Locally Advanced or Metastatic Non-Small Cell Lung CancerPhase 3NCT05048797
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
A Phase 3 study testing Trastuzumab Deruxtecan, Cisplatin and Carboplatin in people with Locally Advanced or Metastatic Non-Small Cell Lung Cancer, run by AstraZeneca at 130 sites in 20 countries.
Trial 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 Read more about this study
- Who is it for?
- Ages 18 to 123 years
- Conditions the study is for
- Locally Advanced or Metastatic Non-Small Cell Lung Cancer
- What is being tested?
- Trastuzumab Deruxtecan, Cisplatin and Carboplatin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 454 participants
- Where
- 130 sitesin 20 countries
- Study dates
- 28 Oct 2021to 30 Jul 2027
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 123 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- Protocol-defined adequate organ function including cardiac, renal, hepatic function
- ECOG 0-1
- Having tumour tissue available for central testing
Who cannot join
- 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
Trial locations and contacts
130 sites in 20 countries.
130 sites in 20 countries
China23 sites
Research Site
Beijing, 100142
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Beijing, 100730
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Changchun, 130021
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Changsha, 410008
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Changsha, 410013
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Chengdu, 611135
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Fuzhou, 350014
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Guangzhou, 510080
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Hangzhou, 310020
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Jinan, 250117
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Kunming, 650101
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Kunming, 650118
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Linhai, 317000
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Nanchang, 330006
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Nanjing, 210029
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Shanghai, 200032
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Shenyang, 110016
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Shenzhen, 518020
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Wenzhou, CN-325000
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Wuhan, 430022
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Xi'an, 710061
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Xiamen, 361003
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Yangzhou, 225001
United States19 sites
Research Site
Anchorage, Alaska, 99508
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Ann Arbor, Michigan, 48109
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Basking Ridge, New Jersey, 07920
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Boston, Massachusetts, 02215
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Commack, New York, 11725
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Dallas, Texas, 75246
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Harrison, New York, 10604
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Los Alamitos, California, 90720
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Los Angeles, California, 90048
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Middletown, New Jersey, 07748
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Montvale, New Jersey, 07645
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New Brunswick, New Jersey, 08901
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New York, New York, 10065
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Orange, California, 92868
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Pittsburgh, Pennsylvania, 15232
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San Francisco, California, 94143
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Santa Monica, California, 90404
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Silver Spring, Maryland, 20910
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Uniondale, New York, 11553
Japan13 sites
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Chūōku, 104-0045
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Fukuoka, 812-8582
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Kashiwa, 277-8577
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Matsuyama, 791-0280
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Niigata, 951-8566
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Okayama, 700-8558
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Osaka, 541-8567
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Sakai, 590-0197
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Sapporo, 060-8638
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Sendai, 981-0914
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Sunto-gun, 411-8777
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Yokohama, 241-8515
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Yonago-shi, 683-8504
Brazil8 sites
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Barretos, 14784-400
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Blumenau, 89010-340
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Brasília, 70200-730
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Natal, 59075-740
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Salvador, 40170-110
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São Paulo, 01321-001
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São Paulo, 01327-001
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Uberlândia, 38408-150
France8 sites
Research Site
Bordeaux, 33000
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Dijon, 21079
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Le Mans, 72037
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Lyon, 69373
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Marseille, 13915
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Nantes, 44093
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Toulouse, 31059
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Villejuif, 94805
Taiwan8 sites
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Kaohsiung City, 833
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Taichung, 40201
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Taichung, 40705
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Tainan, 70403
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Taipei, 10048
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Taipei, 235
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Taipei, TAIWAN
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Taoyuan, 333
Italy6 sites
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Milan, 20141
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Monza, 20090
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Orbassano, 10043
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Parma, 43126
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Roma, 00168
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Verona, 37134
South Korea6 sites
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Cheongju-si, 28644
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Goyang-si, 10408
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Gyeonggi-do, 13620
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Seoul, 03080
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Seoul, 05505
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Seoul, 06351
Germany5 sites
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Cologne, 50937
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Dresden, 01307
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Mainz, 55131
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München, 81377
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Oldenburg, 26121
India5 sites
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Bangalore, 560027
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Delhi, 110085
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Hyderabad, 500032
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Mumbai, 400012
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Nashik, 422002
Canada4 sites
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Brampton, Ontario, L6R 3J7
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Montreal, Quebec, H4A 3J1
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Toronto, Ontario, M5G 1Z5
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Vancouver, British Columbia, V5Z 4E6
Poland4 sites
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Gdansk, 80-952
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Olsztyn, 10-357
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Przemyśl, 37-700
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Warsaw, 02-781
Spain4 sites
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L'Hospitalet de Llobregat, 08908
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Madrid, 28041
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Málaga, 29730
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Valencia, 46026
Turkey (Türkiye)4 sites
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Çankaya, 06680
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Edirne, 22030
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Izmir, 35040
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Kadıkoy/Istanbul, 34722
Hong Kong3 sites
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Hong Kong, 999077
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Hong Kong
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Jordan, 999077
Netherlands3 sites
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Amsterdam, 1081 HV
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Groningen, 9700 RB
Research Site
Nijmegen, 6525 GA
Mexico2 sites
Research Site
Mexico City, '14080
Research Site
Mexico City, 03810
About this study
Official title: 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)
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
Read the detailed description
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.
