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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04619004




Registration number
NCT04619004
Ethics application status
Date submitted
29/10/2020
Date registered
6/11/2020

Titles & IDs
Public title
HERTHENA-Lung01: Patritumab Deruxtecan in Subjects With Metastatic or Locally Advanced EGFR-mutated Non-Small Cell Lung Cancer
Scientific title
HERTHENA-Lung01: A Phase 2 Randomized Open-Label Study of Patritumab Deruxtecan (U3-1402) in Subjects With Previously Treated Metastatic or Locally Advanced EGFR-mutated Non-Small Cell Lung Cancer (NSCLC)
Secondary ID [1] 0 0
2020-000730-17
Secondary ID [2] 0 0
U31402-A-U201
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Non-Small Cell Lung Cancer Metastatic 0 0
Non-Small Cell Lung Cancer With Mutation in Epidermal Growth Factor Receptor 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 - Patritumab Deruxtecan (Fixed dose)
Treatment: Drugs - Patritumab Deruxtecan (Up-Titration)

Experimental: Study Group 1: Patritumab deruxtecan 5.6 mg/kg - Study Group 1 will be participants with metastatic or locally advanced NSCLC with an EGFR-activating mutation randomized to receive patritumab deruxtecan 5.6 mg/kg IV every 3 weeks (Q3W)

Experimental: Study Group 2: Patritumab deruxtecan Up-Titration - Study Group 2 will be participants with metastatic or locally advanced NSCLC with an EGFR-activating mutation randomized to receive patritumab deruxtecan up-titration IV every 3 weeks (Q3W)


Treatment: Drugs: Patritumab Deruxtecan (Fixed dose)
Patritumab deruxtecan will be dosed at 5.6 mg/kg as an intravenous (IV) infusion administered on Day 1 of each 21-day cycle.

Treatment: Drugs: Patritumab Deruxtecan (Up-Titration)
Patritumab deruxtecan will be dosed as an intravenous (IV) infusion administered at Cycle 1, 3.2 mg/kg; Cycle 2, 4.8 mg/kg; Cycle 3 and subsequent cycles, 6.4 mg/kg administered on Day 1 of each 21-day cycle.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Objective Response Rate (ORR) as Assessed by Blinded Independent Central Review (BICR)
Timepoint [1] 0 0
Data collected from screening until time of disease progression by BICR, death, lost to follow up, study discontinuation, whichever occurs first, assessed up to approximately 21 months
Secondary outcome [1] 0 0
Duration of Response (DoR)
Timepoint [1] 0 0
Data collected from screening until time of disease progression by BICR, death, lost to follow up, study discontinuation, whichever occurs first, assessed up to approximately 21 months
Secondary outcome [2] 0 0
Progression-free Survival (PFS)
Timepoint [2] 0 0
Data collected from screening until time of disease progression by BICR, death, lost to follow up, study discontinuation, whichever occurs first, assessed up to approximately 21 months
Secondary outcome [3] 0 0
Objective Response Rate (ORR) as Assessed by the Investigator
Timepoint [3] 0 0
Data collected from screening until time of disease progression, death, lost to follow up, study discontinuation, whichever occurs first, assessed up to approximately 21 months
Secondary outcome [4] 0 0
Disease Control Rate (DCR)
Timepoint [4] 0 0
Data collected from screening until time of disease progression by BICR, death, lost to follow up, study discontinuation, whichever occurs first, assessed up to approximately 21 months
Secondary outcome [5] 0 0
Time to Tumor Response (TTR)
Timepoint [5] 0 0
Data collected from screening until time of disease progression by BICR, death, lost to follow up, study discontinuation, whichever occurs first, assessed up to approximately 21 months
Secondary outcome [6] 0 0
Best Percentage Change in the Sum of Diameters (SoD) of Measurable Tumors
Timepoint [6] 0 0
Data collected from screening until time of disease progression by BICR, death, lost to follow up, study discontinuation, whichever occurs first, assessed up to approximately 21 months
Secondary outcome [7] 0 0
Overall Survival (OS)
Timepoint [7] 0 0
Death date is collected until the participant discontinues the study or up to approximately 45 months
Secondary outcome [8] 0 0
Incidence of Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Adverse Events of Special Interest (AESIs)
Timepoint [8] 0 0
From baseline up to Day 47 post last dose

Eligibility
Key inclusion criteria
Participants must meet all of the following criteria to be eligible for inclusion in this study.

