A Study to Investigate the Efficacy and Safety of Trastuzumab Deruxtecan as the First Treatment Option for Unresectable, Locally Advanced/Metastatic Non-Small Cell Lung Cancer With HER2 Mutations

NCT ID: NCT05048797

Last Updated: 2025-12-23

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE3

Total Enrollment

454 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-10-28

Study Completion Date

2027-07-30

Brief Summary

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DESTINY-Lung04 will investigate the efficacy and safety of Trastuzumab Deruxtecan (T-DXd) versus Standard of Care (SoC) as first-line treatment of Non-Small Cell Lung Cancer (NSCLC) with HER2 Exon 19 or 20 mutations

Detailed Description

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Eligible participants will be those diagnosed with unresectable, locally advanced or metastatic histologically documented non-squamous NSCLC with HER2 exons 19 or 20 mutations and who are treatment-naïve for palliative intent systemic therapy for locally advanced or metastatic disease.

The study aims to evaluate the efficacy, safety and tolerability of trastuzumab deruxtecan as first-line treatment of Non-Small Cell Lung Cancer (NSCLC) as compared with Standard of Care treatment (Investigator's choice of cisplatin or carboplatin + pembrolizumab + pemetrexed). This study aims to see if trastuzumab deruxtecan allows patients to live longer without the cancer getting worse or simply to live longer, compared to patients receiving standard of care treatment. This study is also looking to see how the treatment and the cancer affects patients' quality of life.

Conditions

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Locally Advanced or Metastatic Non-Small Cell Lung Cancer

Keywords

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DS-8201a HER2 exon 19 or 20 mutations ERBB2 gene (coding for the HER2 protein) T-DXd Trastuzumab Deruxtecan Locally advanced and unresectable non-squamous NSCLC Metastatic non-squamous NSCLC Non-small cell lung cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

This study consists of two open-label treatment arms:

Arm 1: Trastuzumab Deruxtecan Arm 2: Standard of Care treatment (platinum, pemetrexed and pembrolizumab)
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Arm 1

Trastuzumab Deruxtecan (T-DXd)

Group Type EXPERIMENTAL

Trastuzumab Deruxtecan

Intervention Type DRUG

Trastuzumab Deruxtecan administered by intravenous infusion

Arm 2

Standard of Care Treatment (platinum, pemetrexed and pembrolizumab)

Group Type ACTIVE_COMPARATOR

Cisplatin

Intervention Type DRUG

Investigator's choice of platinum chemotherapy (cisplatin) administered by intravenous infusion

Carboplatin

Intervention Type DRUG

Investigator's choice of platinum chemotherapy (carboplatin) administered by intravenous infusion

Pembrolizumab

Intervention Type DRUG

Pembrolizumab administered by intravenous infusion

Pemetrexed

Intervention Type DRUG

Pemetrexed administered by intravenous infusion

Interventions

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Trastuzumab Deruxtecan

Trastuzumab Deruxtecan administered by intravenous infusion

Intervention Type DRUG

Cisplatin

Investigator's choice of platinum chemotherapy (cisplatin) administered by intravenous infusion

Intervention Type DRUG

Carboplatin

Investigator's choice of platinum chemotherapy (carboplatin) administered by intravenous infusion

Intervention Type DRUG

Pembrolizumab

Pembrolizumab administered by intravenous infusion

Intervention Type DRUG

Pemetrexed

Pemetrexed administered by intravenous infusion

Intervention Type DRUG

Other Intervention Names

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DS-8201a; T-DXd

Eligibility Criteria

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Inclusion Criteria

* Participants at least 18 years of age
* Locally advanced and unresectable NSCLC, not amenable to curative therapy, or metastatic disease
* Histologically documented non-squamous NSCLC with HER2 mutation in exons 19 or 20 by tissue NGS or ctDNA
* Treatment-naïve for palliative intent systemic therapy for locally advanced or metastatic disease
* Left ventricular ejection fraction (LVEF) ≥ 50%
* Measurable disease assessed by Investigator based on RECIST 1.1
* Protocol-defined adequate organ function including cardiac, renal, hepatic function
* ECOG 0-1
* Having tumour tissue available for central testing

Exclusion Criteria

* Tumors with targetable alterations to EGFR (or other targetable mutations including but not limited to ALK, if routinely tested as a targetable alteration with approved available therapy)
* Any untreated brain metastases, including asymptomatic or clinically inactive brain metastases
* Active autoimmune or inflammatory disorders
* Medical history of myocardial infarction within 6 months prior to randomization
* History of non-infectious pneumonitis/ILD, current or suspected ILD
* Lung-specific intercurrent clinical significant severe illness
* Contraindication to platinum-based doublet chemotherapy or pembrolizumab
Minimum Eligible Age

