HER2-mutant Non-Small Cell Lung CancerPhase 2DL-05NCT05246514

A Single Arm Phase 2 Study to Evaluate Efficacy and Safety of Trastuzumab Deruxtecan for Patients With HER2 Mutant NSCLC

A Phase 2 study testing Trastuzumab deruxtecan in people with HER2-mutant Non-Small Cell Lung Cancer, run by AstraZeneca at 28 sites in China.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record

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Trial summary

The purpose of this study is to evaluate the efficacy and safety of T-DXd in participants with HER2 mutant metastatic non-squamous NSCLC. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: HER2-mutant Non-Small Cell Lung Cancer
What is being tested?: Trastuzumab deruxtecan
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 72 participants
Where: 28 sitesChina
Study dates: 13 Jul 2022to 31 Dec 2026
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Pathologically documented metastatic non-squamous NSCLC.
Has relapsed from or is refractory to at least one-line of anticancer treatment.
Documented HER2 exon 19 or 20 mutation from central FFPE tumour tissue testing.
WHO or ECOG performance status of 0 or 1.
Presence of at least one measurable lesion assessed by the investigator based on RECIST 1.1.
LVEF ≥ 50% within 28 days before enrolment.

Who cannot join

Mixed small cell lung cancer, squamous histology NSCLC, and sarcomatoid histology variant NSCLC.
Corrected QT interval (QTcF) prolongation to > 470 ms (females) or > 450 ms (males), based on average of the screening triplicate 12-lead ECG.
History of (non-infectious) ILD/pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening.
Has unresolved toxicities from previous anticancer therapy, defined as toxicities (excluding alopecia) not yet resolved to Grade ≤1 or baseline. Participants with clinically stable chronic Grade 2 toxicity not reasonably expected to be exacerbated by study intervention may be included only after consultation with the AstraZeneca study physician or designee.
Has been previously treated with HER2-targeted therapies, except for pan-HER class TKIs or has received prior treatment with an ADC which consists of an exatecan derivative that is a topoisomerase I inhibitor.

Trial locations and contacts

28 sites in 1 country.

City, postcode or hospital

28 sites in 1 country

China28 sites

Research Site
Baoding, 071000
Research Site
Beijing, 100142
Research Site
Beijing, 100191
Research Site
Changchun, 130000
Research Site
Changsha, 410008
Research Site
Changsha, 410013
Research Site
Chengdu, 610041
Research Site
Chongqing, 400030
Research Site
Guangzhou, 510080
Research Site
Guangzhou, 510515
Research Site
Hangzhou, 310020
Research Site
Hangzhou, 310022
Research Site
Harbin, 150081
Research Site
Hefei, 133500
Research Site
Hefei, 230601
Research Site
Linyi, 276000
Research Site
Nanjing, 210029
Research Site
Shandong
Research Site
Shanghai, 200025
Research Site
Shanghai, 200032
Research Site
Shenyang, 110042
Research Site
Shenzhen, 518020
Research Site
Wuhan, 430022
Research Site
Wuhan, 430060
Research Site
Xi'an, 710061
Research Site
Xiamen, 361003
Research Site
Yangzhou, 225001
Research Site
Zhengzhou, 450000

Other trials in China

About this study

Official title: An Open-label, Single-arm, Phase 2 Study to Evaluate the Efficacy and Safety of Trastuzumab Deruxtecan (T-DXd) for Patients With HER2-mutant Metastatic NSCLC Who Have Disease Progression on or After at Least One-line of Treatment (DESTINY-Lung05)

The purpose of this study is to evaluate the efficacy and safety of T-DXd in participants with HER2 mutant metastatic non-squamous NSCLC.

Conditions: HER2-mutant Non-Small Cell Lung Cancer
Being tested: Trastuzumab deruxtecan
Keywords: DL05, T-DXd, HER2-mutant Non-Small Cell Lung Cancer, NSCLC, Trastuzumab deruxtecan, ERBB2

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Trastuzumab deruxtecanDrug
Also called T-DXd, DS-8201a
administered as an IV infusion

Study groups in NCT05246514
Study group	Role	What they receive
T-DXd arm	Experimental	Participants will receive T-DXd as an IV infusion Q3W, on Day 1 of each 3-week cycle. Receives: Drug: Trastuzumab deruxtecan

What is being measured

The primary outcome is the main question the study is designed to answer.