* Sign and date the tissue informed consent form (ICF) and the main ICF, prior to the start of any study-specific qualification procedures.
* Male or female participants aged =18 years (follow local regulatory requirements if the legal age of consent for study participation is >18 years old).
* Histologically or cytologically documented locally advanced or metastatic NSCLC not amenable to curative surgery or radiation.
* Documentation of radiological disease progression while on/after receiving most recent treatment regimen for locally advanced or metastatic disease. Participants must have received both of the following:

* Prior treatment with osimertinib. Participants receiving an EGFR TKI at the time of signing informed consent should continue to take the EGFR TKI until 5 days prior to Cycle 1 Day 1. Participants in South Korea known to harbor a clinically actionable genomic alteration in addition to EGFR mutation (e.g., anaplastic lymphoma kinase [ALK] or ROS1 protocol oncogene 1 [ROS1] fusion) for which treatment is available must have also received prior treatment with at least 1 approved genotype-directed therapy, unless unable (i.e., if contraindicated). No new testing for these genomic alterations (e.g., ALK or ROS1 fusion) is required for Screening.
* Systemic therapy with at least 1 platinum-based chemotherapy regimen.
* Documentation of an EGFR-activating mutation detected from tumor tissue or blood sample: exon 19 deletion or L858R.
* At least 1 measurable lesion confirmed by BICR as per RECIST v1.1
* Consented and willing to provide required tumor tissue of sufficient quantity and of adequate tumor tissue content. Required tumor tissue can be provided as either:

* Pretreatment tumor biopsy from at least 1 lesion not previously irradiated and amenable to core biopsy OR
* Archival tumor tissue collected from a biopsy performed within 3 months prior to signing of the tissue consent and since progression while on or after treatment with the most recent cancer therapy regimen.
* Eastern Cooperative Oncology Group Performance Standard of 0 or 1 at Screening.
* Has adequate bone marrow reserve and organ function based on local laboratory data within 14 days prior to Cycle 1 Day 1:

* Platelet count : =100,000/mm^3 or =100 × 10^9/L (platelet transfusions are not allowed up to 14 days prior to Cycle 1 Day 1 to meet eligibility)
* Hemoglobin: =9.0 g/dL (transfusion and/or growth factor support is allowed)
* Absolute neutrophil count: =1500/mm^3 or =1.5 × 10^9/L
* Serum creatinine (SCr) or creatinine clearance (CrCl): SCr =1.5 × upper limit of normal (ULN), OR CrCl =30 mL/min as calculated using the Cockcroft-Gault equation or measured CrCl
* Aspartate aminotransferase/alanine aminotransferase: =3 × ULN (if liver metastases are present, =5 × ULN)
* Total bilirubin: =1.5 × ULN if no liver metastases (<3 × ULN in the presence of documented Gilbert's syndrome [unconjugated hyperbilirubinemia] or liver metastases)
* Serum albumin: =2.5 g/dL
* Prothrombin time (PT) or PT-International normalized ratio (INR) and activated partial thromboplastin time (aPTT)/PTT: =1.5 × ULN, except for subjects on coumarin-derivative anticoagulants or other similar anticoagulant therapy, who must have PT-INR within therapeutic range as deemed appropriate by the Investigator
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Participants meeting any exclusion criteria for this study will be excluded from this study.

* Any previous histologic or cytologic evidence of small cell OR combined small cell/non-small cell disease in the archival tumor tissue or pretreatment tumor biopsy.
* Any history of interstitial lung disease (including pulmonary fibrosis or radiation pneumonitis), has current interstitial lung disease (ILD), or is suspected to have such disease by imaging during screening.
* Clinically severe respiratory compromise (based on Investigator's assessment) resulting from intercurrent pulmonary illnesses including, but not limited to:

* Any underlying pulmonary disorder (eg, pulmonary emboli within 3 months prior to the study enrollment, severe asthma, severe chronic obstructive pulmonary disease [COPD]), restrictive lung disease, pleural effusion);
* Any autoimmune, connective tissue or inflammatory disorders with pulmonary involvement (eg, rheumatoid arthritis, Sjogren's syndrome, sarcoidosis); OR prior complete pneumonectomy.
* Is receiving chronic systemic corticosteroids dosed at >10 mg prednisone or equivalent anti-inflammatory or any form of immunosuppressive therapy prior to enrollment. Participants who require use of bronchodilators, inhaled or topical steroids, or local steroid injections may be included in the study.
* Evidence of any leptomeningeal disease.
* Evidence of clinically active spinal cord compression or brain metastases.
* Inadequate washout period prior to Cycle 1 Day 1, defined as:

* Whole brain radiation therapy <14 days or stereotactic brain radiation therapy <7 days;
* Any cytotoxic chemotherapy, investigational agent or other anticancer drug(s) from a previous cancer treatment regimen or clinical study (other than EGFR TKI), <14 days or 5 half-lives, whichever is longer;
* Monoclonal antibodies, other than immune checkpoint inhibitors, such as bevacizumab (anti-VEGF) and cetuximab (anti-EGFR) <28 days;
* Immune checkpoint inhibitor therapy <21 days;
* Major surgery (excluding placement of vascular access) <28 days;
* Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation <28 days or palliative radiation therapy <14 days; or
* Chloroquine or hydroxychloroquine <14 days.
* Prior treatment with an anti-human epidermal growth factor receptor 3 (HER3) antibody or single-agent topoisomerase I inhibitor.
* Prior treatment with an antibody drug conjugate (ADC) that consists of any topoisomerase I inhibitor
* Has unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet resolved to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0, Grade =1 or baseline. Participants with chronic Grade 2 toxicities may be eligible at the discretion of the Investigator after consultation with the Sponsor Medical Monitor or designee.
* Has history of other active malignancy within 3 years prior to enrollment, except:

