We are experiencing 4 week turn-around time in review of submissions and resubmissions. We recommend commencing this process concurrently with your ethics submission and allowing at least 8 weeks for registration to be completed from date of first submission. We currently do not have the capacity to expedite reviews.

Note also there are delays to review of updates. We appreciate your patience.

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
Trial details imported from ClinicalTrials.gov

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




Registration number
NCT04129502
Ethics application status
Date submitted
7/10/2019
Date registered
16/10/2019
Date last updated
29/01/2021

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 mg, capsules, orally, once daily until the participants experience progressive disease (PD) as assessed by blinded independent review committee (IRC), intolerable toxicity, or another discontinuation criteria.

Active Comparator: Platinum-based Chemotherapy Group (Arm B) - Pemetrexed 500 mg/m^2 plus Cisplatin 75 mg/m^2, infusion, intravenously, once on Day 1 of 21-day cycle pemetrexed 500 mg/m^2 plus Carboplatin, infusion, intravenously, once at a dose calculated to produce area under curve (AUC) of 5 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 - PFS is defined as the time interval from the date of randomization until the first date at which the criteria for PD according to RECIST version 1.1 are met or death, whichever occurs first.
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 - Confirmed ORR is defined as the proportion of participants who are confirmed to have achieved complete response (CR) or partial response (PR). Confirmed responses are responses that persist on repeat imaging =4 weeks after initial response.
Timepoint [1] 0 0
Up to approximately 40 months after the first participant is randomized
Secondary outcome [2] 0 0
Overall Survival (OS) - OS is defined as the interval from the date of randomization until death.
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 - PFS is defined as the time interval from the date of randomization until the first date at which the criteria for progressive disease (PD) according to RECIST version 1.1 are met or death, whichever occurs first.
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 - Confirmed ORR is defined as the proportion of participants who are confirmed to have achieved CR or PR. Confirmed responses are responses that persist on repeat imaging =4 weeks after initial response.
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 - Duration of response is defined as the time interval from the time that the measurement criteria are first met for CR/PR (whichever is first recorded) until the first date that PD is objectively documented.
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 - Time to response is defined as the time interval from the date of randomization until the initial observation of CR or PR.
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 - DCR is defined as the percentage of participants who have achieved CR, PR, or stable disease (SD) (in the case of SD, measurements must have met the SD criteria at least once after study entry at a minimum interval of 6 weeks) after the initiation of study drug.
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 - EORTC QLQ-C30 is a cancer-specific questionnaire which comprises of 5 functional scales (physical, role, cognitive, emotional, and social functioning); 3 symptom scales (fatigue, pain, and nausea/vomiting); and a global health status/quality-of-life (QoL) scale. Six single-item scales are also included (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Raw scores will be converted into scale scores ranging from 0 to 100. For the functional scales and the global health status/QoL scale, higher scores represent better HRQoL, whereas for the symptom scales lower scores represent better HRQoL (i.e., a low level of symptomatology/problems).
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) - EORTC QLQ-LC13 is a cancer-specific questionnaire which comprises of 13 questions assessing lung cancer-associated symptoms (cough, hemoptysis, dyspnea, and site-specific pain), treatment-related side effects (sore mouth, dysphagia, peripheral neuropathy, and alopecia), and use of pain medication. Raw scores will be converted into scale scores ranging from 0 to 100. Higher scores represent a high level of symptomatology/problems.
Timepoint [9] 0 0
Up to approximately 40 months after the first participant is randomized

Eligibility
Key inclusion criteria
- Histologically or cytologically confirmed nonsquamous cell locally advanced not
suitable for definitive therapy, recurrent, or metastatic (Stage IV) non-small cell
lung cancer (NSCLC)

- Documented epithelial growth factor receptor (EGFR) in-frame exon 20 insertion
mutation assessed by a clinical laboratory improvements amendment (CLIA)-certified
(United States [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 HER2 mutations except EGFR mutations for which there are approved anti-EGFR 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 response evaluation criteria in solid tumors (RECIST)
version 1.1