ICR-assessed ORR (Objective Response Rate)
Confirmed ORR, defined as the percentage of participants with confirmed complete response or partial response, as assessed by independent central review(ICR) based on RECIST 1.1.
Measured: Tumour assessments (per RECIST 1.1) every 6 weeks for the first 48 weeks relative to the date of enrolment and then every 9 weeks thereafter. Assessed up to 28 months. (from date of enrolment to final analysis data cut-off)

Secondary outcomes (10)

Investigator-assessed ORR (Objective Response Rate)
Confirmed ORR is defined as the percentage of participants who have a confirmed CR or confirmed PR, as determined by the investigator at local site per RECIST 1.1
Measured: Tumour assessments (per RECIST 1.1) every 6 weeks for the first 48 weeks relative to the date of enrolment and then every 9 weeks thereafter. Assessed up to 28 months. (from date of enrolment to final analysis data cut-off)
ICR-assessed DoR (Duration of Response)
DoR is time from the initial confirmed response (CR or PR) until documented tumour progression or death from any cause.
Measured: Tumour assessments (per RECIST 1.1) every 6 weeks for the first 48 weeks relative to the date of enrolment and then every 9 weeks thereafter. Assessed up to 28 months.
Investigator-assessed DoR (Duration of Response)
DoR is time from the initial confirmed response (CR or PR) until documented tumour progression or death from any cause.
Measured: Tumour assessments (per RECIST 1.1) every 6 weeks for the first 48 weeks relative to the date of enrolment and then every 9 weeks thereafter. Assessed up to 28 months.
ICR-assessed and Investigator-assessed DCR (Disease Control Rate)
DCR is the percentage of participants who achieved confirmed CR, PR, or SD during study intervention.
Measured: Tumour assessments (per RECIST 1.1) every 6 weeks for the first 48 weeks relative to the date of enrolment and then every 9 weeks thereafter. Assessed up to 28 months.
ICR-assessed and Investigator-assessed PFS (Progression-free Survival)
PFS is the time from date of enrolment until first objective radiographic tumour progression or death from any cause.
Measured: Tumour assessments every 6 weeks after enrolment for the first 48 weeks and then every 9 weeks thereafter until date of RECIST 1.1 defined radiological progressive disease or death. Assessed up to 28 months.
OS (Overall Survival)
OS is the time from date of enrolment until death from any cause.
Measured: From date of enrolment until death due to any cause. Assessed up to 28 months.
ICR-assessed CNS-PFS (Central Nervous System Progression-free Survival)
CNS-PFS is the time from date of enrolment until CNS tumour progression per RECIST 1.1 as assessed by ICR or death due to any cause in the absence of CNS progression.
Measured: Tumour assessments every 6 weeks after enrolment for the first 48 weeks and then every 9 weeks thereafter until date of RECIST 1.1 defined CNS tumour progressive disease or death in the absence of CNS progression. Assessed up to 28 months.
Serum Concentrations of T-DXd
Individual patient data and descriptive statistics will be provided for serum concentration data at each time point for T-DXd.
Measured: 24 weeks from day 1 of cycle 1 to cycle 8
Serum Concentrations of Total Anti-HER2 Antibody
Individual patient data and descriptive statistics will be provided for serum concentration data at each time point for total anti-HER2 antibody.
Measured: 24 weeks from day 1 of cycle 1 to cycle 8
Serum Concentrations of DXd
Individual patient data and descriptive statistics will be provided for serum concentration data at each time point for DXd.
Measured: 24 weeks from day 1 of cycle 1 to cycle 8

