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
An Open-label, Randomized, Multicenter, Phase 3 Study to Assess the Efficacy and Safety of Trastuzumab Deruxtecan as First-line Treatment of Unresectable, Locally Advanced, or Metastatic NSCLC Harboring HER2 Exon 19 or 20 Mutations (DESTINY-Lung04)
3 other identifiers
interventional
454
20 countries
130
Brief Summary
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
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3
Started Oct 2021
Longer than P75 for phase_3
130 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
September 9, 2021
CompletedFirst Posted
Study publicly available on registry
September 17, 2021
CompletedStudy Start
First participant enrolled
October 28, 2021
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 30, 2026
CompletedStudy Completion
Last participant's last visit for all outcomes
July 30, 2027
ExpectedDecember 23, 2025
December 1, 2025
4.4 years
September 9, 2021
December 22, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Progression Free Survival (PFS) by Blinded Independent Central Review (BICR)
Defined as time from randomization until progression per RECIST 1.1 as assessed by Blinded Independent Central Review (BICR), or death due to any cause.
Until progression or death, assessed up to approximately 12 months
Secondary Outcomes (15)
Overall Survival (OS)
Until death, assessed up to approximately 28 months.
Progression Free Survival (PFS) by investigator assessment
Until progression, assessed up to approximately 12 months
Objective Response Rate (ORR)
Until progression, assessed up to approximately 12 months
Duration of Response (DoR)
Until progression, assessed up to approximately 12 months
Time to second progression or death (PFS2)
Assessed up to approximately 20 months
- +10 more secondary outcomes
Study Arms (2)
Arm 1
EXPERIMENTALTrastuzumab Deruxtecan (T-DXd)
Arm 2
ACTIVE COMPARATORStandard of Care Treatment (platinum, pemetrexed and pembrolizumab)
Interventions
Trastuzumab Deruxtecan administered by intravenous infusion
Investigator's choice of platinum chemotherapy (cisplatin) administered by intravenous infusion
Investigator's choice of platinum chemotherapy (carboplatin) administered by intravenous infusion
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- AstraZenecalead
- Daiichi Sankyocollaborator
Study Sites (130)
Research Site
Anchorage, Alaska, 99508, United States
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Los Alamitos, California, 90720, United States
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Los Angeles, California, 90048, United States
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Orange, California, 92868, United States
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San Francisco, California, 94143, United States
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Santa Monica, California, 90404, United States
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Silver Spring, Maryland, 20910, United States
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Boston, Massachusetts, 02215, United States
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Ann Arbor, Michigan, 48109, United States
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Basking Ridge, New Jersey, 07920, United States
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Middletown, New Jersey, 07748, United States
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Montvale, New Jersey, 07645, United States
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New Brunswick, New Jersey, 08901, United States
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Commack, New York, 11725, United States
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Harrison, New York, 10604, United States
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New York, New York, 10065, United States
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Uniondale, New York, 11553, United States
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Pittsburgh, Pennsylvania, 15232, United States
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Dallas, Texas, 75246, United States
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Linz, 4020, Austria
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Vienna, 1210, Austria
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Ghent, 9000, Belgium
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Leuven, 3000, Belgium
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Barretos, 14784-400, Brazil
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Blumenau, 89010-340, Brazil
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Brasília, 70200-730, Brazil
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Natal, 59075-740, Brazil
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Salvador, 40170-110, Brazil
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São Paulo, 01321-001, Brazil
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São Paulo, 01327-001, Brazil
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Uberlândia, 38408-150, Brazil
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Vancouver, British Columbia, V5Z 4E6, Canada
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Brampton, Ontario, L6R 3J7, Canada
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Toronto, Ontario, M5G 1Z5, Canada
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Montreal, Quebec, H4A 3J1, Canada
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Beijing, 100142, China
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Beijing, 100730, China
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Changchun, 130021, China
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Changsha, 410008, China
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Changsha, 410013, China
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Chengdu, 610041, China
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Fuzhou, 350014, China
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Guangzhou, 510080, China
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Hangzhou, 310020, China
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Jinan, 250117, China
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Kunming, 650101, China
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Kunming, 650118, China
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Linhai, 317000, China
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Nanchang, 330006, China
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Nanjing, 210029, China
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Shanghai, 200032, China
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Shenyang, 110016, China
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Shenzhen, 518020, China
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Wenzhou, CN-325000, China
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Wuhan, 430022, China
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Xi'an, 710061, China
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Xiamen, 361003, China
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Yangzhou, 225001, China
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Vejle, 7100, Denmark
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Bordeaux, 33000, France
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Dijon, 21079, France
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Le Mans, 72037, France
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Lyon, 69373, France
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Marseille, 13915, France
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Nantes, 44093, France
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Toulouse, 31059, France
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Villejuif, 94805, France
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Cologne, 50937, Germany
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Dresden, 01307, Germany
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Mainz, 55131, Germany
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München, 81377, Germany
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Oldenburg, 26121, Germany
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Hong Kong, HKG, Hong Kong
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Hong Kong, Hong Kong
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Jordan, HKG, Hong Kong
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Bangalore, 560027, India
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Delhi, 110085, India
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Hyderabad, 500032, India
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Mumbai, 400012, India
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Nashik, 422002, India
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Milan, 20141, Italy
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Monza, 20090, Italy
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Orbassano, 10043, Italy
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Parma, 43100, Italy
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Roma, 00168, Italy
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Verona, 37126, Italy
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Chūōku, 104-0045, Japan
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Fukuoka, 812-8582, Japan
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Kashiwa, 277-8577, Japan
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Matsuyama, 791-0280, Japan
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Niigata, 951-8566, Japan
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Okayama, 700-8558, Japan
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Osaka, 541-8567, Japan
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Osakasayama-shi, 589-8511, Japan
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Sapporo, 060-8638, Japan
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Sendai, 980-0873, Japan
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Sunto-gun, 411-8777, Japan
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Yokohama, 241-8515, Japan
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Yonago-shi, 683-8504, Japan
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Mexico City, '14080, Mexico
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Mexico City, 03810, Mexico
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Amsterdam, 1081 HV, Netherlands
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Groningen, 9700 RB, Netherlands
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Nijmegen, 6525 GA, Netherlands
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Gdansk, 80-952, Poland
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Olsztyn, 10-357, Poland
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Przemyśl, 37-700, Poland
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Warsaw, 02-781, Poland
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Cheongju-si, 28644, South Korea
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Goyang-si, 10408, South Korea
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Gyeonggi-do, 13620, South Korea
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Seoul, 03080, South Korea
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Seoul, 05505, South Korea
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Seoul, 06351, South Korea
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L'Hospitalet de Llobregat, 08908, Spain
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Madrid, 28041, Spain
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Málaga, 29730, Spain
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Valencia, 46026, Spain
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Kaohsiung City, 833, Taiwan
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Taichung, 40201, Taiwan
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Taichung, 40705, Taiwan
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Tainan, 70403, Taiwan
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Taipei, 10048, Taiwan
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Taipei, 235, Taiwan
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Taipei, TAIWAN, Taiwan
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Taoyuan District, 333, Taiwan
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Çankaya, 06680, Turkey (Türkiye)
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Edirne, 22030, Turkey (Türkiye)
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Izmir, 35040, Turkey (Türkiye)
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Kadıkoy/Istanbul, 34722, Turkey (Türkiye)
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
September 9, 2021
First Posted
September 17, 2021
Study Start
October 28, 2021
Primary Completion
March 30, 2026
Study Completion (Estimated)
July 30, 2027
Last Updated
December 23, 2025
Record last verified: 2025-12
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP
- 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.
- 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.
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.