- Life expectancy =3 months

- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Received prior systemic treatment for locally advanced or metastatic disease

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

- Received a moderate or strong cytochrome P-450 (CYP)3A inhibitor or moderate or strong
CYP3A inducer within 10 days before randomization

- 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

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
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,TAS
Recruitment hospital [1] 0 0
St George Hospital - Kogarah
Recruitment hospital [2] 0 0
Northern Cancer Institute, St Leonards - St Leonards
Recruitment hospital [3] 0 0
Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [4] 0 0
Flinders Medical Centre - Bedford Park
Recruitment hospital [5] 0 0
Royal Hobart Hospital - Hobart
Recruitment postcode(s) [1] 0 0
2137 - Kogarah
Recruitment postcode(s) [2] 0 0
2065 - St Leonards
Recruitment postcode(s) [3] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [4] 0 0
5042 - Bedford Park
Recruitment postcode(s) [5] 0 0
7000 - Hobart
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Connecticut
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Hawaii
Country [6] 0 0
United States of America
State/province [6] 0 0
Illinois
Country [7] 0 0
United States of America
State/province [7] 0 0
Maryland
Country [8] 0 0
United States of America
State/province [8] 0 0
Massachusetts
Country [9] 0 0
United States of America
State/province [9] 0 0
New York
Country [10] 0 0
United States of America
State/province [10] 0 0
North Carolina
Country [11] 0 0
United States of America
State/province [11] 0 0
Pennsylvania
Country [12] 0 0
United States of America
State/province [12] 0 0
Tennessee
Country [13] 0 0
United States of America
State/province [13] 0 0
Texas
Country [14] 0 0
United States of America
State/province [14] 0 0
Virginia
Country [15] 0 0
United States of America
State/province [15] 0 0
Washington
Country [16] 0 0
Austria
State/province [16] 0 0
Graz
Country [17] 0 0
Austria
State/province [17] 0 0
Wien
Country [18] 0 0
Belgium
State/province [18] 0 0
Brussels
Country [19] 0 0
Belgium
State/province [19] 0 0
Hainaut
Country [20] 0 0
Belgium
State/province [20] 0 0
Gent
Country [21] 0 0
Canada
State/province [21] 0 0
Alberta
Country [22] 0 0
Canada
State/province [22] 0 0
British Columbia
Country [23] 0 0
Canada
State/province [23] 0 0
Ontario
Country [24] 0 0
Canada
State/province [24] 0 0
Quebec
Country [25] 0 0
China
State/province [25] 0 0
Beijing
Country [26] 0 0
China
State/province [26] 0 0
Guangzhou
Country [27] 0 0
China
State/province [27] 0 0
Henan
Country [28] 0 0
China
State/province [28] 0 0
Changchun
Country [29] 0 0
China
State/province [29] 0 0
Chengdu
Country [30] 0 0
China
State/province [30] 0 0
Hangzhou
Country [31] 0 0
China
State/province [31] 0 0
Harbin
Country [32] 0 0
China
State/province [32] 0 0
Nanchang
Country [33] 0 0
China
State/province [33] 0 0
Shanghai
Country [34] 0 0
China
State/province [34] 0 0
Wuhan
Country [35] 0 0
Denmark
State/province [35] 0 0
Nordjylland
Country [36] 0 0
Denmark
State/province [36] 0 0
Copenhagen
Country [37] 0 0
Denmark