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

13 Jul 202231 Dec 2026

First posted18 Feb 2022
Study start13 Jul 2022
Primary completion4 Nov 2024
Study completion31 Dec 2026 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for HER2-mutant Non-Small Cell Lung CancerStudies of the same condition, open and under way.
More trials run by AstraZenecaThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 72 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT05246514
Sponsor's protocol ID: D7811C00001
Acronym: DL-05
Status last verified: Jul 2026
First submitted: 11 Feb 2022
Last updated: 18 Aug 2026
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: Yes: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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A Study of BL-M07D1 in Patients With HER2-Overexpressing or HER2-Mutant Locally Advanced or Metastatic Non-Small Cell Lung Cancer
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RecruitingObservational study
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All HER2-mutant Non-Small Cell Lung Cancer trials

Study at a glance

From the registry record, last updated by the sponsor on 18 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: An Open-label, Single-arm, Phase 2 Study to Evaluate the Efficacy and Safety of Trastuzumab Deruxtecan (T-DXd) for Patients With HER2-mutant Metastatic NSCLC Who Have Disease Progression on or After at Least One-line of Treatment (DESTINY-Lung05)
ClinicalTrials.gov ID: NCT05246514
Acronym / sponsor ID: DL-05 / D7811C00001
Conditions: HER2-mutant Non-Small Cell Lung Cancer
Keywords: DL05, T-DXd, HER2-mutant Non-Small Cell Lung Cancer, NSCLC, Trastuzumab deruxtecan, ERBB2
Phase: Phase 2
Study type: Interventional
Recruitment status: Active, not recruiting
Enrolment: 72 participants (actual)
Lead sponsor: AstraZenecaIndustry (pharma, biotech, devices)
Collaborators: Daiichi Sankyo
Study start: 13 Jul 2022 (actual)
Primary completion: 4 Nov 2024 (actual)
Study completion: 31 Dec 2026 (estimated)
First posted: 18 Feb 2022 (actual)
Results: Posted 4 Dec 2024

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

The purpose of this study is to evaluate the efficacy and safety of T-DXd in participants with HER2 mutant metastatic non-squamous NSCLC.

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
T-DXd arm	Experimental	Drug: Trastuzumab deruxtecanParticipants will receive T-DXd as an IV infusion Q3W, on Day 1 of each 3-week cycle.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (6 listed)

Pathologically documented metastatic non-squamous NSCLC.
Has relapsed from or is refractory to at least one-line of anticancer treatment.
Documented HER2 exon 19 or 20 mutation from central FFPE tumour tissue testing.
WHO or ECOG performance status of 0 or 1.
Presence of at least one measurable lesion assessed by the investigator based on RECIST 1.1.

Key exclusion criteria (5 listed)

Mixed small cell lung cancer, squamous histology NSCLC, and sarcomatoid histology variant NSCLC.
Corrected QT interval (QTcF) prolongation to > 470 ms (females) or > 450 ms (males), based on average of the screening triplicate 12-lead ECG.
History of (non-infectious) ILD/pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening.
Has unresolved toxicities from previous anticancer therapy, defined as toxicities (excluding alopecia) not yet resolved to Grade ≤1 or baseline. Participants with clinically stable chronic Grade 2 toxicity not reasonably expected to be exacerbated by study intervention may be included only after consultation with the AstraZeneca study physician or designee.
Has been previously treated with HER2-targeted therapies, except for pan-HER class TKIs or has received prior treatment with an ADC which consists of an exatecan derivative that is a topoisomerase I inhibitor.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Trastuzumab deruxtecanAlso: T-DXd, DS-8201aadministered as an IV infusion	Drug	T-DXd arm

Primary outcome

ICR-assessed ORR (Objective Response Rate)
Time frame: Tumour assessments (per RECIST 1.1) every 6 weeks for the first 48 weeks relative to the date of enrolment and then every 9 weeks thereafter. Assessed up to 28 months. (from date of enrolment to final analysis data cut-off)
Confirmed ORR, defined as the percentage of participants with confirmed complete response or partial response, as assessed by independent central review(ICR) based on RECIST 1.1.

