable. Accordingly, median treatment duration (Q1-Q3) was 7.7 (3.7-14.4) months and 8.3 (2.8-13.1) months; drug-related grade 3 or higher treatment-emergent adverse events occurred in 39.6% (40/101) and 60.0% (30/50), with nausea most common (67.3% [68/101], 82.0% [41/50]). Adjudicated drug-related interstitial lung disease occurred in 14.9% (15/101) and 32.0% (16/50), mostly grade 1 or 2 with one grade 5 in each arm. Health-related quality of life was preserved for the duration of T-DXd treatment while sample size was sufficient for analysis, with no adverse effects on health-related quality of life observed at either dose.

Conclusions: T-DXd demonstrated strong and durable responses at both doses, with no clinically significant changes in toxicity. The approved 5.4-mg/kg dose demonstrated a more favorable benefit-risk profile, including lower adjudicated drug-related interstitial lung disease incidence.

Gov identifier: NCT04644237.

Indexed on Europe PMC as PubMed record 40749900 (DOI 10.1016/j.jtho.2025.07.129). Its abstract cites the registry id NCT04644237, 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 Thoracic Oncology
- Year: 2025
- DOI: 10.1016/j.jtho.2025.07.129
- Authors: Jänne PA, Goto Y, Kubo T, et al.
- What it means: This is the paper Europe PMC returns for registry id NCT04644237 with the most citations, so it is the natural first reading for anyone following the DESTINY-Lung02 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 Thorac Oncol 2025: https://doi.org/10.1016/j.jtho.2025.07.129
- PubMed: https://pubmed.ncbi.nlm.nih.gov/40749900/
- Europe PMC: https://europepmc.org/article/MED/40749900
- ClinicalTrials.gov NCT04644237: https://clinicaltrials.gov/study/NCT04644237

## Connected records

- trials: [DESTINY-Lung02](https://onco.cc/trials/destiny-lung02/)
- journals: [Journal of Thoracic Oncology](https://onco.cc/journals/journal-of-thoracic-oncology/)

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