State/province [37] 0 0
Odense C
Country [38] 0 0
France
State/province [38] 0 0
Calvados
Country [39] 0 0
France
State/province [39] 0 0
Loire-Atlantique
Country [40] 0 0
France
State/province [40] 0 0
Nord
Country [41] 0 0
France
State/province [41] 0 0
Rhone
Country [42] 0 0
France
State/province [42] 0 0
Val-de-Marne
Country [43] 0 0
France
State/province [43] 0 0
Creteil Cedex
Country [44] 0 0
France
State/province [44] 0 0
Grenoble
Country [45] 0 0
France
State/province [45] 0 0
Marseille
Country [46] 0 0
France
State/province [46] 0 0
Montpellier
Country [47] 0 0
France
State/province [47] 0 0
Paris
Country [48] 0 0
France
State/province [48] 0 0
Rennes
Country [49] 0 0
France
State/province [49] 0 0
Strasbourg
Country [50] 0 0
France
State/province [50] 0 0
Toulouse
Country [51] 0 0
Germany
State/province [51] 0 0
Baden-Wurttemberg
Country [52] 0 0
Germany
State/province [52] 0 0
Bayern
Country [53] 0 0
Germany
State/province [53] 0 0
Hessen
Country [54] 0 0
Germany
State/province [54] 0 0
Niedersachsen
Country [55] 0 0
Germany
State/province [55] 0 0
Schleswig-Holstein
Country [56] 0 0
Germany
State/province [56] 0 0
Berlin
Country [57] 0 0
Germany
State/province [57] 0 0
Flensburg
Country [58] 0 0
Germany
State/province [58] 0 0
Gauting
Country [59] 0 0
Germany
State/province [59] 0 0
Grosshansdorf
Country [60] 0 0
Germany
State/province [60] 0 0
Koln
Country [61] 0 0
Greece
State/province [61] 0 0
Attiki
Country [62] 0 0
Greece
State/province [62] 0 0
Thessaloniki
Country [63] 0 0
Hong Kong
State/province [63] 0 0
Kowloon City
Country [64] 0 0
Hong Kong
State/province [64] 0 0
Hong Kong
Country [65] 0 0
Hong Kong
State/province [65] 0 0
Sha Tin
Country [66] 0 0
Israel
State/province [66] 0 0
Beer Sheva
Country [67] 0 0
Israel
State/province [67] 0 0
Haifa
Country [68] 0 0
Israel
State/province [68] 0 0
Kfar Saba
Country [69] 0 0
Israel
State/province [69] 0 0
Ramat Gan
Country [70] 0 0
Italy
State/province [70] 0 0
Campania
Country [71] 0 0
Italy
State/province [71] 0 0
Emilia-Romagna
Country [72] 0 0
Italy
State/province [72] 0 0
Forli-Cesena
Country [73] 0 0
Italy
State/province [73] 0 0
Lombardia
Country [74] 0 0
Italy
State/province [74] 0 0
Piemonte
Country [75] 0 0
Italy
State/province [75] 0 0
Pordenone
Country [76] 0 0
Italy
State/province [76] 0 0
Sicilia
Country [77] 0 0
Italy
State/province [77] 0 0
Milano
Country [78] 0 0
Italy
State/province [78] 0 0
Parma
Country [79] 0 0
Italy
State/province [79] 0 0
Pisa
Country [80] 0 0
Korea, Republic of
State/province [80] 0 0
Jeollanam-do
Country [81] 0 0
Korea, Republic of
State/province [81] 0 0
Busan
Country [82] 0 0
Korea, Republic of
State/province [82] 0 0
Cheongju-si
Country [83] 0 0
Korea, Republic of
State/province [83] 0 0
Goyang
Country [84] 0 0
Korea, Republic of
State/province [84] 0 0
Seoul
Country [85] 0 0
Netherlands
State/province [85] 0 0
Noord-Holland
Country [86] 0 0
Portugal
State/province [86] 0 0
Aveiro
Country [87] 0 0
Portugal
State/province [87] 0 0
Lisboa
Country [88] 0 0
Portugal
State/province [88] 0 0
Porto
Country [89] 0 0
Russian Federation
State/province [89] 0 0
Leningradskaya Oblast
Country [90] 0 0
Russian Federation
State/province [90] 0 0
Moscow
Country [91] 0 0
