Clinical trial NCT04129502: TAK-788 as First-Line Treatment Versus Platinum-Based Chemotherapy for Non-Small Cell Lung Cancer (NSCLC) With EGFR Exon 20 Insertion Mutations
Official 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Advanced/Metastatic Non-Small Cell Lung Cancer (NSCLC)
Keywords: Drug Therapy
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2019-10-16
Enrollment: 354
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to compare 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.

Detailed description: The drug being tested in this study is called TAK-788. TAK-788 is being tested to evaluate the efficacy as a first line treatment compare with platinum-based chemotherapy in the participants with locally advanced or NSCLC whose tumors harbor EGFR exon 20 insertion mutations.

The study will enroll approximately 318 patients. Participants will be randomly assigned to one of the two treatment groups-

* TAK-788 Group (Arm A)
* Platinum-based Chemotherapy Group (Arm B)

The participants will be administered with TAK-788 orally in arm A and pemetrexed/cisplatin or pemetrexed/carboplatin intravenously (IV) in arm B until the participants experience progressive disease (PD) as assessed by blinded independent review committee (IRC), intolerable toxicity or another discontinuation criteria. Participants in the chemotherapy group may cross over to treatment with TAK-788 after IRC-assessed PD is documented. Randomized treatment with TAK-788 or platinum-based chemotherapy may be continued after PD, at the discretion of the investigator and with the sponsor's approval, if there is still evidence of clinical benefit.

This multi-center trial will be conducted in United States (US), Europe, and Asia. The overall time to participate in this study is until 3 years after the last participant is randomized. Participants will make multiple visits to the clinic and will be followed for survival, subsequent anticancer therapy, subsequent disease assessment outcome until disease progression on a subsequent anticancer therapy, and participant-reported health status (EuroQoL-5 Dimensions-5 Levels \[EQ-5D-5L\]) for 3 years after the last participant is randomized in the study and 30 days after the last dose of study drug for safety follow-up.

Eligibility criteria: 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.

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.