18 Years

Maximum Eligible Age

123 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Daiichi Sankyo

INDUSTRY

Sponsor Role collaborator

AstraZeneca

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Research Site

Anchorage, Alaska, United States

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Los Alamitos, California, United States

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Los Angeles, California, United States

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Orange, California, United States

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San Francisco, California, United States

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Santa Monica, California, United States

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Silver Spring, Maryland, United States

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Boston, Massachusetts, United States

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Ann Arbor, Michigan, United States

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Basking Ridge, New Jersey, United States

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Middletown, New Jersey, United States

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Montvale, New Jersey, United States

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New Brunswick, New Jersey, United States

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Commack, New York, United States

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Harrison, New York, United States

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New York, New York, United States

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Uniondale, New York, United States

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Pittsburgh, Pennsylvania, United States

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Dallas, Texas, United States

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Linz, , Austria

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Vienna, , Austria

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Ghent, , Belgium

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Leuven, , Belgium

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Barretos, , Brazil

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Blumenau, , Brazil

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Brasília, , Brazil

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Natal, , Brazil

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Salvador, , Brazil

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São Paulo, , Brazil

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São Paulo, , Brazil

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Uberlândia, , Brazil

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Vancouver, British Columbia, Canada

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Brampton, Ontario, Canada

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Toronto, Ontario, Canada

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Montreal, Quebec, Canada

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Beijing, , China

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Beijing, , China

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Changchun, , China

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Changsha, , China

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Changsha, , China

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Chengdu, , China

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Fuzhou, , China

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Guangzhou, , China

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Hangzhou, , China

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Jinan, , China

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Kunming, , China

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Kunming, , China

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Linhai, , China

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Nanchang, , China

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Nanjing, , China

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Shanghai, , China

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Shenyang, , China

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Shenzhen, , China

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Wenzhou, , China

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Wuhan, , China

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Xi'an, , China

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Xiamen, , China

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Yangzhou, , China

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Vejle, , Denmark

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Bordeaux, , France

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Dijon, , France

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Le Mans, , France

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Lyon, , France

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Marseille, , France

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Nantes, , France

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Toulouse, , France

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Villejuif, , France

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Cologne, , Germany

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Dresden, , Germany

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Mainz, , Germany

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München, , Germany

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Oldenburg, , Germany

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Hong Kong, , Hong Kong

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Hong Kong, , Hong Kong

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Jordan, , Hong Kong

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Bangalore, , India

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Delhi, , India

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Hyderabad, , India

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Mumbai, , India

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Nashik, , India

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Milan, , Italy

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Monza, , Italy

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Orbassano, , Italy

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Parma, , Italy

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Roma, , Italy

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Verona, , Italy

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Chūōku, , Japan

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Fukuoka, , Japan

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Kashiwa, , Japan

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Matsuyama, , Japan

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Niigata, , Japan

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Okayama, , Japan

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Osaka, , Japan

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Osakasayama-shi, , Japan

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Sapporo, , Japan

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Sendai, , Japan

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Sunto-gun, , Japan

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Yokohama, , Japan

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Yonago-shi, , Japan

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Mexico City, , Mexico

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Mexico City, , Mexico

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Amsterdam, , Netherlands

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Groningen, , Netherlands

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Nijmegen, , Netherlands

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Gdansk, , Poland

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Olsztyn, , Poland

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Przemyśl, , Poland

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Warsaw, , Poland

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Cheongju-si, , South Korea

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Goyang-si, , South Korea

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Gyeonggi-do, , South Korea

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Seoul, , South Korea

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Seoul, , South Korea

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Seoul, , South Korea

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L'Hospitalet de Llobregat, , Spain

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Madrid, , Spain

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Málaga, , Spain

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Valencia, , Spain

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Kaohsiung City, , Taiwan

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Taichung, , Taiwan

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Taichung, , Taiwan

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Tainan, , Taiwan

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Taipei, , Taiwan

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Taipei, , Taiwan

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Taipei, , Taiwan

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Taoyuan District, , Taiwan

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Çankaya, , Turkey (Türkiye)

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Edirne, , Turkey (Türkiye)

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Izmir, , Turkey (Türkiye)

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Kadıkoy/Istanbul, , Turkey (Türkiye)

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Countries

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Sweden United States Austria Belgium Brazil Canada China Denmark France Germany Hong Kong India Italy Japan Mexico Netherlands Poland South Korea Spain Taiwan Turkey (Türkiye)

Related Links

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https://www.lungcancerstudylocator.com/trial/listing/304247

Lung Cancer Study Locator details (for US)

Other Identifiers

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2021-000634-33

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

2023-503674-20-00

Identifier Type: REGISTRY

Identifier Source: secondary_id

D967SC00001

Identifier Type: -

Identifier Source: org_study_id