Please note that the copy function is not enabled for this field.
If you wish to
modify
existing outcomes, please copy and paste the current outcome text into the Update field.
LOGIN
CREATE ACCOUNT
LOGIN
CREATE ACCOUNT
MY TRIALS
REGISTER TRIAL
FAQs
HINTS AND TIPS
DEFINITIONS
Trial Review
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this
information for consumers
Download to PDF
Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/ct2/show/NCT04686305
Registration number
NCT04686305
Ethics application status
Date submitted
8/12/2020
Date registered
28/12/2020
Date last updated
6/06/2024
Titles & IDs
Public 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
Query!
Scientific 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)
Query!
Secondary ID [1]
0
0
2020-003260-31
Query!
Secondary ID [2]
0
0
D967YC00001
Query!
Universal Trial Number (UTN)
Query!
Trial acronym
DL03
Query!
Linked study record
Query!
Health condition
Health condition(s) or problem(s) studied:
Locally Advanced or Metastatic Non-Small Cell Lung Cancer
0
0
Query!
Condition category
Condition code
Cancer
0
0
0
0
Query!
Lung - Mesothelioma
Query!
Cancer
0
0
0
0
Query!
Lung - Non small cell
Query!
Cancer
0
0
0
0
Query!
Lung - Small cell
Query!
Intervention/exposure
Study type
Interventional
Query!
Description of intervention(s) / exposure
Treatment: Drugs - T-DXd
Other interventions - Durvalumab
Treatment: Drugs - Cisplatin
Treatment: Drugs - Carboplatin
Treatment: Drugs - Pemetrexed
Treatment: Drugs - Volrustomig
Treatment: Drugs - Rilvegostomig
Experimental: Arm 1A: T-DXd, Durvalumab and Cisplatin - T-DXd, Durvalumab and Cisplatin
Experimental: Arm 1B: T-DXd, Durvalumab and Carboplatin - T-DXd, Durvalumab and Carboplatin
Experimental: Arm 1C: T-DXd, Durvalumab and Pemetrexed - T-DXd, Durvalumab and Pemetrexed (Arm not initiated)
Experimental: Arm 1D: T-DXd - T-DXd
Experimental: Arm 3A: T-DXd and Volrustomig - 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
Experimental: Arm 3B: T-DXd, Volrustomig and Carboplatin - 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
Experimental: Arm 4A: T-DXd and Rilvegostomig - 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
Experimental: Arm 4B T-DXd and Rilvegostomig with Carboplatin - 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: Drugs: T-DXd
T-DXd: administered as an IV infusion
Other interventions: Durvalumab
Durvalumab: administered as an IV infusion
Treatment: Drugs: Cisplatin
Cisplatin: administered as an IV infusion
Treatment: Drugs: Carboplatin
Carboplatin: administered as an IV infusion
Treatment: Drugs: Pemetrexed
Pemetrexed: administered as an IV infusion (drug not used)
Treatment: Drugs: Volrustomig
Volrustomig: administered as an IV infusion
Treatment: Drugs: Rilvegostomig
Rilvegostomig: administered as an IV infusion
Query!
Intervention code [1]
0
0
Treatment: Drugs
Query!
Intervention code [2]
0
0
Other interventions
Query!
Comparator / control treatment
Query!
Control group
Query!
Outcomes
Primary outcome [1]
0
0
Frequency of AEs and SAEs
Query!
Assessment method [1]
0
0
Occurrence of AEs and SAEs graded according to NCI CTCAE v5.0
Query!
Timepoint [1]
0
0
Safety and tolerability (and to determine RP2D) will be assessed for approximately 20 months from informed consent
Query!
Secondary outcome [1]
0
0
Confirmed Objective Response Rate (ORR)
Query!
Assessment method [1]
0
0
Confirmed ORR per RECIST 1.1 is the percentage of patients with Complete Response or Partial Response that is subsequently confirmed, based on investigator assessment
Query!
Timepoint [1]
0
0
An average of approximately 12 months
Query!
Secondary outcome [2]
0
0
Duration of Response (DoR)
Query!
Assessment method [2]
0
0
DOR is defined as the time from the date of first documented response until the date of documented progression or death, based on RECIST 1.1 assessment
Query!
