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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04644237




Registration number
NCT04644237
Ethics application status
Date submitted
19/11/2020
Date registered
25/11/2020

Titles & IDs
Public title
Trastuzumab Deruxtecan in Participants With HER2-mutated Metastatic Non-small Cell Lung Cancer (NSCLC)
Scientific title
A Phase 2, Multicenter, Randomized Study of Trastuzumab Deruxtecan in Subjects With HER2-mutated Metastatic Non-small Cell Lung Cancer (NSCLC) (DESTINY-LUNG02)
Secondary ID [1] 0 0
2020-003427-42
Secondary ID [2] 0 0
DS8201-A-U206
Universal Trial Number (UTN)
Trial acronym
DESTINY-LUNG02
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Non-Small Cell Lung Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lung - Mesothelioma
Cancer 0 0 0 0
Lung - Non small cell
Cancer 0 0 0 0
Lung - Small cell

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Trastuzumab deruxtecan

Experimental: Trastuzumab deruxtecan 6.4 mg/kg - Participants will be randomized to receive trastuzumab deruxtecan 6.4 mg/kg administered by intravenous infusion every 3 weeks (Q3W).

Experimental: Trastuzumab deruxtecan 5.4 mg/kg - Participants will be randomized to receive trastuzumab deruxtecan 5.4 mg/kg administered by intravenous infusion every 3 weeks (Q3W).


Treatment: Drugs: Trastuzumab deruxtecan
Trastuzumab deruxtecan 100 mg will be provided as a sterile lyophilized powder and reconstituted with 5 mL water for injection (final concentration 20 mg/mL \[ie, 100 mg/5 mL\]). The study drug will be administered as an intravenous (IV) infusion over 30 to 90 min Q3W ± 2 days. The initial dose of study drug will be infused for 90 ± 10 min.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Participants With Confirmed Objective Response Rate by Blinded Independent Central Review Following Intravenous Administration of Trastuzumab Deruxtecan in Participants With Metastatic Non-small Cell Lung Cancer
Timepoint [1] 0 0
9 months after the last participant is randomized to data cut off, up to approximately 21 months
Secondary outcome [1] 0 0
Percentage of Participants With Confirmed Objective Response Rate by Investigator Following Intravenous Administration of Trastuzumab Deruxtecan in Participants With Metastatic Non-small Cell Lung CancerTumors
Timepoint [1] 0 0
9 months after the last participant is randomized or later to data cut off, up to approximately 35 months
Secondary outcome [2] 0 0
Duration of Response Following Intravenous Administration of Trastuzumab Deruxtecan in Participants With Metastatic Non-small Cell Lung Cancer
Timepoint [2] 0 0
9 months after the last participant is randomized or later to data cut off, up to approximately 35 months
Secondary outcome [3] 0 0
Disease Control Rate Following Intravenous Administration of Trastuzumab Deruxtecan in Participants With Metastatic Non-small Cell Lung Cancer
Timepoint [3] 0 0
9 months after the last participant is randomized or later to data cut off, up to approximately 35 months
Secondary outcome [4] 0 0
Progression-free Survival Following Intravenous Administration of Trastuzumab Deruxtecan in Participants With Metastatic Non-small Cell Lung Cancer
Timepoint [4] 0 0
9 months after the last participant is randomized or later to data cut off, up to approximately 35 months
Secondary outcome [5] 0 0
Overall Survival Following Intravenous Administration of Trastuzumab Deruxtecan in Participants With Metastatic Non-small Cell Lung Cancer Tumors
Timepoint [5] 0 0
9 months after the last participant is randomized or later to data cut off, up to approximately 35 months
Secondary outcome [6] 0 0
The Percentage of Participants Reporting Treatment-emergent Adverse Events Following Intravenous Administration of Trastuzumab Deruxtecan in Participants With Metastatic Non-small Cell Lung Cancer Tumors
Timepoint [6] 0 0
9 months after the last participant is randomized or later to data cut off, up to approximately 35 months
Secondary outcome [7] 0 0
Pharmacokinetic Parameter Maximum Serum Concentration (Cmax) for Trastuzumab Deruxtecan, Total Anti-HER2 Antibody, and Active Metabolite MAAA-1181a
Timepoint [7] 0 0
Cycle 1 Day 1; Cycle 2 Day 1, and Cycle 3 Day 1: pre- and post-dose; Cycle 1 Day 8: 7 days post-dose; Cycle 1 Day 15: 14 days post-dose; Cycle 4 Day 1 and Cycle 6 Day 1: pre-dose (each cycle is 21 days)
Secondary outcome [8] 0 0
Pharmacokinetic Parameter Minimum Observed Concentration (Ctrough) for Trastuzumab Deruxtecan, Total Anti-HER2 Antibody, and Active Metabolite MAAA-1181a
Timepoint [8] 0 0
Cycle 1 Day 1; Cycle 2 Day 1, and Cycle 3 Day 1: pre- and post-dose; Cycle 1 Day 8: 7 days post-dose; Cycle 1 Day 15: 14 days post-dose; Cycle 4 Day 1 and Cycle 6 Day 1: pre-dose (each cycle is 21 days)
Secondary outcome [9] 0 0
Pharmacokinetic Parameter Area Under the Serum Concentration-Time Curve (AUC) for Trastuzumab Deruxtecan, Total Anti-HER2 Antibody, and Active Metabolite MAAA-1181a
Timepoint [9] 0 0
Cycle 1 Day 1; Cycle 2 Day 1, and Cycle 3 Day 1: pre- and post-dose; Cycle 1 Day 8: 7 days post-dose; Cycle 1 Day 15: 14 days post-dose; Cycle 4 Day 1 and Cycle 6 Day 1: pre-dose (each cycle is 21 days)
Secondary outcome [10] 0 0
Incidence of Anti-Drug Antibodies (ADA) Following Intravenous Administration of Trastuzumab Deruxtecan in Participants With Metastatic Non-small Cell Lung Cancer Tumors
Timepoint [10] 0 0
Pre-dose on Day 1 of Cycles 1, 2 and 4, and then every 4 cycles (each cycle is 21 days)
Secondary outcome [11] 0 0
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life Questionnaire (QLQ-C30) and EORTC Quality of Life Questionnaire for Lung Cancer Trials (QLQ-LC13) Scores
Timepoint [11] 0 0
On Day 1 of every cycle (each cycle is 21 days), and at end of treatment visit 40-day follow-up visit
Secondary outcome [12] 0 0
Time to Deterioration in European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life Questionnaire (QLQ-C30) Scores
Timepoint [12] 0 0
On Day 1 of every cycle (each cycle is 21 days), and at end of treatment visit 40-day follow-up visit

