TAK-788 as First-Line Treatment Versus Platinum-Based Chemotherapy for Non-Small Cell Lung Cancer (NSCLC) With EGFR Exon 20 Insertion Mutations

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Advanced/Metastatic Non-Small Cell Lung Cancer (NSCLC)
• Intervention / Treatment: Drug: TAK-788; Drug: Pemetrexed; Drug: Cisplatin; Drug: Carboplatin

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.

• Study Type: Interventional
• Enrollment (Actual): 354
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Kogarah, New South Wales, Australia, 2137
      • St George Hospital
    • St Leonards, New South Wales, Australia, 2065
      • GenesisCare North Shore
  • Queensland
    • Woolloongabba, Queensland, Australia, 4102
      • Princess Alexandra Hospital
  • South Australia
    • Bedford Park, South Australia, Australia, 5042
      • Flinders Medical Centre
  • Tasmania
    • Hobart, Tasmania, Australia, 7000
      • Royal Hobart Hospital
• Austria
  • Graz, Austria, 8036
    • Medizinische Universität Graz
  • Wien, Austria, 1210
    • Klinik Floridsdorf
• Belgium
  • Brussels
    • Bruxelles, Brussels, Belgium, 1200
      • Cliniques Universitaires Saint-Luc
  • Hainaut
    • Charleroi, Hainaut, Belgium, 6000
      • Grand Hopital de Charleroi asbl
  • Oost-Vlaanderen
    • Aalst, Oost-Vlaanderen, Belgium, 9300
      • AZ Sint-Lucas
• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z-4E6
      • British Columbia Cancer Agency
  • Ontario
    • Brampton, Ontario, Canada, L6R 3J7
      • William Osler Health System
    • Toronto, Ontario, Canada, M5G2M9
      • Princess Margaret Hospital
  • Quebec
    • Montreal, Quebec, Canada, H4J 1C5
      • Hopital Du Sacre Coeur de Montreal
• China
  • Beijing, China, 101149
    • Beijing Chest Hospital, Capital Medical Univerity
  • Beijing, China, 100142
    • Beijing Cancer Hospital - PPDS
  • Beijing, China
    • Icahn School of Medicine at Mount Sinai
  • Chengdu, China, 610041
    • Sichuan Cancer Hospital & Institute
  • Guangzhou, China, 510080
    • Guangdong Provincial People'S Hospital
  • Hangzhou, China, 310003
    • The First Affiliated Hospital, Zhejiang University School of Medicine
  • Harbin, China, 150081
    • Harbin Medical University Tumor Hospital
  • Nanchang, China, 330006
    • The Second Affiliated Hospital of Nanchang University
  • Shanghai, China, 200123
    • Shanghai East hospital
  • Wuhan, China, 430079
    • Hubei Cancer Hospital
  • Beijing
    • Beijing, Beijing, China, 100142
      • Beijing Cancer Hospital - PPDS
  • Henan
    • Zhengzhou, Henan, China, 450008
      • Henan Cancer Hospital
  • Jilin
    • Changchun, Jilin, China, 130012
      • Jilin Cancer Hospital
• Denmark
  • Copenhagen, Denmark, 2100
    • Copenhagen University Hospital
  • Odense C, Denmark, DK-5000
    • Odense Universitetshospital
• France
  • Creteil Cedex, France, 94010
    • Centre Hospitalier Intercommunal
  • Grenoble, France, 38043
    • Chu de Grenoble
  • Marseille, France, 13915
    • Hopital Nord AP-HM
  • Montpellier, France, 34298
    • CRLC Val d'Aurelle - Paul Lamarque
  • Paris, France, 75020
    • Hôpital Tenon
  • Rennes, France, 35033
    • Hopital PONTCHAILLOU CHU de Rennes
  • Strasbourg, France, 67091
    • Nouvel Hopital Civil
  • Toulouse, France, 31059
    • Hopital Larrey
  • Calvados
    • Caen, Calvados, France, 14076
      • Centre François Baclesse
  • Loire-Atlantique
    • Nantes, Loire-Atlantique, France, 44000
      • CHU de Nantes - Hoptal Nord Laennec
  • Nord
    • Lille, Nord, France, 59037
      • Hopital Calmette
  • Rhone
    • Bron, Rhone, France, 69500
      • Hopital Louis Pradel
    • Lyon, Rhone, France, 69373
      • Centre Léon Bérard
  • Val-de-Marne
    • Villejuif, Val-de-Marne, France, 94805
      • Institut Gustave Roussy
• Germany
  • Berlin, Germany, 14165
    • Helios Klinikum Emil Von Behring
  • Flensburg, Germany, 24939
    • Malteser Krankenhaus St. Franziskus-Hospital
  • Gauting, Germany, 82131
    • Asklepios Fachkliniken GmbH
  • Baden-Wurttemberg
    • Gerlingen, Baden-Wurttemberg, Germany, 70839
      • Klinik Schillerhohe
    • Heidelberg, Baden-Wurttemberg, Germany, 69126
      • Thoraxklinik-Heidelberg gGmbH
  • Bayern
    • Munchen, Bayern, Germany, 80336
      • LMU Klinikum der Universität München
    • Regensburg, Bayern, Germany, 93053
      • University Clinic Regensburg
  • Hessen
    • Frankfurt am Main, Hessen, Germany, 60596
      • Universitatsklinikum Frankfurt
  • Niedersachsen
    • Oldenburg, Niedersachsen, Germany, 26121
      • Pius Hospital Oldenburg
  • Schleswig-Holstein
    • Kiel, Schleswig-Holstein, Germany, 24116
      • Stadtischen Krankenhaus Kiel
• Greece
  • Thessaloniki, Greece, 546 29
    • Bioclinic Thessaloniki (Galinos Clinic)
  • Attiki
    • Athens, Attiki, Greece, 11527
      • Sotiria Chest Hospital of Athens
    • Piraeus, Attiki, Greece, 185 37
      • Metaxa Cancer Hospital of Piraeus
• Hong Kong
  • Hong Kong, Hong Kong
    • Tuen Mun Hospital
  • Hong Kong, Hong Kong
    • Queen Elizabeth Hospital (QEH)
  • Hong Kong, Hong Kong
    • Pamela Youde Nethersole Eastern Hospital
  • Hong Kong, Hong Kong
    • Queen Mary Hospital - PPDS
  • Sha Tin, Hong Kong
    • Prince of Wales Hospital
  • Kowloon City
    • Kowloon, Kowloon City, Hong Kong
      • Princess Margaret Hospital
• Israel
  • Beer Sheva, Israel, 84101
    • Soroka University Medical Centre
  • Haifa, Israel, 31096
    • Rambam Medical Center PPDS
  • Kfar Saba, Israel, 44281
    • Meir Medical Center
  • Ramat Gan, Israel, 52621
    • Sheba Medical Center - PPDS
• Italy
  • Parma, Italy, 43126
    • Azienda Ospedaliero Universitaria di Parma
  • Ravenna, Italy, 48121
    • Ospedale Santa Maria delle Croci
  • Campania
    • Napoli, Campania, Italy, 80131
      • AORN Dei Colli- Ospedale Monaldi Napoli
  • Forli-Cesena
    • Meldola, Forli-Cesena, Italy, 47014
      • Istituto Romagnolo per lo Studio dei Tumori "Dino Amadori" - IRST S.r.l - PPDS
  • Lombardia
    • Milano, Lombardia, Italy, 20133
      • Istituto Nazionale dei Tumori
    • Milano, Lombardia, Italy, 20141
      • Instituto Europeo di Oncologia
  • Piemonte
    • Orbassano, Piemonte, Italy, 10043
      • Azienda Sanitaria Ospedaliera S Luigi Gonzaga
  • Pordenone
    • Aviano, Pordenone, Italy, 33081
