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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT04129502




Registration number
NCT04129502
Ethics application status
Date submitted
7/10/2019
Date registered
16/10/2019
Date last updated
17/05/2024

Titles & IDs
Public title
TAK-788 as First-Line Treatment Versus Platinum-Based Chemotherapy for Non-Small Cell Lung Cancer (NSCLC) With EGFR Exon 20 Insertion Mutations
Scientific title
A Randomized Phase 3 Multicenter Open-Label Study to Compare the Efficacy of TAK-788 as First-Line Treatment Versus Platinum-Based Chemotherapy in Patients With Non-Small Cell Lung Cancer With EGFR Exon 20 Insertion Mutations
Secondary ID [1] 0 0
NL20191212
Secondary ID [2] 0 0
TAK-788-3001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Advanced/Metastatic Non-Small Cell Lung Cancer (NSCLC) 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 - TAK-788
Treatment: Drugs - Pemetrexed
Treatment: Drugs - Cisplatin
Treatment: Drugs - Carboplatin

Experimental: TAK-788 Group (Arm A) - TAK-788 160 milligram (mg) with or without food, capsules, orally, once daily until the participants experience PD as assessed by blinded IRC, intolerable toxicity, or another discontinuation criteria.

Active Comparator: Platinum-based Chemotherapy Group (Arm B) - Pemetrexed 500 milligram per meter square (mg/m^2) plus cisplatin 75 mg/m^2, infusion, IV, once on Day 1 of 21-day cycle pemetrexed 500 mg/m^2 plus carboplatin, infusion, IV, once at a dose calculated to produce area under curve (AUC) of 5 milligram*minute per milliliter (mg*min/mL) on Day 1 of 21-day cycle until the participants experience PD as assessed by blinded IRC, intolerable toxicity, or another discontinuation criteria. Pemetrexed/cisplatin or pemetrexed/carboplatin will be repeated every 3 weeks for 4 cycles, followed by maintenance treatment with pemetrexed 500 mg/m^2, on Day 1 of a 21-day cycle thereafter.


Treatment: Drugs: TAK-788
TAK-788 capsule

Treatment: Drugs: Pemetrexed
Pemetrexed IV infusion

Treatment: Drugs: Cisplatin
Cisplatin IV infusion

Treatment: Drugs: Carboplatin
Carboplatin IV infusion
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression Free Survival (PFS) as Assessed by Blinded Independent Review Committee (IRC) per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
Timepoint [1] 0 0
Up to approximately 40 months after the first participant is randomized
Secondary outcome [1] 0 0
Confirmed Objective Response Rate (ORR) as Assessed by Blinded Independent Review Committee (IRC) per RECIST Version 1.1
Timepoint [1] 0 0
Up to approximately 40 months after the first participant is randomized
Secondary outcome [2] 0 0
Overall Survival (OS)
Timepoint [2] 0 0
Up to approximately 40 months after the first participant is randomized
Secondary outcome [3] 0 0
Progression Free Survival (PFS) as Assessed by the Investigator
Timepoint [3] 0 0
Up to approximately 40 months after the first participant is randomized
Secondary outcome [4] 0 0
Confirmed Objective Response Rate (ORR) as Assessed by the Investigator
Timepoint [4] 0 0
Up to approximately 40 months after the first participant is randomized
Secondary outcome [5] 0 0
Duration of Response, as Assessed by the Blinded Independent Review Committee (IRC) and the Investigator
Timepoint [5] 0 0
Up to approximately 40 months after the first participant is randomized
Secondary outcome [6] 0 0
Time to Response, as Assessed by the Blinded Independent Review Committee (IRC) and the Investigator
Timepoint [6] 0 0
Up to approximately 40 months after the first participant is randomized
Secondary outcome [7] 0 0
Disease Control Rate (DCR) as Assessed by the Blinded Independent Review Committee (IRC) and the Investigator
Timepoint [7] 0 0
Up to approximately 40 months after the first participant is randomized
Secondary outcome [8] 0 0
Patient-reported Symptoms, Functioning, and Health-related Quality of Life (HRQoL) as Assessed by the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30
Timepoint [8] 0 0
Up to approximately 40 months after the first participant is randomized
Secondary outcome [9] 0 0
Participant-reported Symptoms as Assessed by the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire, Lung Cancer Module (QLQ-LC13)
Timepoint [9] 0 0
Up to approximately 40 months after the first participant is randomized

Eligibility
Key inclusion criteria
- Male or female adult patients (aged 18 years or older)

- Histologically or cytologically confirmed nonsquamous cell locally advanced not
suitable for definitive therapy, recurrent, or metastatic (Stage IV) NSCLC

- Documented epidermal growth factor receptor (EGFR) in-frame exon 20 insertion mutation
assessed by a clinical laboratory improvements amendment (CLIA)-certified (US sites)
or an accredited (outside of the US) local laboratory The EGFR exon 20 insertion
mutation can be either alone or in combination with other EGFR or human epidermal
growth factor receptor 2 (HER2) mutations except EGFR mutations for which there are
approved anti-EGFR tyrosine kinase inhibitors [TKIs] (ie, exon 19 del, L858R, T790M,
L861Q, G719X, or S768I, where X is any other amino acid)

- Adequate tumor tissue available, either from primary or metastatic sites, for central
laboratory confirmation of EGFR exon 20 insertion mutation

- At least 1 measurable lesion per RECIST Version 1.1

- Life expectancy =3 months

- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1

- Adequate organ and hematologic function as defined by blood transfusions with a
recommended >/ 14 day washout period.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Received prior systemic treatment for locally advanced or metastatic disease,
including local administration, such as intra-pleural injection of anticancer
medication with the exception noted below:

- Neoadjuvant or adjuvant chemotherapy/immune therapy for Stage I to III or
combined modality chemotherapy/radiation for locally advanced disease is allowed
if completed >6 months before the development of metastatic disease.

- Received radiotherapy =14 days before randomization or has not recovered from
radiotherapy-related toxicities

- Received a moderate or strong cytochrome P450 (CYP)3A inhibitor or moderate or strong
CYP3A inducer within 10 days before first dose of TAK-788

- Have been diagnosed with another primary malignancy other than NSCLC

- Have current spinal cord compression or leptomeningeal disease

- Have uncontrolled hypertension. Participants with hypertension should be under
treatment on study entry to control blood pressure

- Received a live vaccine within 4 weeks before randomization per Summary of product
characteristics (SmPCs) for pemetrexed, cisplatin, and carboplatin

- Taking medication(s) known to be associated with the development of torsades de
pointes.

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 3
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
10/01/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
30/12/2024
Actual
Sample size
Target
Accrual to date
Final
354
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA
Recruitment hospital [1] 0 0
GenesisCare North Shore - St Leonards
Recruitment hospital [2] 0 0
Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [3] 0 0
Flinders Medical Centre - Bedford Park
Recruitment postcode(s) [1] 0 0
2065 - St Leonards
Recruitment postcode(s) [2] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [3] 0 0
5042 - Bedford Park
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
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United States of America
State/province [2] 0 0
Florida
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United States of America
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Illinois
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United States of America
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Maryland
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United States of America
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Massachusetts
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United States of America
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Tennessee
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Virginia
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Austria
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Wien
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Belgium
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Brussels
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Belgium
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Hainaut
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Belgium
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Oost-Vlaanderen
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Canada
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British Columbia
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Canada
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Ontario
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Canada
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Quebec
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China
State/province [15] 0 0
Beijing
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China
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Henan
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China
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Jilin
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China
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Chengdu
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China
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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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Shanghai
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China
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Wuhan
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Calvados
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Nord
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Rhone
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Grenoble
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Marseille
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Montpellier
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France
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Paris
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France
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Strasbourg
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France
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Toulouse
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Germany
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Baden-Wurttemberg
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Germany
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Bayern
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Germany
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Hessen
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Germany
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Niedersachsen
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Germany
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Berlin
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Greece
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Attiki
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Greece
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Thessaloniki
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Hong Kong
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Kowloon City
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Hong Kong
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Hong Kong
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Hong Kong
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Sha Tin
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Israel
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Beer Sheva
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Israel
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Ramat Gan
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Italy
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Campania
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Italy
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Forli-Cesena
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Italy
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Lombardia
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Italy
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Piemonte
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Pordenone
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Italy
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Toscana
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Italy
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Parma
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Italy
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Ravenna
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Aiti
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Ehime
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Hokkaido
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Hukuoka
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Kanagawa
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Japan
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Kumamoto
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Japan
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Miyagi
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Japan
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Okayama
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Japan
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Osaka
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Japan
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Saitama
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Japan
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Tiba
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Tokyo
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Korea, Republic of
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Chungcheongbugdo
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Korea, Republic of
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Busan
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Korea, Republic of
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Goyang
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Korea, Republic of
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Jeongnam
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Korea, Republic of
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Seoul
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Netherlands
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Noord-Holland
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Portugal
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Aveiro
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Portugal
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Porto
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Portugal
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Lisboa
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Russian Federation
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Leningradskaya Oblast
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Russian Federation
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Sankt-Peterburg
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Singapore
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Singapore
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Barcelona
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Cordoba
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Spain
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Madrid
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Spain
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Valencia
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Sweden
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Sodermanlands Lan
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Taiwan
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Dalin
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Taiwan
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Douliu
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Kaohsiung
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Taiwan
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Taichung City
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Taiwan
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Taiwan
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Tainan
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Taiwan
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Taipei
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Turkey
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Adana
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Turkey
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Istanbul
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Turkey
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Izmir
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Turkey
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Sakarya
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Turkey
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Ankara
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Turkey
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Edirne
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Ukraine
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Dnipropetrovs'ka Oblast
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Ukraine
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Kharkivs'ka Oblast
Country [101] 0 0
Ukraine
State/province [101] 0 0
Kropyvnytskyi
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United Kingdom
State/province [102] 0 0
London, City Of
Country [103] 0 0
United Kingdom
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Surrey
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United Kingdom
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Wirral
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United Kingdom
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Leicester
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United Kingdom
State/province [106] 0 0
Manchester

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Takeda
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this study is to compare the effectiveness of TAK-788 as first-line treatment
with that of platinum-based chemotherapy in participants with locally advanced or metastatic
non-small cell lung cancer (NSCLC) whose tumors has epidermal growth factor receptor (EGFR)
exon 20 insertion mutations.

Participants will be randomly assigned to one of the two treatment groups- TAK-788 group or
Platinum-based chemotherapy group.

Participants will receive TAK-788 orally and pemetrexed/cisplatin or pemetrexed/carboplatin
via vein until the participants experience worsening disease (PD) as assessed by blinded
independent review committee (IRC), intolerable harmful effects or another discontinuation
criteria.
Trial website
https://clinicaltrials.gov/ct2/show/NCT04129502
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Study Director
Address 0 0
Takeda
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



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT04129502