Timepoint [2]
0
0
An average of approximately 20 months
Query!
Secondary outcome [3]
0
0
Disease Control Rate (DCR)
Query!
Assessment method [3]
0
0
DCR is the percentage of patients who have a best overall response of complete response (CR) or partial response (PR) or stable disease (SD), based on RECIST 1.1 assessment. DCR is assessed at 6 and 12 weeks
Query!
Timepoint [3]
0
0
An average of approximately 12 months
Query!
Secondary outcome [4]
0
0
Progression-free survival (PFS)
Query!
Assessment method [4]
0
0
PFS is the time from first dose of study treatment until the date of objective disease progression or death, based on RECIST 1.1 assessment
Query!
Timepoint [4]
0
0
An average of approximately 20 months
Query!
Secondary outcome [5]
0
0
Overall survival (OS)
Query!
Assessment method [5]
0
0
OS is the time form the date of first dose of study treatment until death due to any cause
Query!
Timepoint [5]
0
0
An average of approximately 20 months
Query!
Secondary outcome [6]
0
0
Pharmacokinetics (PK) assessed by the serum concentration of T-DXd, total anti-HER2 antibody, and MAAA-1181 in all arms
Query!
Assessment method [6]
0
0
Individual patient data and descriptive statistics will be provided for serum concentration data at each time point for T-DXd, total anti-HER2 antibody and MAAA-1181a
Query!
Timepoint [6]
0
0
An average of approximately 20 months
Query!
Secondary outcome [7]
0
0
Pharmacokinetics (PK) assessed by the serum concentration of durvalumab in study arms including T-DXd in combination with durvalumab
Query!
Assessment method [7]
0
0
Individual patient data and descriptive statistics will be provided for serum concentration data at each time point for durvalumab, including T-DXd in combination with durvalumab
Query!
Timepoint [7]
0
0
An average of approximately 20 months
Query!
Secondary outcome [8]
0
0
Pharmacokinetics (PK) assessed by the serum concentration of volrustomig in study arms including T-DXd in combination with volrustomig
Query!
Assessment method [8]
0
0
Individual patient data and descriptive statistics will be provided for serum concentration data at each time point for volrustomig, including T-DXd in combination with volrustomig
Query!
Timepoint [8]
0
0
An average of approximately 20 months
Query!
Secondary outcome [9]
0
0
Pharmacokinetics (PK) assessed by the serum concentration of rilvegostomig in study arms including T-DXd in combination with rilvegostomig
Query!
Assessment method [9]
0
0
Individual patient data and descriptive statistics will be provided for serum concentration data at each time point for rilvegostomig, including T- DXd in combination with rilvegostomig
Query!
Timepoint [9]
0
0
An average of approximately 20 months
Query!
Secondary outcome [10]
0
0
The immunogenicity of T-DXd, durvalumab, volrustomig and rilvegostomig assessed by the presence of ADAs for T-DXd, durvalumab, volrustomig, or rilvegostomig
Query!
Assessment method [10]
0
0
Individual participant data and descriptive statistics will be provided for data at each time point for each dose level for T-DXd, durvalumab or volrustomig, or rilvegostomig
Query!
Timepoint [10]
0
0
An average of approximately 20 months
Query!
Eligibility
Key inclusion criteria
Inclusion criteria:
- 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 and 4: 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 and 4: 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 and part 4: Minimum body weight of 35 kg.
Query!
Minimum age
18
Years
Query!
Query!
Maximum age
No limit
Query!
Query!
Sex
Both males and females
Query!
Can healthy volunteers participate?
No
Query!
Key exclusion criteria
Exclusion criteria:
- 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 and Part 4: 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 and Part 4: 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 and 4 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 and Part 4: 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 and Part 4: 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).
Query!
Study design
Purpose of the study
Treatment
Query!
Allocation to intervention
Randomised controlled trial
Query!
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Query!
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Query!
Masking / blinding
Open (masking not used)
Query!
Who is / are masked / blinded?
Query!
Query!
Query!
Query!
Intervention assignment
Parallel
Query!
Other design features
Query!
Phase
Phase 1
Query!
Type of endpoint/s
Query!
