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

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: Active, not recruiting
• Conditions: HER2-mutant Non-Small Cell Lung Cancer
• Intervention / Treatment: Drug: Trastuzumab deruxtecan

• Study Type: Interventional
• Enrollment (Actual): 72
• Phase: Phase 2

Contacts and Locations

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

Eligibility Criteria

• 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

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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

Outcome Measure	Measure Description	Time Frame
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.	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

Outcome Measure	Measure Description	Time Frame
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	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.	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.	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.	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.	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.	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.	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.	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.	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.	24 weeks from day 1 of cycle 1 to cycle 8

Collaborators and Investigators

• Sponsor: AstraZeneca
• Collaborators: Daiichi Sankyo

Publications and helpful links

Helpful Links

• Redacted CSP
• Redacted SAP
• Redacted CSR synopsis
• Redacted CSR synopsis version 2.0

Study record dates

Study Major Dates

• Study Start (Actual): July 13, 2022
• Primary Completion (Actual): November 4, 2024
• Study Completion (Estimated): June 30, 2026

Study Registration Dates

• First Submitted: February 11, 2022
• First Submitted That Met QC Criteria: February 11, 2022
• First Posted (Actual): February 18, 2022

Study Record Updates

• Last Update Posted (Actual): May 12, 2026
• Last Update Submitted That Met QC Criteria: April 21, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: NSCLC; T-DXd; Trastuzumab deruxtecan; ERBB2; DL05; HER2-mutant Non-Small Cell Lung Cancer
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Carcinoma, Non-Small-Cell Lung; Antineoplastic Agents, Immunological; Antineoplastic Agents; Immunologic Factors; Physiological Effects of Drugs; Immunoconjugates; trastuzumab deruxtecan
• Other Study ID 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