Russian Federation
State/province [91] 0 0
Saint Petersburg
Country [92] 0 0
Russian Federation
State/province [92] 0 0
St. Petersburg
Country [93] 0 0
Singapore
State/province [93] 0 0
Singapore
Country [94] 0 0
Spain
State/province [94] 0 0
Barcelona
Country [95] 0 0
Spain
State/province [95] 0 0
A Coruna
Country [96] 0 0
Spain
State/province [96] 0 0
Alicante
Country [97] 0 0
Spain
State/province [97] 0 0
Cordoba
Country [98] 0 0
Spain
State/province [98] 0 0
Madrid
Country [99] 0 0
Spain
State/province [99] 0 0
Majadahonda
Country [100] 0 0
Spain
State/province [100] 0 0
Malaga
Country [101] 0 0
Spain
State/province [101] 0 0
Sevilla
Country [102] 0 0
Spain
State/province [102] 0 0
Valencia
Country [103] 0 0
Sweden
State/province [103] 0 0
Sodermanlands Lan
Country [104] 0 0
Sweden
State/province [104] 0 0
Goteborg
Country [105] 0 0
Switzerland
State/province [105] 0 0
Basel-Stadt (de)
Country [106] 0 0
Switzerland
State/province [106] 0 0
Vaud (fr)
Country [107] 0 0
Switzerland
State/province [107] 0 0
Winterthur
Country [108] 0 0
Taiwan
State/province [108] 0 0
Chiayi
Country [109] 0 0
Taiwan
State/province [109] 0 0
Douliu
Country [110] 0 0
Taiwan
State/province [110] 0 0
Kaohsiung
Country [111] 0 0
Taiwan
State/province [111] 0 0
Taichung City
Country [112] 0 0
Taiwan
State/province [112] 0 0
Tainan City
Country [113] 0 0
Taiwan
State/province [113] 0 0
Tainan
Country [114] 0 0
Taiwan
State/province [114] 0 0
Taipei
Country [115] 0 0
Turkey
State/province [115] 0 0
Adana
Country [116] 0 0
Turkey
State/province [116] 0 0
Istanbul
Country [117] 0 0
Turkey
State/province [117] 0 0
Izmir
Country [118] 0 0
Turkey
State/province [118] 0 0
Kocaeli
Country [119] 0 0
Turkey
State/province [119] 0 0
Sakarya
Country [120] 0 0
Turkey
State/province [120] 0 0
Ankara
Country [121] 0 0
Turkey
State/province [121] 0 0
Edirne
Country [122] 0 0
Ukraine
State/province [122] 0 0
Dnipropetrovs'ka Oblast
Country [123] 0 0
Ukraine
State/province [123] 0 0
Ivano-Frankivsk
Country [124] 0 0
Ukraine
State/province [124] 0 0
Kharkiv
Country [125] 0 0
Ukraine
State/province [125] 0 0
Kropyvnytskyi
Country [126] 0 0
United Kingdom
State/province [126] 0 0
Cardiff
Country [127] 0 0
United Kingdom
State/province [127] 0 0
London, City Of
Country [128] 0 0
United Kingdom
State/province [128] 0 0
Wirral
Country [129] 0 0
United Kingdom
State/province [129] 0 0
Leicester
Country [130] 0 0
United Kingdom
State/province [130] 0 0
Manchester

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Millennium Pharmaceuticals, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this study is to compare the efficacy 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 harbor epidermal growth factor receptor
(EGFR) exon 20 insertion mutations.
Trial website
https://clinicaltrials.gov/show/NCT04129502
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Medical Director
Address 0 0
Millennium Pharmaceuticals, Inc.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Takeda Study Registration Call Center
Address 0 0
Country 0 0
Phone 0 0
1-877-825-3327
Fax 0 0
Email 0 0
medinfoUS@takeda.com
Contact person for scientific queries

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