Statistical methods / analysis
Query!
Recruitment
Recruitment status
Recruiting
Query!
Data analysis
Query!
Reason for early stopping/withdrawal
Query!
Other reasons
Query!
Date of first participant enrolment
Anticipated
Query!
Actual
9/03/2021
Query!
Date of last participant enrolment
Anticipated
Query!
Actual
Query!
Date of last data collection
Anticipated
23/12/2025
Query!
Actual
Query!
Sample size
Target
248
Query!
Accrual to date
Query!
Final
Query!
Recruitment in Australia
Recruitment state(s)
Query!
Recruitment hospital [1]
0
0
Research Site - Adelaide
Query!
Recruitment hospital [2]
0
0
Research Site - Heidelberg
Query!
Recruitment hospital [3]
0
0
Research Site - Nedlands
Query!
Recruitment postcode(s) [1]
0
0
5000 - Adelaide
Query!
Recruitment postcode(s) [2]
0
0
3084 - Heidelberg
Query!
Recruitment postcode(s) [3]
0
0
6009 - Nedlands
Query!
Recruitment outside Australia
Country [1]
0
0
United States of America
Query!
State/province [1]
0
0
California
Query!
Country [2]
0
0
United States of America
Query!
State/province [2]
0
0
Kansas
Query!
Country [3]
0
0
United States of America
Query!
State/province [3]
0
0
Maryland
Query!
Country [4]
0
0
United States of America
Query!
State/province [4]
0
0
Michigan
Query!
Country [5]
0
0
United States of America
Query!
State/province [5]
0
0
New York
Query!
Country [6]
0
0
United States of America
Query!
State/province [6]
0
0
Texas
Query!
Country [7]
0
0
United States of America
Query!
State/province [7]
0
0
Virginia
Query!
Country [8]
0
0
United States of America
Query!
State/province [8]
0
0
Washington
Query!
Country [9]
0
0
Belgium
Query!
State/province [9]
0
0
Edegem
Query!
Country [10]
0
0
Canada
Query!
State/province [10]
0
0
Manitoba
Query!
Country [11]
0
0
Canada
Query!
State/province [11]
0
0
Ontario
Query!
Country [12]
0
0
Canada
Query!
State/province [12]
0
0
Quebec
Query!
Country [13]
0
0
France
Query!
State/province [13]
0
0
Bordeaux Cedex
Query!
Country [14]
0
0
France
Query!
State/province [14]
0
0
Dijon
Query!
Country [15]
0
0
France
Query!
State/province [15]
0
0
Pierre Benite Cedex
Query!
Country [16]
0
0
France
Query!
State/province [16]
0
0
Saint Herblain
Query!
Country [17]
0
0
France
Query!
State/province [17]
0
0
Villejuif Cedex
Query!
Country [18]
0
0
Israel
Query!
State/province [18]
0
0
Kfar-Saba
Query!
Country [19]
0
0
Israel
Query!
State/province [19]
0
0
Tel Hashomer
Query!
Country [20]
0
0
Italy
Query!
State/province [20]
0
0
Milano
Query!
Country [21]
0
0
Italy
Query!
State/province [21]
0
0
Monza
Query!
Country [22]
0
0
Italy
Query!
State/province [22]
0
0
Napoli
Query!
Country [23]
0
0
Italy
Query!
State/province [23]
0
0
Padova
Query!
Country [24]
0
0
Korea, Republic of
Query!
State/province [24]
0
0
Cheongju-si
Query!
Country [25]
0
0
Korea, Republic of
Query!
State/province [25]
0
0
Goyang-si
Query!
Country [26]
0
0
Korea, Republic of
Query!
State/province [26]
0
0
Jinju-si
Query!
Country [27]
0
0
Korea, Republic of
Query!
State/province [27]
0
0
Seoul
Query!
Country [28]
0
0
Malaysia
Query!
State/province [28]
0
0
George Town
Query!
Country [29]
0
0
Malaysia
Query!
State/province [29]
0
0
Kuala Lumpur
Query!
Country [30]
0
0
Malaysia
Query!
State/province [30]
0
0
Kuching
Query!
Country [31]
0
0
Malaysia
Query!
State/province [31]
0
0
Selangor
Query!
