Tests trastuzumab deruxtecan with immunotherapy for HER2-positive lung cancer
Tests trastuzumab deruxtecan with immunotherapy in adults with advanced HER2 lung cancer.
Key facts
- Who runs it
- AstraZeneca
- Where
- Changchun, Chengdu, Fuzhou, Shandong, Shanghai, and Zhengzhou, ChinaSee the 6 sitesAlso in 18 other countries, 68 sites
- Registry title
- Phase Ib Study of the Safety of T-DXd and Immunotherapy Agents With and Without Chemotherapy in Advanced or Metastatic HER2+, Non-squamous NSCLC
- Status
- Recruiting
- Phase
- Phase 1
- People taking part
- 304 people, planned
- Started
- 9 Mar 2021
- Expected to end
- 30 Jun 2027
- Type of study
- Interventional, 10 groups
- Treatments tested
- T-DXd
- Durvalumab
- Cisplatin
- Carboplatin
- Pemetrexed
- Volrustomig
- Rilvegostomig
- Record updated
- 13 April 2026
Who can take part
AI summary
From the trial's eligibility criteria. Machine-read from the registry text on this page, so it can be wrong. The registry text below and the trial team decide who can take part.
The trial is looking for adults with advanced or metastatic non-squamous non-small cell lung cancer whose tumor overexpresses HER2, to test the safety of T-DXd with immunotherapy, with or without chemotherapy.
- Age
- 18 years or older
- Sex
- All sexes can join.
- Disease stage
- Non-squamous non-small cell lung cancer that cannot be removed by surgery, locally advanced or metastatic. Measurable disease and ECOG performance status 0 or 1.
- Earlier treatment
- Part 1: the cancer got worse after 1 or 2 lines of systemic therapy. Parts 3, 4 and 5: no earlier treatment for advanced or metastatic disease, and no earlier anti-PD-1, anti-PD-L1, anti-CTLA-4, anti-TIGIT or other experimental immunotherapy.
- Biomarker or test result
- HER2 overexpression confirmed by central review of tumor tissue. Parts 3, 4 and 5: no known genomic alterations or actionable driver kinases that have approved therapies.
Main reasons for not taking part
- Known HER2 mutation
- History of or current ILD/pneumonitis
- Known HIV infection, or active hepatitis B or C
- Spinal cord compression or active brain metastases needing treatment
- Significant heart problems, such as a heart attack within 6 months or symptomatic heart failure
The registry criteria, word for word
Show all 24 criteriaShow less
Who can take part
- 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
Who cannot take part
- HER2 mutation if previously known
- 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
- 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
- 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 thromboembolic events within 3 months before the first dose of IP (limited to pulmonary embolism, deep vein thrombosis, or cerebral venous sinus thrombosis)
- 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
- Active infection including tuberculosis and uncontrolled infection requiring IV antibiotics, antivirals, or antifungals
- 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: 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
Where in China
Also in 18 other countries, 68 sites
- ChangchunHospital not named in the registryContact: AstraZeneca Lung Cancer Study Locator ServiceNot yet recruiting
- ChengduHospital not named in the registryContact: AstraZeneca Lung Cancer Study Locator ServiceNot yet recruiting
- FuzhouHospital not named in the registryContact: AstraZeneca Lung Cancer Study Locator ServiceNot yet recruiting
- ShandongHospital not named in the registryContact: AstraZeneca Lung Cancer Study Locator ServiceNot yet recruiting
- ShanghaiHospital not named in the registryContact: AstraZeneca Lung Cancer Study Locator ServiceTaking people
- ZhengzhouHospital not named in the registryContact: AstraZeneca Lung Cancer Study Locator ServiceNot yet recruiting
About the trial
What the trial wants to find out
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.
The 10 groups in the trial
- Arm 1A: T-DXd, Durvalumab and CisplatinTreatment being tested
T-DXd, Durvalumab and Cisplatin
Treatment: T-DXd, Durvalumab, and Cisplatin
- Arm 1B: T-DXd, Durvalumab and CarboplatinTreatment being tested
T-DXd, Durvalumab and Carboplatin
Treatment: T-DXd, Durvalumab, and Carboplatin
- Arm 1C: T-DXd, Durvalumab and PemetrexedTreatment being tested
T-DXd, Durvalumab and Pemetrexed (Arm not initiated)
Treatment: T-DXd, Durvalumab, and Pemetrexed
- Arm 1D: T-DXdTreatment being tested
T-DXd
Treatment: T-DXd
- Arm 3A: T-DXd and VolrustomigTreatment being tested
Drug: 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
Treatment: T-DXd and Volrustomig
- Arm 3B: T-DXd, Volrustomig and CarboplatinTreatment being tested
Drug: 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
Treatment: T-DXd, Carboplatin, and Volrustomig
- Arm 4A: T-DXd and RilvegostomigTreatment being tested
T-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
Treatment: T-DXd and Rilvegostomig
- Arm 4B T-DXd and Rilvegostomig with CarboplatinTreatment being tested
Drug: 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
Treatment: T-DXd, Carboplatin, and Rilvegostomig
- Arm 5A: T-DXd and VolrustomigTreatment being tested
Drug: 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
Treatment: T-DXd and Volrustomig
- Arm 5B: T-DXd and VolrustomigTreatment being tested
Drug: 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
Treatment: T-DXd and Volrustomig
Results explained
A paper that names this trial, explained in plain words.
Questions to ask the study team
- How often do I need to come in, and for how long each time?
- Are travel costs paid?
- Can I keep my own doctor?
- What happens if I want to stop?
Contact the study team: see the registry record → Contacts and Locations
Print a page for my doctorData and sources
- Registry record
- Listed on ClinicalTrials.gov and on the EU's official list of trials (CTIS).
- Official title
- 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)
- Plain-language title
- Tests trastuzumab deruxtecan with immunotherapy for HER2-positive lung cancerGenerated from the registry record. The registry title is the official one.
- AI summary
- From the trial's eligibility criteria. Read by machine on 12 November 2026.
- Publications
- Trastuzumab Deruxtecan in Patients With HER2-Overexpressing NSCLC: Results From Part 1 of the Open-Label, Multicenter, Phase 1b DESTINY-Lung03 Trial.Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer, 2026
- Record updated
- 13 April 2026