Primary outcomes:
measure: Progression Free Survival (PFS) as Assessed by Blinded Independent Review Committee (IRC) per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
timeFrame: Up to approximately 40 months after the first participant is randomized
Secondary outcomes:
measure: Confirmed Objective Response Rate (ORR) as Assessed by Blinded Independent Review Committee (IRC) per RECIST Version 1.1
timeFrame: Up to approximately 40 months after the first participant is randomized
measure: Overall Survival (OS)
timeFrame: Up to approximately 40 months after the first participant is randomized
measure: Progression Free Survival (PFS) as Assessed by the Investigator
timeFrame: Up to approximately 40 months after the first participant is randomized
measure: Confirmed Objective Response Rate (ORR) as Assessed by the Investigator
timeFrame: Up to approximately 40 months after the first participant is randomized
measure: Duration of Response, as Assessed by the Blinded Independent Review Committee (IRC) and the Investigator
timeFrame: Up to approximately 40 months after the first participant is randomized
measure: Time to Response, as Assessed by the Blinded Independent Review Committee (IRC) and the Investigator
timeFrame: Up to approximately 40 months after the first participant is randomized
measure: Disease Control Rate (DCR) as Assessed by the Blinded Independent Review Committee (IRC) and the Investigator
timeFrame: Up to approximately 40 months after the first participant is randomized
measure: 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
timeFrame: Up to approximately 40 months after the first participant is randomized
measure: 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)
timeFrame: Up to approximately 40 months after the first participant is randomized
Other outcomes:
Locations:
city: Long Beach
country: United States
facility: City of Hope National Medical Center
state: California
city: Orange
country: United States
facility: University of California Irvine
state: California
city: Palo Alto
country: United States
facility: Stanford University
state: California
city: Orlando
country: United States
facility: AdventHealth
state: Florida
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Baltimore
country: United States
facility: University of Maryland Greenebaum Cancer Center
state: Maryland
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center - 330 Brookline Ave
state: Massachusetts
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Nashville
country: United States
facility: Sarah Cannon Cancer Center
state: Tennessee
city: Charlottesville
country: United States
facility: University of Virginia Health System
state: Virginia
city: St Leonards
country: Australia
facility: GenesisCare North Shore
state: New South Wales
city: Woolloongabba
country: Australia
facility: Princess Alexandra Hospital
state: Queensland
city: Bedford Park
country: Australia
facility: Flinders Medical Centre
state: South Australia
city: Wien
country: Austria
facility: Klinik Floridsdorf
city: Bruxelles
country: Belgium
facility: Cliniques Universitaires Saint-Luc
state: Brussels
city: Charleroi
country: Belgium
facility: Grand Hopital de Charleroi asbl
state: Hainaut
city: Aalst
country: Belgium
facility: AZ Sint-Lucas
state: Oost-Vlaanderen
city: Vancouver
country: Canada
facility: British Columbia Cancer Agency
state: British Columbia
city: Brampton
country: Canada
facility: William Osler Health System
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Hospital
state: Ontario
city: Montreal
country: Canada
facility: Hopital Du Sacre Coeur de Montreal
state: Quebec
city: Beijing
country: China
facility: Beijing Cancer Hospital - PPDS
state: Beijing
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
state: Henan
city: Changchun
country: China
facility: Jilin Cancer Hospital
state: Jilin
city: Beijing
country: China
facility: Beijing Cancer Hospital - PPDS
city: Beijing
country: China
facility: Beijing Chest Hospital, Capital Medical Univerity
city: Beijing
country: China
facility: Icahn School of Medicine at Mount Sinai
city: Chengdu
country: China
facility: Sichuan Cancer Hospital & Institute
city: Guangzhou
country: China
facility: Guangdong Provincial People's Hospital
city: Hangzhou
country: China
facility: The First Affiliated Hospital, Zhejiang University School of Medicine
city: Harbin
country: China
facility: Harbin Medical University Tumor Hospital
city: Shanghai
country: China
facility: Shanghai East Hospital
city: Wuhan
country: China
facility: Hubei Cancer Hospital
city: Caen
country: France
facility: Centre Francois Baclesse
state: Calvados
city: Nantes
country: France
facility: CHU de Nantes - Hoptal Nord Laennec
state: Loire-Atlantique
city: Lille
country: France
facility: Hopital Calmette
state: Nord
city: Lyon
country: France
facility: Centre Leon Berard
state: Rhone
city: Villejuif
country: France
facility: Institut Gustave Roussy
state: Val-de-Marne
city: Grenoble
country: France
facility: CHU de Grenoble
city: Marseille
country: France
facility: Hopital Nord AP-HM
city: Montpellier
country: France
facility: CRLC Val d'Aurelle - Paul Lamarque
city: Paris
country: France
facility: Hopital Tenon
city: Strasbourg
country: France
facility: Nouvel Hopital Civil
city: Toulouse
country: France
facility: Hopital Larrey
city: Heidelberg
country: Germany
facility: Thoraxklinik-Heidelberg gGmbH
state: Baden-Wurttemberg
city: Munchen
country: Germany
facility: LMU Klinikum der Universitat Munchen
state: Bayern
city: Regensburg
country: Germany
facility: University Clinic Regensburg
state: Bayern
city: Frankfurt am Main
country: Germany
facility: Universitatsklinikum Frankfurt
state: Hessen
city: Oldenburg
country: Germany
facility: Pius Hospital Oldenburg
state: Niedersachsen
city: Berlin
country: Germany
facility: Helios Klinikum Emil Von Behring
city: Athens
country: Greece
facility: Sotiria Chest Hospital of Athens
state: Attiki
city: Thessaloniki
country: Greece
facility: Bioclinic Thessaloniki (Galinos clinic)
city: Kowloon
country: Hong Kong
facility: Princess Margaret Hospital
state: Kowloon City
city: Hong Kong
country: Hong Kong
facility: Pamela Youde Nethersole Eastern Hospital
city: Hong Kong
country: Hong Kong
facility: Queen Elizabeth Hospital (QEH)
city: Hong Kong
country: Hong Kong
facility: Queen Mary Hospital - PPDS
city: Hong Kong
country: Hong Kong
facility: Tuen Mun Hospital
city: Sha Tin
country: Hong Kong
facility: Prince of Wales Hospital
city: Beer Sheva
country: Israel
facility: Soroka University Medical Centre