Eligibility
Key inclusion criteria
* Written informed consent
* Men or women =18 years, follow local regulatory requirements if the legal age of the consent for study participation is >18 years
* Pathologically documented metastatic NSCLC with a known activating HER2 mutation. Note: A HER2 mutation documented only from a liquid biopsy samples cannot be used for enrollment.
* Had previous treatment including platinum therapy in the metastatic/locally advanced setting and not amenable to curative surgery or radiation. Participant must have progressed during or after the last treatment regimen or discontinued because of unacceptable toxicity.
* Presence of at least 1 measurable lesion confirmed by the blinded Independent Central Review based on RECIST version 1.1
* Willing and able to provide an archival tumor tissue sample. A fresh biopsy is required if an archival tumor tissue sample cannot be supplied. Resection and core needle biopsy are acceptable. Fine needle aspirates or cell block are not acceptable.
* Eastern Cooperative Oncology Group performance status 0 to 1
* Left ventricular ejection fraction = 50% within 28 days before randomization Resection and core needle biopsy are acceptable - Adequate organ function as specified in protocol within 14 days before randomization
* Adequate treatment washout period before randomization
* Participants of reproductive/childbearing potential agree to use a highly effective form of contraception (or avoid intercourse) during study period and up to 7 months (females) and 4 months (males) after last study dose
* Males should not freeze or donate sperm throughout the study period up to at least 4 months after last study dose; females should not donate or retrieve ova for their own use throughout the study period and up to at least 7 months after last study dose
* Life expectancy 3 months or more
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Known driver mutation in the epidermal growth factor receptor (EGFR), BRAF, or MET exon 14 gene or a known anaplastic lymphoma kinase (ALK), ROS1, RET, or NTRK fusion
* Medical history of myocardial infarction within 6 months before randomization, symptomatic congestive heart failure (CHF) (New York Heart Association Class II to IV). Participants with troponin levels above upper limit of normal at screening (as defined by the manufacturer) and without any myocardial infarction (MI)-related symptoms should have a cardiologic consultation before randomization to rule out MI
* Corrected QT interval (QTcF) prolongation > 470 msec (females) or >450 msec (males) based on average of the triplicate12-lead electrocardiogram at screening
* History of non-infectious interstitial lung disease (ILD)/pneumonitis that required steroids, current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening
* 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
* Multiple primary malignancies within 3 years, except adequately resected non-melanoma skin cancer, curatively treated in-situ disease, or other solid tumors curatively treated
* History of severe hypersensitivity reactions to either the drug substances or inactive ingredients in the drug product
* History of severe hypersensitivity reactions to other monoclonal antibodies
* Uncontrolled infection requiring IV antibiotics, antivirals, or antifungals
* Substance abuse or any other medical conditions such as clinically significant cardiac or psychological conditions, that may, in the opinion of the investigator, interfere with the participant's participation in the clinical study or evaluation of the clinical study results
* Known human immunodeficiency virus (HIV) infection
* Known active, clinically relevant liver disease (eg, active hepatitis B, or active hepatitis C) such as those with serologic evidence of viral infection within 28 days of Cycle 1, Day 1
* Unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet resolved to Grade = 1 or baseline
* Pregnant, breastfeeding, or planning to become pregnant
* Otherwise considered inappropriate for the study by the Investigator
* Lung-specific intercurrent clinically significant illnesses including, but not limited to, any underlying pulmonary disorder (eg. pulmonary emboli within three months of the study randomization, severe asthma, severe COPD, restrictive lung disease, pleural effusion, etc.)
* Any autoimmune, connective tissue or inflammatory disorders (e.g., Rheumatoid arthritis, Sjogren's, sarcoidosis etc.) where there is documented, or a suspicion of pulmonary involvement at the time of screening
* Prior complete pneumonectomy
* Had prior treatment with any agent, including an antibody drug conjugate (ADC), containing a chemotherapeutic agent targeting topoisomerase I