      • Centro di Riferimento Oncologico
  • Sicilia
    • Catania, Sicilia, Italy, 95122
      • Azienda Ospedaliero Universitaria Policlinico Vittorio Emanuele
  • Toscana
    • Pisa, Toscana, Italy, 56124
      • Azienda Ospedaliero Universitaria Pisana
• Japan
  • Aiti
    • Toyoake-Shi, Aiti, Japan, 470-1101
      • Fujita Health University Hospital
  • Ehime
    • Matsuyama-Shi, Ehime, Japan, 791-0280
      • Ehime University Hospital
  • Hirosima
    • Hiroshima-Shi, Hirosima, Japan, 734-0037
      • Hiroshima University Hospital
  • Hokkaido
    • Sapporo-Shi, Hokkaido, Japan, 003-0804
      • National Hospital Organization Hokkaido Cancer Center
  • Hukuoka
    • Kurume-Shi, Hukuoka, Japan, 830-0011
      • Kurume University Hospital
  • Kanagawa
    • Yokohama-Shi, Kanagawa, Japan, 241-0815
      • Kanagawa Cancer Center
  • Kumamoto
    • Kumamoto-Shi, Kumamoto, Japan, 861-4101
      • Saiseikai Kumamoto Hospital
  • Miyagi
    • Natori-Shi, Miyagi, Japan, 981-1239
      • Miyagi Cancer Center
  • Okayama
    • Okayama-Shi, Okayama, Japan, 700-0914
      • Okayama University Hospital
  • Osaka
    • Chuo Ku, Osaka, Japan, 540-0008
      • Osaka International Cancer Institute
    • Osaka-shi, Osaka, Japan, 545-8586
      • Osaka Metropolitan University Hospital
    • Osakasayama-Shi, Osaka, Japan, 589-0014
      • Kindai University Hospital
  • Saitama
    • Komoro, Saitama, Japan, 362-0806
      • Saitama Cancer Center
  • Tiba
    • Kashiwa-Shi, Tiba, Japan, 277-0882
      • National Cancer Center Hospital East
  • Tokyo
    • Koto-Ku, Tokyo, Japan, 135-0063
      • The Cancer Institute Hospital of Japanese Foundation for Cancer Research
  • Yamaguti
    • Ube-Shi, Yamaguti, Japan, 755-0241
      • National Hospital Organization Yamaguchi-Ube Medical Center
• Korea, Republic of
  • Busan, Korea, Republic of, 602-739
    • Pusan National University Hospital
  • Goyang, Korea, Republic of, 410769
    • National Cancer Center
  • Jeongnam, Korea, Republic of, 519-763,
    • Chonnam National University Hwasun Hospital
  • Seoul, Korea, Republic of, 03080
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 02841
    • Korea University Anam Hospital
  • Seoul, Korea, Republic of, 06591
    • The Catholic University of Korea, Seoul St. Mary's Hospital
  • Seoul, Korea, Republic of, 05505
    • Asan Medical Center - PPDS
  • Seoul, Korea, Republic of, 06351
    • Samsung Medical Center PPDS
  • Seoul, Korea, Republic of, 120-752
    • Severance Hospital Yonsei University Health System - PPDS
  • Chungcheongbugdo
    • Cheongju-si, Chungcheongbugdo, Korea, Republic of, 28644
      • Chungbuk National University Hospital
• Netherlands
  • Noord-Holland
    • Amsterdam, Noord-Holland, Netherlands, 1081 HV
      • VU Medisch Centrum
• Portugal
  • Lisboa, Portugal, 1400-038
    • Fundação Champalimaud
  • Lisboa, Portugal, 1769-001
    • Centro Hospitalar de Lisboa Norte E.P.E Hospital Pulido Valente
  • Porto, Portugal, 4200-072
    • Instituto Portugues de Oncologia Do Porto Francisco Gentil Epe - PPDS
  • Porto, Portugal, 4200
    • Centro Hospitalar de São João, E.P.E.