city: Ramat Gan
country: Israel
facility: Sheba Medical Center - PPDS
city: Napoli
country: Italy
facility: AORN Dei Colli- Ospedale Monaldi Napoli
state: Campania
city: Meldola
country: Italy
facility: Istituto Romagnolo per lo Studio dei Tumori "Dino Amadori" - IRST S.r.l - PPDS
state: Forli-Cesena
city: Milano
country: Italy
facility: Istituto Nazionale Dei Tumori
state: Lombardia
city: Milano
country: Italy
facility: Instituto Europeo Di Oncologia
state: Lombardia
city: Orbassano
country: Italy
facility: Azienda Sanitaria Ospedaliera S Luigi Gonzaga
state: Piemonte
city: Aviano
country: Italy
facility: Centro Di Riferimento Oncologico
state: Pordenone
city: Pisa
country: Italy
facility: Azienda Ospedaliero Universitaria Pisana
state: Toscana
city: Parma
country: Italy
facility: Azienda Ospedaliero Universitaria di Parma
city: Ravenna
country: Italy
facility: Ospedale Santa Maria Delle Croci
city: Toyoake-Shi
country: Japan
facility: Fujita Health University Hospital
state: Aiti
city: Matsuyama-Shi
country: Japan
facility: Ehime University Hospital
state: Ehime
city: Sapporo-Shi
country: Japan
facility: National Hospital Organization Hokkaido Cancer Center
state: Hokkaido
city: Kurume-Shi
country: Japan
facility: Kurume University Hospital
state: Hukuoka
city: Yokohama-Shi
country: Japan
facility: Kanagawa Cancer Center
state: Kanagawa
city: Kumamoto-Shi
country: Japan
facility: Saiseikai Kumamoto Hospital
state: Kumamoto
city: Natori-Shi
country: Japan
facility: Miyagi Cancer Center
state: Miyagi
city: Okayama-Shi
country: Japan
facility: Okayama University Hospital
state: Okayama
city: Chuo Ku
country: Japan
facility: Osaka International Cancer Institute
state: Osaka
city: Komoro
country: Japan
facility: Saitama Cancer Center
state: Saitama
city: Kashiwa-Shi
country: Japan
facility: National Cancer Center Hospital East
state: Tiba
city: Koto-Ku
country: Japan
facility: The Cancer Institute Hospital of Japanese Foundation For Cancer Research
state: Tokyo
city: Cheongju-si
country: Korea, Republic of
facility: Chungbuk National University Hospital
state: Chungcheongbugdo
city: Busan
country: Korea, Republic of
facility: Pusan National University Hospital
city: Goyang
country: Korea, Republic of
facility: National Cancer Center
city: Jeongnam
country: Korea, Republic of
facility: Chonnam National University Hwasun Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center - PPDS
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center PPDS
city: Seoul
country: Korea, Republic of
facility: The Catholic University of Korea, Seoul St. Mary's Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital Yonsei University Health System - PPDS
city: Amsterdam
country: Netherlands
facility: VU Medisch Centrum
state: Noord-Holland
city: Santa Maria Da Feira
country: Portugal
facility: Centro Hospitalar do Porto Hospital de Santo Antonio
state: Aveiro
city: Vila Nova de Gaia
country: Portugal
facility: Hospital Cuf Porto
state: Porto
city: Lisboa
country: Portugal
facility: Centro Hospitalar de Lisboa Norte E.P.E Hospital Pulido Valente
city: Porto
country: Portugal
facility: Instituto Portugues de Oncologia Do Porto Francisco Gentil Epe - PPDS
city: Porto
country: Portugal
facility: Centro Hospitalar de Sao Joao, E.P.E.
city: Saint Petersburg
country: Russian Federation
facility: GBUZ Saint Petersburg Clinical Research Center of Specialized Types of Care (Oncology)
state: Leningradskaya Oblast
city: Saint Petersburg
country: Russian Federation
facility: LLC "EuroCityClinic"
state: Sankt-Peterburg
city: Singapore
country: Singapore
facility: National Cancer Centre
city: L'Hospitalet de Llobregat
country: Spain
facility: ICO lHospitalet Hospital Duran i Reynals
state: Barcelona
city: A Coruna
country: Spain
facility: Hospital Universitario A Coruna
city: Alicante
country: Spain
facility: Hospital General Universitario de Alicante
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebron - PPDS
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona
city: Cordoba
country: Spain
facility: C.H. Regional Reina Sofia - PPDS
city: Madrid
country: Spain
facility: Hospital Universitario Fundacion Jimenez Diaz
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Madrid
country: Spain
facility: Hospital Universitario La Paz - PPDS
city: Valencia
country: Spain
facility: Hospital Universitari i Politecnic La Fe de Valencia
city: Stockholm
country: Sweden
facility: Karolinska Universitetssjukhuset Solna
state: Sodermanlands Lan
city: Dalin
country: Taiwan
facility: Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation
city: Douliu
country: Taiwan
facility: National Taiwan University Hospital - YunLin Branch
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Medical University - Chung-Ho Memorial Hospital
city: Kaohsiung
country: Taiwan
facility: E-DA hospital
city: Taichung City
country: Taiwan
facility: Taichung Veterans General Hospital
city: Tainan City
country: Taiwan
facility: Chi Mei Medical Center, Liouying
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
city: Yuregir
country: Turkey
facility: Baskent University Medical Faculty Adana Practice and Research Center
state: Adana
city: Kadikoy
country: Turkey
facility: T.C. Saglik Bakanligi Goztepe Prof. Dr. Suleyman Yalcin City Hospital
state: Istanbul
city: Bornova
country: Turkey
facility: Ege University Medical Faculty
state: Izmir
city: Karaman
country: Turkey
facility: SAKARYA University Medical Faculty
state: Sakarya
city: Ankara
country: Turkey
facility: Hacettepe University Medical Faculty
city: Edirne
country: Turkey
facility: Trakya University Medical Faculty
city: Dnipropetrovsk
country: Ukraine
facility: Municipal Non-profit Enterprise "City Clinical Hospital # 4" of Dnipro City Council - PPDS
state: Dnipropetrovs'ka Oblast
city: Kharkiv
country: Ukraine
facility: Communal Non-profit Enterprise Regional Center of Oncology
state: Kharkivs'ka Oblast
city: Kropyvnytskyi
country: Ukraine
facility: Private Enterprise Private Manufacturing Company Acinus
city: London
country: United Kingdom
facility: University College London Hospitals (UCLH)
state: London, City Of
city: Sutton
country: United Kingdom
facility: Royal Marsden Hospital - Surrey
state: Surrey
city: Bebington
country: United Kingdom
facility: Clatterbridge Centre For Oncology
state: Wirral
city: Leicester
country: United Kingdom
facility: Leicester General Hospital
city: Manchester
country: United Kingdom
facility: The Christie NHS Foundation Trust - PPDS
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References: