Phase Ib Study of the Safety of T-DXd and Immunotherapy Agents With and Without Chemotherapy in Advanced or Metastatic HER2+, Non-squamous NSCLC
DL03
A Phase Ib Multicenter, Open-label Study to Evaluate the Safety and Tolerability of Trastuzumab Deruxtecan (T-DXd) and Immunotherapy Agents With and Without Chemotherapy Agents in First-line Treatment of Patients With Advanced or Metastatic Non-squamous Non-small Cell Lung Cancer (NSCLC) and Human Epidermal Growth Factor Receptor 2 (HER2) Overexpression (OE) (DESTINY-Lung03)
3 other identifiers
interventional
304
19 countries
91
Brief Summary
DESTINY-Lung03 will investigate the safety and tolerability of trastuzumab deruxtecan in combination with Immunotherapy Agents with and without chemotherapy in patients with HER2 over-expressing non-small cell lung cancer. The efficacy will be also analyzed as a secondary endpoint.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Mar 2021
Longer than P75 for phase_1
91 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
December 8, 2020
CompletedFirst Posted
Study publicly available on registry
December 28, 2020
CompletedStudy Start
First participant enrolled
March 9, 2021
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 30, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
June 30, 2027
April 13, 2026
February 1, 2026
6.3 years
December 8, 2020
April 8, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Frequency of AEs and SAEs
Occurrence of AEs and SAEs graded according to NCI CTCAE v5.0
Safety and tolerability (and to determine RP2D) will be assessed for approximately 20 months from informed consent
Secondary Outcomes (10)
Confirmed Objective Response Rate (ORR)
An average of approximately 12 months
Duration of Response (DoR)
An average of approximately 20 months
Disease Control Rate (DCR)
An average of approximately 12 months
Progression-free survival (PFS)
An average of approximately 20 months
Overall survival (OS)
An average of approximately 20 months
- +5 more secondary outcomes
Study Arms (10)
Arm 1A: T-DXd, Durvalumab and Cisplatin
EXPERIMENTALT-DXd, Durvalumab and Cisplatin
Arm 1B: T-DXd, Durvalumab and Carboplatin
EXPERIMENTALT-DXd, Durvalumab and Carboplatin
Arm 1C: T-DXd, Durvalumab and Pemetrexed
EXPERIMENTALT-DXd, Durvalumab and Pemetrexed (Arm not initiated)
Arm 1D: T-DXd
EXPERIMENTALT-DXd
Arm 3A: T-DXd and Volrustomig
EXPERIMENTALDrug: T-DXd and Volrustomig T-DXd: administered as an IV infusion Other Name: DS-8201a, Trastuzumab deruxtecan Biological/Vaccine: Volrustomig Volrustomig: administered as an IV infusion Other Name: Volrustomig
Arm 3B: T-DXd, Volrustomig and Carboplatin
EXPERIMENTALDrug: T-DXd, Volrustomig and Carboplatin T-DXd: administered as an IV infusion Other Name: DS-8201a, Trastuzumab deruxtecan Biological/Vaccine: Volrustomig Volrustomig: administered as an IV infusion Other Name: Volrustomig Drug: Carboplatin Carboplatin: administered as an IV infusion
Arm 4A: T-DXd and Rilvegostomig
EXPERIMENTALT-DXd and Rilvegostomig Drug: T-DXd, Rilvegostomig T-DXd: administered as an IV infusion Other Name: DS-8201a, Trastuzumab deruxtecan Biological/Vaccine: Rilvegostomig Rilvegostomig: administered as an IV infusion Other Name: Rilvegostomig, AZD2936
Arm 4B T-DXd and Rilvegostomig with Carboplatin
EXPERIMENTALDrug: T-DXd, Rilvegostomig and Carboplatin T-DXd: administered as an IV infusion Other Name: DS-8201a, Trastuzumab deruxtecan Biological/Vaccine: Rilvegostomig Rilvegostomig: administered as an IV infusion Other Name: Rilvegostomig, AZD2936 Drug: Carboplatin Carboplatin: administered as an IV infusion
Arm 5A: T-DXd and Volrustomig
EXPERIMENTALDrug: T-DXd and volrustomig T-DXd: administered as an IV infusion Other Name: DS-8201a, trastuzumab deruxtecan Biological/Vaccine: Volrustomig Volrustomig: administered as an IV infusion (priming dose in first cycle, fixed dose in subsequent cycles) Other Name: volrustomig
Arm 5B: T-DXd and Volrustomig
EXPERIMENTALDrug: T-DXd and volrustomig T-DXd: administered as an IV infusion Other Name: DS-8201a, trastuzumab deruxtecan Biological/Vaccine: Volrustomig Volrustomig: administered as an IV infusion (fixed dose from first cycle onward) Other Name: volrustomig
Interventions
Carboplatin: administered as an IV infusion
Pemetrexed: administered as an IV infusion (drug not used)
Volrustomig: administered as an IV infusion
Rilvegostomig: administered as an IV infusion
T-DXd: administered as an IV infusion
Durvalumab: administered as an IV infusion
Eligibility Criteria
You may qualify if:
- Histologically documented unresectable locally advanced/metastatic non-squamous NSCLC
- Part 1: Progression after 1 or 2 lines of systemic therapy for recurrent or metastatic setting.
- Part 3, Part 4 and Part 5: Patients must have tumors that do not harbor known genomic alterations or actionable driver kinases, for which approved therapies are available are allowed.
- Part 3, Part 4 and Part 5: Patient must be treatment-naïve for advanced or metastatic NSCLC. Patients who have received prior adjuvant, or neoadjuvant chemotherapy, or definitive chemoradiation for advanced disease are eligible, provided that progression has occurred \> 6 months from end of last therapy
- HER2overexpression status as determined by central review of tumor tissue
- WHO / ECOG performance status of 0 or 1
- Measurable target disease assessed by the investigator using RECIST 1.1
- Has protocol defined adequate organ and bone marrow function
- Part 3, Part 4 and Part 5: Minimum body weight of 35 kg.
You may not qualify if:
- HER2 mutation if previously known
- Has a 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
- Lung-specific intercurrent clinically significant illnesses including, but not limited to, any underlying pulmonary disorder and prior pneumonectomy
- Active primary immunodeficiency known HIV infection, or active chronic and resolved hepatitis B (positive hepatitis B virus surface antigen \[HBsAg+ve\] or hepatitis B virus core antibody (anti-HBc +ve) regardless of HBV DNA level)) or hepatitis C infection. Patients positive for HCV antibody are eligible only if polymerase chain reaction is negative for HCV RNA. Patients should be tested for HIV prior to treatment assignment if required by local regulations or IRB/EC
- Active infection including tuberculosis and uncontrolled infection requiring IV antibiotics, antivirals, or antifungals
- Spinal cord compression or clinically active central nervous system metastases, defined as untreated and symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms
- Medical history of myocardial infarction within 6 months before treatment assignment, symptomatic CHF (New York Heart Association Class II to IV), clinically important cardiac arrhythmias, or a recent (\< 6 months) cardiovascular event including stroke
- For Part 3, Part 4 and Part 5: Cardiomyopathy of any etiology, symptomatic CHF (as defined by New York Heart Association Class \> II), unstable angina pectoris, history of MI within the past 12 months, or cardiac arrhythmia are to be excluded. Patients with troponin levels above ULN at screening (as defined by the manufacturer), and without any myocardial related symptoms, should have a cardiologic consultation before treatment assignment to rule out acute cardiopulmonary events.
- Ascites or pericardial effusion that requires drainage, peritoneal shunt, Pleuroperitoneal shunt or CART (Concentrated Ascites Reinfusion Therapy)
- For Part 3, Part 4 and Part 5: Active non-infectious skin disease (including any grade rash, urticarial, dermatitis, ulceration, or psoriasis) requiring systemic treatment, active or prior documented autoimmune or inflammatory disorders requiring chronic treatment with steroids or other immunosuppressive treatment.
- Unresolved toxicities not yet resolved to Grade ≤ 1 or baseline from previous anticancer therapy OR prior discontinuation of any planned study therapy due to toxicity.
- must not have any medical contraindication to platinum-based chemotherapy.
- Part 3, Part 4 and Part 5 patients must not have had prior exposure to anti-PD-1, anti-PD-L1, anti-CTLA-4, anti-TIGIT or any other experimental immunotherapy in any setting.
- For Part 3, Part 4 and Part 5: History of substance abuse or any other medical or psychological conditions that may, in the opinion of the Investigator, interfere with the subject's participation in the clinical study or evaluation of the clinical study results
- For Part 3, Part 4 and Part 5: History of thromboembolic events within 3 months before the first dose of IP (limited to pulmonary embolism, deep vein thrombosis, or cerebral venous sinus thrombosis).
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- AstraZenecalead
- Daiichi Sankyocollaborator
Study Sites (91)
Research Site
Duarte, California, 91010, United States
Research Site
Newport Beach, California, 92663, United States
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Orange, California, 92868, United States
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Santa Rosa, California, 95403, United States
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Westwood, Kansas, 66205, United States
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Baltimore, Maryland, 21287, United States
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Detroit, Michigan, 48201, United States
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Buffalo, New York, 14263, United States
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New York, New York, 10029, United States
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The Bronx, New York, 10461, United States
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Houston, Texas, 77030, United States
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Fairfax, Virginia, 22031, United States
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Tacoma, Washington, 98405, United States
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Adelaide, 5000, Australia
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Heidelberg, 3084, Australia
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Nedlands, 6009, Australia
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Edegem, 2650, Belgium
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Barretos, 14784-400, Brazil
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Porto Alegre, 90035-903, Brazil
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São Paulo, 05652-900, Brazil
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Winnipeg, Manitoba, R3E 0V9, Canada
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London, Ontario, N6A 5W9, Canada
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Montreal, Quebec, H3T 1E2, Canada
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Changchun, 130000, China
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Chengdu, 610041, China
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Fuzhou, 350011, China
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Shandong, China
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Shanghai, 200433, China
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Zhengzhou, 450000, China
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Bordeaux, 33075, France
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Dijon, 21079, France
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Pierre-Bénite, 69495, France
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Saint-Herblain, 44800, France
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Villejuif, 94805, France
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Kfar Saba, 4428164, Israel
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Tel Litwinsky, 52620, Israel
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Milan, 20133, Italy
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Milan, 20162, Italy
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Monza, 20052, Italy
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Naples, 80131, Italy
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Padova, 35128, Italy
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George Town, 10450, Malaysia
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Kuala Lumpur, 59100, Malaysia
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Kuala Selangor, 62250, Malaysia
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Kuching, 93586, Malaysia
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Amsterdam, 1066 CX, Netherlands
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Bacolod, 6100, Philippines
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Cebu City, 6000, Philippines
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City of Taguig, 1634, Philippines
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Davao City, PH-8000, Philippines
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Manila, 1000, Philippines
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Manila, 1015, Philippines
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Quezon City, 1100, Philippines
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Quezon City, 1112, Philippines
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San Juan City, 1500, Philippines
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Gdansk, 80-214, Poland
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Krakow, 30-727, Poland
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Olsztyn, 10-357, Poland
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Tomaszów Mazowiecki, 97-200, Poland
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Warsaw, 02-781, Poland
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Singapore, 119228, Singapore
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Singapore, 168583, Singapore
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Singapore, 308433, Singapore
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Cheongju-si, 28644, South Korea
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Goyang-si, 10408, South Korea
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Jinju, 52727, South Korea
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Seoul, 03722, South Korea
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Seoul, 05505, South Korea
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Seoul, 06351, South Korea
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Badalona, 08013, Spain
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Madrid, 28041, Spain
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Seville, 41013, Spain
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Valencia, 46010, Spain
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Kaohsiung City, 833, Taiwan
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Taichung, 402, Taiwan
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Taichung, 40705, Taiwan
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Tainan, 70403, Taiwan
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Taipei, 100, Taiwan
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Taipei, 11217, Taiwan
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Taipei, 235, Taiwan
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Taoyuan District, 333, Taiwan
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Bangkok, 10300, Thailand
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Bangkok, 10330, Thailand
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Hat Yai, 90110, Thailand
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Khon Kaen, 40002, Thailand
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Muang, 22000, Thailand
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Muang, 50200, Thailand
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Ankara, 06800, Turkey (Türkiye)
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Ankara, 6200, Turkey (Türkiye)
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Bornova-Izmir, 35100, Turkey (Türkiye)
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Istanbul, 31755, Turkey (Türkiye)
Related Publications (1)
Planchard D, Kim HR, Suksombooncharoen T, Li R, Cortinovis D, Han JY, Samol J, Runglodvatana Y, Lee KY, Chang GC, Lee CH, Kowalski D, Saw SPL, Huang Y, Ruiter G, Ahn MJ, Yang TY, Yang CT, Sookprasert A, Nakajima EC, Alfon J, McEwen R, Chang YT, Yang JC. Trastuzumab Deruxtecan in Patients With HER2-Overexpressing NSCLC: Results From Part 1 of the Open-Label, Multicenter, Phase 1b DESTINY-Lung03 Trial. J Thorac Oncol. 2025 Dec 23:103541. doi: 10.1016/j.jtho.2025.12.080. Online ahead of print.
PMID: 41448488DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Central Study Contacts
AstraZeneca Clinical Study Information Center
CONTACT
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
December 8, 2020
First Posted
December 28, 2020
Study Start
March 9, 2021
Primary Completion (Estimated)
June 30, 2027
Study Completion (Estimated)
June 30, 2027
Last Updated
April 13, 2026
Record last verified: 2026-02
Data Sharing
- IPD Sharing
- Will share
- 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. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.