Country [32]
0
0
Netherlands
Query!
State/province [32]
0
0
Amsterdam
Query!
Country [33]
0
0
Philippines
Query!
State/province [33]
0
0
Bacolod
Query!
Country [34]
0
0
Philippines
Query!
State/province [34]
0
0
Cebu City
Query!
Country [35]
0
0
Philippines
Query!
State/province [35]
0
0
Davao City
Query!
Country [36]
0
0
Philippines
Query!
State/province [36]
0
0
Manila
Query!
Country [37]
0
0
Philippines
Query!
State/province [37]
0
0
Quezon City
Query!
Country [38]
0
0
Philippines
Query!
State/province [38]
0
0
San Juan
Query!
Country [39]
0
0
Philippines
Query!
State/province [39]
0
0
Taguig City
Query!
Country [40]
0
0
Poland
Query!
State/province [40]
0
0
Gdansk
Query!
Country [41]
0
0
Poland
Query!
State/province [41]
0
0
Kraków
Query!
Country [42]
0
0
Poland
Query!
State/province [42]
0
0
Olsztyn
Query!
Country [43]
0
0
Poland
Query!
State/province [43]
0
0
Tomaszów Mazowiecki
Query!
Country [44]
0
0
Poland
Query!
State/province [44]
0
0
Warszawa
Query!
Country [45]
0
0
Singapore
Query!
State/province [45]
0
0
Singapore
Query!
Country [46]
0
0
Spain
Query!
State/province [46]
0
0
Badalona
Query!
Country [47]
0
0
Spain
Query!
State/province [47]
0
0
Madrid
Query!
Country [48]
0
0
Spain
Query!
State/province [48]
0
0
Sevilla
Query!
Country [49]
0
0
Spain
Query!
State/province [49]
0
0
Valencia
Query!
Country [50]
0
0
Taiwan
Query!
State/province [50]
0
0
Kaohsiung city
Query!
Country [51]
0
0
Taiwan
Query!
State/province [51]
0
0
Taichung City
Query!
Country [52]
0
0
Taiwan
Query!
State/province [52]
0
0
Taichung
Query!
Country [53]
0
0
Taiwan
Query!
State/province [53]
0
0
Tainan
Query!
Country [54]
0
0
Taiwan
Query!
State/province [54]
0
0
Taipei
Query!
Country [55]
0
0
Taiwan
Query!
State/province [55]
0
0
Taoyuan
Query!
Country [56]
0
0
Thailand
Query!
State/province [56]
0
0
Bangkok
Query!
Country [57]
0
0
Thailand
Query!
State/province [57]
0
0
Hat Yai
Query!
Country [58]
0
0
Thailand
Query!
State/province [58]
0
0
Khon Kaen
Query!
Country [59]
0
0
Thailand
Query!
State/province [59]
0
0
Muang
Query!
Country [60]
0
0
Turkey
Query!
State/province [60]
0
0
Ankara
Query!
Country [61]
0
0
Turkey
Query!
State/province [61]
0
0
Bornova-Izmir
Query!
Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Query!
Name
AstraZeneca
Query!
Address
Query!
Country
Query!
Other collaborator category [1]
0
0
Commercial sector/Industry
Query!
Name [1]
0
0
Daiichi Sankyo
Query!
Address [1]
0
0
Query!
Country [1]
0
0
Query!
Ethics approval
Ethics application status
Query!
Summary
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.
Query!
Trial website
https://clinicaltrials.gov/ct2/show/NCT04686305
Query!
Trial related presentations / publications
Query!
Public notes
Query!
Contacts
Principal investigator
Name
0
0
Query!
Address
0
0
Query!
Country
0
0
Query!
Phone
0
0
Query!
Fax
0
0
Query!
Email
0
0
Query!
Contact person for public queries
Name
0
0
AstraZeneca Clinical Study Information Center
Query!
Address
0
0
Query!
Country
0
0
Query!
Phone
0
0
1-877-240-9479
Query!
Fax
0
0
Query!
Email
0
0
[email protected]
Query!
Contact person for scientific queries
Summary Results
For IPD and results data, please see
https://clinicaltrials.gov/ct2/show/NCT04686305
Download to PDF