- Being tested
- Trastuzumab Deruxtecan, Cisplatin, Carboplatin, Pembrolizumab, Pemetrexed
- Keywords
- 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
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Trastuzumab DeruxtecanDrug
Also called DS-8201a; T-DXd
Trastuzumab Deruxtecan administered by intravenous infusion
CisplatinDrug
Investigator's choice of platinum chemotherapy (cisplatin) administered by intravenous infusion
CarboplatinDrug
Investigator's choice of platinum chemotherapy (carboplatin) administered by intravenous infusion
PembrolizumabDrug
Pembrolizumab administered by intravenous infusion
PemetrexedDrug
Pemetrexed administered by intravenous infusion
| Study group | Role | What they receive |
|---|---|---|
| Arm 1 | Experimental | Trastuzumab Deruxtecan (T-DXd) Receives: Drug: Trastuzumab Deruxtecan |
| Arm 2 | Active comparator | Standard of Care Treatment (platinum, pemetrexed and pembrolizumab) Receives: Drug: Cisplatin; Drug: Carboplatin; Drug: Pembrolizumab; Drug: Pemetrexed |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Until progression or death, assessed up to approximately 12 months
Secondary outcomes (15)
Overall Survival (OS)
Defined as time from randomization until the date of death due to any cause.
Measured: Until death, assessed up to approximately 28 months.
Progression Free Survival (PFS) by investigator assessment
Defined as time from randomization until progression per RECIST 1.1 as assessed by the investigator, or death due to any cause.
Measured: Until progression, assessed up to approximately 12 months
Objective Response Rate (ORR)
Defined as the proportion of participants who have a complete response (CR) or partial response (PR) as assessed by Blinded Independent Central Review (BICR) and investigator according to RECIST 1.1
Measured: Until progression, assessed up to approximately 12 months
Duration of Response (DoR)
Defined as the time from the date of first documented response until date of documented progression as assessed by Blinded Independent Central Review (BICR) and investigator assessment according to RECIST 1.1.
Measured: Until progression, assessed up to approximately 12 months
Time to second progression or death (PFS2)
Defined as the time from randomization until second progression on next-line of treatment as assessed by investigator at the local site using assessments conducted per local standard clinical practice, or death due to any cause.
Measured: Assessed up to approximately 20 months
Landmark analysis of PFS (PFS12)
Defined as proportion of participants alive and progression-free at 12 months, as assessed by Blinded Independent Central Review (BICR) and investigator.
Measured: Assessed up to approximately 12 months
Landmark analysis of OS (OS24)
Defined as proportion of participants alive at 24 months
Measured: Assessed up to approximately 24 months
Central Nervous System (CNS) - Progression Free Survival (PFS)
Defined as time from randomization until Central Nervous System (CNS) progression per RECIST 1.1 as assessed by Blinded Independent Central Review (BICR) or death due to any cause in the absence of CNS progression.
Measured: Until CNS progression or death, assessed up to approximately 12 months
Safety and tolerability of T-DXd versus Standard of Care treatment
Assessed by the occurrence of AEs, SAEs, and changes from baseline in laboratory parameters, vital signs, ECG, and ECHO/MUGA scan results.
Measured: Until progression or death, assessed up to approximately 28 months
Pharmacokinetics (PK) of T-DXd, total anti-HER2 antibody and DXd in serum
Serum concentration of T-DXd, total anti-HER2 antibody and DXd.
Measured: Up to cycle 4, approximately 12 weeks
Immunogenicity of T-DXd
Presence of anti-drug antibodies (ADAs) for T-DXd.
Measured: Until progression, assessed up to approximately 13 months
Patient-reported pulmonary symptoms associated with Non-Small Cell Lung Cancer
Time to sustained deterioration in pulmonary symptoms (cough, dyspnea, chest pain) while on treatment using the Non-Small Cell Lung Cancer-Symptom Assessment Questionnaire (NSCLC-SAQ).
Measured: Until progression, assessed up to approximately 13 months
Patient-reported tolerability of T-DXd described using symptomatic AEs
Symptomatic AEs: Descriptive summary of the proportion of participants reporting symptomatic AEs while on treatment, as assessed by the Patient-reported outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) and items from the European Organisation for Research and Treatment of Cancer (EORTC) Item Library.
Measured: Until progression, assessed up to approximately 13 months
Patient-reported tolerability of T-DXd described using overall side-effect bother
Overall side-effect bother: Descriptive summary of the proportion of participants reporting overall side-effect bother on the Patient's Global Impression of Treatment Tolerability (PGI-TT) while on treatment.
Measured: Until progression, assessed up to approximately 13 months
Patient-reported tolerability of T-DXd described using physical function
Physical Function: The proportion of participants with maintained or improved physical function while on treatment, based on the European Organisation for Research and Treatment of Cancer 30-item core quality of life questionnaire (EORTC-QLQ-C30) physical functioning scale.
Measured: Until progression, assessed up to approximately 13 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Sep 2021
- Study start28 Oct 2021
- Primary completion9 Jun 2026
- Study completion30 Jul 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Locally Advanced or Metastatic Non-Small Cell Lung CancerStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- This study consists of two open-label treatment arms: Arm 1: Trastuzumab Deruxtecan Arm 2: Standard of Care treatment (platinum, pemetrexed and pembrolizumab)
- Masking
- None (open label)
- Enrolment
- 454 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Daiichi Sankyo
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05048797
- Sponsor's protocol ID
- D967SC00001
- Other IDs
- 2023-503674-20-00, 2021-000634-33, 2023
- Status last verified
- Oct 2026
- First submitted
- 9 Sep 2021
- Last updated
- 21 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.