T-DXd shows 56.9% response rate in China HER2-mutant lung cancer trial
Final DESTINY-Lung05 data show trastuzumab deruxtecan produced durable responses in pretreated HER2-mutant NSCLC, with no new safety signals beyond known interstitial lung disease risk.
Executive Summary
- A single-arm Phase 2 study in China asked whether trastuzumab deruxtecan produces durable tumor responses in patients with HER2-mutant non-small cell lung cancer who had already progressed on prior therapy.
- More than half of patients had a confirmed response, and that response held up with extended follow-up, reinforcing the efficacy basis for the drug's existing approval in this setting.
- Over half of patients had a severe drug-related adverse event, and roughly one in eight developed lung inflammation tied to the drug, a recognized risk for this antibody-drug conjugate class that clinicians already monitor for.
- The data affirm rather than newly establish the drug's role for this population, extending the evidence base behind a treatment already in use in China.
The finding
Trastuzumab deruxtecan, sold as Enhertu, was already approved in China in October 2024 for previously treated HER2-mutant metastatic non-small cell lung cancer, based on interim results from DESTINY-Lung02 and DESTINY-Lung05. The newly published final analysis of DESTINY-Lung05 (NCT05246514) reports mature outcomes from that same trial: as of the November 4, 2024 data cutoff, 72 patients had received the drug at 5.4 mg/kg every three weeks, with a median follow-up of 20.2 months, ranging from 2 to 27 months. The confirmed objective response rate by independent central review was 56.9%, with a 95% confidence interval of 44.7% to 68.6%. Trastuzumab+1Trastuzumab Deruxtecan in Patients From China With Pretreated HER2-Mutant Non-Small Cell Lung Cancer: Final Analysis of the Phase 2, Single-Arm DESTINY-Lung05 Trial.Jul 21, 2026A Single Arm Phase 2 Study to Evaluate Efficacy and Safety of Trastuzumab Deruxtecan for Patients With HER2 Mutant NSCLCNCT05246514
Probability of SuccessBased on the AppliedXL Probability of Success model. For more information about the methodology, read the research here.
How it was done
DESTINY-Lung05 is an open-label, single-arm, multicenter Phase 2 study conducted at sites in China. It enrolled patients with metastatic non-squamous NSCLC carrying a centrally confirmed HER2 exon 19 or 20 mutation who had relapsed on or were refractory to at least one prior line of anticancer therapy, had a WHO or ECOG performance status of 0 or 1, and a left ventricular ejection fraction of at least 50%. All patients received trastuzumab deruxtecan intravenously every three weeks. The primary endpoint was confirmed objective response rate by RECIST 1.1 as assessed by independent central review; progression-free survival, overall survival, and safety were secondary endpoints. NCT05246514+1A Single Arm Phase 2 Study to Evaluate Efficacy and Safety of Trastuzumab Deruxtecan for Patients With HER2 Mutant NSCLCNCT05246514Trastuzumab Deruxtecan in Patients From China With Pretreated HER2-Mutant Non-Small Cell Lung Cancer: Final Analysis of the Phase 2, Single-Arm DESTINY-Lung05 Trial.Jul 21, 2026
Durability and survival
Median progression-free survival by independent central review was 9.9 months (95% CI, 7.1 to 16.5), and median overall survival reached 21.0 months (95% CI, 17.5 to not calculable). Those figures sit alongside the response-rate result as the durability evidence behind the trial's design intent: a single-arm study cannot establish a survival benefit relative to a comparator, but the maturity of this follow-up, close to two years, gives the response and survival estimates more weight than an interim readout would carry. TrastuzumabTrastuzumab Deruxtecan in Patients From China With Pretreated HER2-Mutant Non-Small Cell Lung Cancer: Final Analysis of the Phase 2, Single-Arm DESTINY-Lung05 Trial.Jul 21, 2026
Safety
Grade 3 or higher drug-related adverse events occurred in 40 of 72 patients, or 55.6%. Adjudicated drug-related interstitial lung disease or pneumonitis, a known risk for this antibody-drug conjugate class, occurred in 9 patients (12.5%): eight were grade 1 or 2 and one was grade 3. The published analysis reported no new safety signals beyond this pattern. TrastuzumabTrastuzumab Deruxtecan in Patients From China With Pretreated HER2-Mutant Non-Small Cell Lung Cancer: Final Analysis of the Phase 2, Single-Arm DESTINY-Lung05 Trial.Jul 21, 2026
Prior evidence and precedent
The result extends, rather than departs from, earlier trials of the same drug in HER2-mutant NSCLC. In the terminated DESTINY-Lung01 trial, the HER2-positive (IHC3+) NSCLC subgroup showed a confirmed ORR of 52.9% with a median duration of response of 6.9 months. An interim analysis of the completed DESTINY-Lung02 trial's 5.4 mg/kg cohort reported a confirmed ORR of 57.7% with a median duration of response of 8.7 months. The DESTINY-Lung05 final analysis lands within that established response-rate band and adds substantially longer follow-up on survival and duration of response than either predecessor disclosed.
This analysis was produced using AI-assisted reporting systems, AppliedXL data, and official public records. These systems undergo editorial review, quality checks, and regular audits by human experts. Errors may still occur, as with any automated system. Always consult the linked primary sources. Read our AI Editorial Policy.