  • Aveiro
    • Santa Maria Da Feira, Aveiro, Portugal, 4520-211
      • Centro Hospitalar do Porto Hospital de Santo Antonio
  • Porto
    • Vila Nova de Gaia, Porto, Portugal, 4434-502
      • Hospital CUF Porto
• Russian Federation
  • Moscow, Russian Federation, 143423
    • Moscow City Oncology Hospital #62
  • St. Petersburg, Russian Federation, 197758
    • Scientific Research Institute of Oncology n.a. N.N. Petrov
  • Leningradskaya Oblast
    • Saint Petersburg, Leningradskaya Oblast, Russian Federation, 197758
      • GBUZ Saint Petersburg Clinical Research Center of Specialized Types of Care (Oncology)
  • Sankt-Peterburg
    • Saint Petersburg, Sankt-Peterburg, Russian Federation, 197022
      • LLC "Eurocityclinic"
• Singapore
  • Singapore, Singapore, 169608
    • National Cancer Centre
• Spain
  • A Coruna, Spain, 15006
    • Hospital Universitario A Coruña
  • Alicante, Spain, 03010
    • Hospital General Universitario de Alicante
  • Barcelona, Spain, 08036
    • Hospital Clinic de Barcelona
  • Barcelona, Spain, 08035
    • Hospital Universitario Vall d'Hebron - PPDS
  • Cordoba, Spain, 14004
    • C.H. Regional Reina Sofia - PPDS
  • Madrid, Spain, 28040
    • Hospital Universitario Fundacion Jimenez Diaz
  • Madrid, Spain, 28041
    • Hospital Universitario 12 De Octubre
  • Madrid, Spain, 28007
    • Hospital General Universitario Gregorio Maranon
  • Madrid, Spain, 28046
    • Hospital Universitario La Paz - PPDS
  • Malaga, Spain, 29010
    • Hospital Regional Universitario de Malaga Hospital General
  • Sevilla, Spain, 41013
    • Hospital Universitario Virgen del Rocio - PPDS
  • Valencia, Spain, 46026
    • Hospital Universitari i Politecnic La Fe de Valencia
  • Barcelona
    • L'Hospitalet de Llobregat, Barcelona, Spain, 08907
      • ICO lHospitalet Hospital Duran i Reynals
  • Madrid
    • Majadahonda, Madrid, Spain, 28222
      • Hospital Universitario Puerta de Hierro - Majadahonda
• Sweden
  • Sodermanlands Lan
    • Stockholm, Sodermanlands Lan, Sweden
      • Karolinska Universitetssjukhuset Solna
  • Vastra Gotalands Lan
    • Goteborg, Vastra Gotalands Lan, Sweden, 413 45
      • Sahlgrenska Universitetssjukhuset
• Switzerland
  • Winterthur, Switzerland, 8401
    • Kantonsspital Winterthur
  • Basel-Stadt (de)
    • Basel, Basel-Stadt (de), Switzerland, 4031
      • Universitätsspital Basel
• Taiwan
  • Dalin, Taiwan, 622
    • Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation
  • Douliu, Taiwan, 640
    • National Taiwan University Hospital - YunLin Branch
  • Kaohsiung, Taiwan, 82445
    • E-DA hospital
  • Kaohsiung, Taiwan, 807
    • Kaohsiung Medical University - Chung-Ho Memorial Hospital
  • Taichung City, Taiwan, 407
    • Taichung Veterans General Hospital
  • Tainan, Taiwan, 704
    • National Cheng Kung University Hospital
  • Tainan City, Taiwan, 736
    • Chi Mei Medical Center, Liouying
  • Taipei, Taiwan, 10002
    • National Taiwan University Hospital
  • Taipei, Taiwan, 112
    • Taipei Veterans General Hospital
• Turkey
  • Ankara, Turkey, 06100
    • Hacettepe University Medical Faculty
  • Edirne, Turkey, 22030
    • Trakya University Medical Faculty
  • Adana
    • Yuregir, Adana, Turkey, 01120
      • Baskent University Medical Faculty Adana Practice and Research Center
  • Istanbul
    • Fatih, Istanbul, Turkey, 34098
      • Istanbul University Cerrahpasa Medical Faculty Hospital
    • Kadikoy, Istanbul, Turkey, 34772
      • T.C. Saglik Bakanligi Goztepe Prof. Dr. Suleyman Yalcin City Hospital
  • Izmir
    • Bornova, Izmir, Turkey, 35100
      • Ege University Medical Faculty
  • Kocaeli
    • Izmit, Kocaeli, Turkey, 41380
      • Kocaeli University Hospital
  • Sakarya
    • Karaman, Sakarya, Turkey, 54290
