A Single Arm Phase 2 Study to Evaluate Efficacy and Safety of Trastuzumab Deruxtecan for Patients With HER2 Mutant NSCLC (DL-05)

July 24, 2026 updated by: AstraZeneca

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Active, not recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
72

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: T-DXd arm
Participants will receive T-DXd as an IV infusion Q3W, on Day 1 of each 3-week cycle.
Drug: Trastuzumab deruxtecan
administered as an IV infusion
Other Names:
  • T-DXd, DS-8201a

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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.
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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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)
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
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.
DoR is time from the initial confirmed response (CR or PR) until documented tumour progression or death from any cause.
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.
DoR is time from the initial confirmed response (CR or PR) until documented tumour progression or death from any cause.
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.
DCR is the percentage of participants who achieved confirmed CR, PR, or SD during study intervention.
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.
PFS is the time from date of enrolment until first objective radiographic tumour progression or death from any cause.
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.
OS is the time from date of enrolment until death from any cause.
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.
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.
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
Individual patient data and descriptive statistics will be provided for serum concentration data at each time point for T-DXd.
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
Individual patient data and descriptive statistics will be provided for serum concentration data at each time point for total anti-HER2 antibody.
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
Individual patient data and descriptive statistics will be provided for serum concentration data at each time point for DXd.
24 weeks from day 1 of cycle 1 to cycle 8

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
AstraZeneca

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Daiichi Sankyo

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
July 13, 2022

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
November 4, 2024

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 31, 2026

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
February 11, 2022

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 11, 2022

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
February 18, 2022

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 18, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 24, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
July 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • D7811C00001

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

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.

IPD Sharing Time Frame

AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

IPD Sharing Access Criteria

When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool. Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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