* Adequately treated non-melanoma skin cancer;
* Superficial bladder tumors (Ta, Tis, T1);
* Adequately treated intraepithelial carcinoma of the cervix uteri;
* Low risk non-metastatic prostate cancer (with Gleason score <7, and following local treatment or ongoing active surveillance);
* Any other curatively treated in situ disease.
* Uncontrolled or significant cardiovascular disease prior to Cycle 1 Day 1
* Active hepatitis B and/or hepatitis C infection, such as those with serologic evidence of viral infection within 28 days of Cycle 1 Day 1.
* Participant with any human immunodeficiency virus (HIV) infection.

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
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
2/02/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
30/01/2026
Actual
Sample size
Target
Accrual to date
Final
277
Recruitment in Australia
Recruitment state(s)
NSW,VIC,WA
Recruitment hospital [1] 0 0
Blacktown Hospital - Blacktown
Recruitment hospital [2] 0 0
The Chris O'Brien Lifehouse - Camperdown
Recruitment hospital [3] 0 0
St George Public Hospital - Kogarah
Recruitment hospital [4] 0 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment hospital [5] 0 0
St John of God Subiaco Hospital - Subiaco
Recruitment hospital [6] 0 0
Princess Alexandra Hospital - Woolloongabba
Recruitment postcode(s) [1] 0 0
2148 - Blacktown
Recruitment postcode(s) [2] 0 0
2050 - Camperdown
Recruitment postcode(s) [3] 0 0
2217 - Kogarah
Recruitment postcode(s) [4] 0 0
3000 - Melbourne
Recruitment postcode(s) [5] 0 0
6008 - Subiaco
Recruitment postcode(s) [6] 0 0
4102 - Woolloongabba
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
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United States of America
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California
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Colorado
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Florida
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Georgia
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United States of America
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Illinois
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Maryland
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United States of America
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Massachusetts
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Michigan
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New York
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United States of America
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North Carolina
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Ohio
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Oregon
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Tennessee
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Virginia
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Washington
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Austria
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Wien
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Belgium
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Leuven
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Bulgaria
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Panagyurishte
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Bulgaria
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Russe
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Bulgaria
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Sofia
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China
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Beijing
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China
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Chang chun
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China
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Chengdu
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Guangzhou
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China
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Hangzhou
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China
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Harbin
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China
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Nanjing
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China
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Shanghai
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China
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Shenyang
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China
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Wuhan
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China
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Zhengzhou
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France
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Haute-Garonne
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France
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Loire-Atlantique
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Rhone
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Rennes
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France
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Villejuif
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Germany
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Nordrhein-Westfalen
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Germany
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North Rhine-Westphal
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Germany
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Schleswig-Holstein
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Germany
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Dresden
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Germany
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Koeln
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Italy
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Province Of Parma
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Italy
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Turin
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Italy
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Meldola
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Italy
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Milano
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Rozzano
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Chiba
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Hyogo
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Koto
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Miyagi
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Osaka
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Shizuoka
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Tokyo
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Chuo Ku Niigata-shi
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Japan
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Fukuoka
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Japan
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Sapporo
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Korea, Republic of
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Seoul
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Korea, Republic of
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Cheongju-si
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Korea, Republic of
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Daegu
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Korea, Republic of
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Goyang-si
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Korea, Republic of
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Seongnam
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Netherlands
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Amsterdam
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Singapore
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Singapore
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Spain
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Andalucia
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Spain
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Cataluã'a
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Spain
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Madrid
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Spain
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Barcelona
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Spain
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Málaga
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Spain
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Zaragoza
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Taiwan
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Gao Xiong Shi
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Taiwan
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Tai Nan Shi
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Taiwan
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Kaohsiung City
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Taiwan
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Niaosong
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Taiwan
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Taichung
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Taiwan
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Taipei
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Taiwan
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Taoyuan
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United Kingdom
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Birmingham
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United Kingdom
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London
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United Kingdom
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Manchester

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
Daiichi Sankyo Co., Ltd.
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Commercial sector/industry
Name [2] 0 0
Merck Sharp & Dohme LLC
Address [2] 0 0
Country [2] 0 0

Ethics approval
Ethics application status

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

Contacts
Principal investigator
Name 0 0
Medical Director
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/NCT04619004