10 secondary outcomes

Investigator-assessed ORR (Objective Response Rate)
Time frame: Tumour assessments (per RECIST 1.1) every 6 weeks for the first 48 weeks relative to the date of enrolment and then every 9 weeks thereafter. Assessed up to 28 months. (from date of enrolment to final analysis data cut-off)
ICR-assessed DoR (Duration of Response)
Time frame: Tumour assessments (per RECIST 1.1) every 6 weeks for the first 48 weeks relative to the date of enrolment and then every 9 weeks thereafter. Assessed up to 28 months.
Investigator-assessed DoR (Duration of Response)
Time frame: Tumour assessments (per RECIST 1.1) every 6 weeks for the first 48 weeks relative to the date of enrolment and then every 9 weeks thereafter. Assessed up to 28 months.
ICR-assessed and Investigator-assessed DCR (Disease Control Rate)
Time frame: Tumour assessments (per RECIST 1.1) every 6 weeks for the first 48 weeks relative to the date of enrolment and then every 9 weeks thereafter. Assessed up to 28 months.
ICR-assessed and Investigator-assessed PFS (Progression-free Survival)
Time frame: Tumour assessments every 6 weeks after enrolment for the first 48 weeks and then every 9 weeks thereafter until date of RECIST 1.1 defined radiological progressive disease or death. Assessed up to 28 months.
OS (Overall Survival)
Time frame: From date of enrolment until death due to any cause. Assessed up to 28 months.
ICR-assessed CNS-PFS (Central Nervous System Progression-free Survival)
Time frame: Tumour assessments every 6 weeks after enrolment for the first 48 weeks and then every 9 weeks thereafter until date of RECIST 1.1 defined CNS tumour progressive disease or death in the absence of CNS progression. Assessed up to 28 months.
Serum Concentrations of T-DXd
Time frame: 24 weeks from day 1 of cycle 1 to cycle 8
Serum Concentrations of Total Anti-HER2 Antibody
Time frame: 24 weeks from day 1 of cycle 1 to cycle 8
Serum Concentrations of DXd
Time frame: 24 weeks from day 1 of cycle 1 to cycle 8

Results and safety

Results posted to the registry on 4 Dec 2024, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
T-DXd Arm	72	29

Primary outcome: ICR-assessed ORR (Objective Response Rate)

Time frame: Tumour assessments (per RECIST 1.1) every 6 weeks for the first 48 weeks relative to the date of enrolment and then every 9 weeks thereafter. Assessed up to 28 months. (from date of enrolment to final analysis data cut-off). Number (95% Confidence Interval). Unit: Percentage of participants

Measure	T-DXd Arm n = 72
Value	56.9 (44.7 to 68.6)

Population analysed: Full analysis set

10 secondary outcomes are reported in the full results.

Adverse events

Time frame: From date of informed consent throughout the treatment period and the safety follow-up period (until 40 (+7) days after the last dose of study treatment).. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
T-DXd	41 of 72 (56.9%)	72 of 72 (100%)	41 of 72

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 18 Aug 2026.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Redacted CSPLink provided by the sponsor.
Redacted SAPLink provided by the sponsor.
Redacted CSR synopsisLink provided by the sponsor.
Redacted CSR synopsis version 2.0Link provided by the sponsor.
Individual participant dataSharing planned: Yes. Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

Related trials for HER2-mutant Non-Small Cell Lung Cancer

Not yet recruitingObservational study
Real-World Outcomes of Sevabertinib in HER2-Mutant Advanced NSCLC: A Bidirectional Cohort Study
HER2-mutant Advanced Non-Small Cell Lung Cancer
RecruitingPhase 1/2
The Evaluation of PC14586 in Patients With Advanced Solid Tumors Harboring a TP53 Y220C Mutation (PYNNACLE)
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RecruitingPhase 1
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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

The record lists no contact. Use the official record to reach the sponsor.

28 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Trastuzumab deruxtecan in people with HER2-mutant Non-Small Cell Lung Cancer, run by AstraZeneca at 28 sites in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 18 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 28 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 4 Dec 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

ICR-assessed ORR (Objective Response Rate) (time frame: Tumour assessments (per RECIST 1.1) every 6 weeks for the first 48 weeks relative to the date of enrolment and then every 9 weeks thereafter. Assessed up to 28 months. (from date of enrolment to final analysis data cut-off)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05246514.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Aug 2026.