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
19/03/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
23/08/2024
Sample size
Target
Accrual to date
Final
152
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
St John of God Subiaco Hospital - Subiaco
Recruitment hospital [2] 0 0
Princess Alexandra Hospital - Woolloongabba
Recruitment postcode(s) [1] 0 0
6008 - Subiaco
Recruitment postcode(s) [2] 0 0
4102 - Woolloongabba
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Colorado
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Kentucky
Country [4] 0 0
United States of America
State/province [4] 0 0
Massachusetts
Country [5] 0 0
United States of America
State/province [5] 0 0
Michigan
Country [6] 0 0
United States of America
State/province [6] 0 0
Missouri
Country [7] 0 0
United States of America
State/province [7] 0 0
Tennessee
Country [8] 0 0
United States of America
State/province [8] 0 0
Virginia
Country [9] 0 0
Canada
State/province [9] 0 0
Toronto
Country [10] 0 0
France
State/province [10] 0 0
Lyon
Country [11] 0 0
France
State/province [11] 0 0
Marseille
Country [12] 0 0
France
State/province [12] 0 0
Rennes
Country [13] 0 0
France
State/province [13] 0 0
Saint-Herblain
Country [14] 0 0
France
State/province [14] 0 0
Toulouse
Country [15] 0 0
France
State/province [15] 0 0
Villejuif
Country [16] 0 0
Italy
State/province [16] 0 0
Lucca
Country [17] 0 0
Italy
State/province [17] 0 0
Milano
Country [18] 0 0
Italy
State/province [18] 0 0
Modena
Country [19] 0 0
Italy
State/province [19] 0 0
Napoli
Country [20] 0 0
Italy
State/province [20] 0 0
Orbassano
Country [21] 0 0
Italy
State/province [21] 0 0
Rozzano
Country [22] 0 0
Japan
State/province [22] 0 0
Chikusa
Country [23] 0 0
Japan
State/province [23] 0 0
Chuo Ku
Country [24] 0 0
Japan
State/province [24] 0 0
Fukuoka
Country [25] 0 0
Japan
State/province [25] 0 0
Kashiwa
Country [26] 0 0
Japan
State/province [26] 0 0
Okayama
Country [27] 0 0
Japan
State/province [27] 0 0
Osaka-sayama
Country [28] 0 0
Korea, Republic of
State/province [28] 0 0
Chungbuk
Country [29] 0 0
Korea, Republic of
State/province [29] 0 0
Seongnam
Country [30] 0 0
Korea, Republic of
State/province [30] 0 0
Seoul
Country [31] 0 0
Netherlands
State/province [31] 0 0
Amsterdam
Country [32] 0 0
Netherlands
State/province [32] 0 0
Rotterdam
Country [33] 0 0
Spain
State/province [33] 0 0
Barcelona
Country [34] 0 0
Spain
State/province [34] 0 0
Madrid
Country [35] 0 0
Spain
State/province [35] 0 0
Pamplona
Country [36] 0 0
Spain
State/province [36] 0 0
Valencia
Country [37] 0 0
Taiwan
State/province [37] 0 0
Taichung
Country [38] 0 0
Taiwan
State/province [38] 0 0
Tainan
Country [39] 0 0
Taiwan
State/province [39] 0 0
Taipei City
Country [40] 0 0
Taiwan
State/province [40] 0 0
Taoyuan

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Daiichi Sankyo
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
AstraZeneca
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Global Clinical Leader
Address 0 0
Daiichi Sankyo
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/

Supporting document/s available: Study protocol, Statistical analysis plan (SAP), Clinical study report (CSR)
When will data be available (start and end dates)?
Studies for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.
Available to whom?
Formal request from qualified scientific and medical researchers on IPD and clinical study documents from clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://vivli.org/ourmember/daiichi-sankyo/


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results are available at https://clinicaltrials.gov/study/NCT04644237