Skip to main content
OpenTrials
Active, Not Recruiting

NCT Number: NCT05246514

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

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

Active, Not Recruiting

This study is active but is not currently recruiting participants.

Notify Me

Key information

Conditions

HER2-mutant Non-Small Cell Lung Cancer

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Research Site, Baoding, China

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Trastuzumab Deruxtecan

Drug

administered as an IV infusion

Other names: T-DXd, DS-8201a

Primary outcomes

  1. 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.

Secondary outcomes

  1. 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

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

Sponsors and collaborators

Lead sponsor

AstraZeneca

Industry

Collaborators

  • Daiichi Sankyo

Registry information

Official study 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)

Acronym: DL-05

Important dates

Study start
2022
Primary completion
2024
Study completion
2026
First posted
Feb 18, 2022
Registry last updated
May 12, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.