      • SAKARYA University Medical Faculty
• Ukraine
  • Kropyvnytskyi, Ukraine, 25006
    • Private Enterprise Private Manufacturing Company Acinus
  • Dnipropetrovs'ka Oblast
    • Dnipropetrovsk, Dnipropetrovs'ka Oblast, Ukraine, 49102
      • Municipal Non-profit Enterprise "City Clinical Hospital # 4" of Dnipro City Council - PPDS
  • Ivano-Frankivs'ka Oblast
    • Ivano-Frankivsk, Ivano-Frankivs'ka Oblast, Ukraine, 76018
      • Municipal Non-profit Enterprise SubCarpathian Clinical Oncological Centre of Ivano-Frankivsk RC
  • Kharkivs'ka Oblast
    • Kharkiv, Kharkivs'ka Oblast, Ukraine, 61070
      • Communal Non-profit Enterprise Regional Center of Oncology
• United Kingdom
  • Leicester, United Kingdom, LE1 5WW
    • Leicester General Hospital
  • Manchester, United Kingdom, M20 4GJ
    • The Christie NHS Foundation Trust - PPDS
  • Cardiff
    • Whitchurch, Cardiff, United Kingdom, CF14 2TL
      • Velindre Cancer Centre - PPDS
  • London, City Of
    • London, London, City Of, United Kingdom, NW1 2PG
      • University College London Hospitals (UCLH)
    • London, London, City Of, United Kingdom, SW3 6JJ
      • The Royal Marsden - London
  • Surrey
    • Sutton, Surrey, United Kingdom, SM2 5PT
      • Royal Marsden Hospital - Surrey
  • Wirral
    • Bebington, Wirral, United Kingdom, CH63 4JY
      • Clatterbridge Centre for Oncology
• United States
  • California
    • La Jolla, California, United States, 92093
      • UC San Diego Moores Cancer Center
    • Long Beach, California, United States, 90813
      • City of Hope National Medical Center
    • Los Angeles, California, United States, 90027
      • California Research Institute
    • Orange, California, United States, 92868
      • University of California Irvine
    • Palo Alto, California, United States, 94304
      • Stanford University
  • Connecticut
    • Norwich, Connecticut, United States, 06360
      • Eastern CT Hematology and Oncology Associates
  • Florida
    • Orlando, Florida, United States, 32804
      • AdventHealth
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland Greenebaum Cancer Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Dana Farber Cancer Institute
    • Boston, Massachusetts, United States, 02115
      • Massachusetts General Hospital
    • Boston, Massachusetts, United States, 02115
      • Beth Israel Deaconess Medical Center - 330 Brookline Ave
  • New York
    • New York, New York, United States, 10029
      • Icahn School of Medicine at Mount Sinai
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19111
      • Fox Chase Cancer Center
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Cancer Center
  • Texas
    • Dallas, Texas, United States, 75246
      • Texas Oncology-Baylor Charles A. Sammons Cancer Center - USOR
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia Health System

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.	Drug: TAK-788; TAK-788 capsule; Other Names: AP32788; Mobocertinib
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.	Drug: Pemetrexed; Pemetrexed IV infusion; Other Names: Alimta; Drug: Cisplatin; Cisplatin IV infusion; Drug: Carboplatin; Carboplatin IV infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 progressive disease (PD) according to RECIST Version 1.1 are met or death, whichever occurs first.	Up to approximately 40 months after the first participant is randomized

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Confirmed Objective Response Rate (ORR) as Assessed by Blinded Independent Review Committee (IRC) per RECIST Version 1.1	Confirmed ORR is defined as the percentage 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.	Up to approximately 40 months after the first participant is randomized
Overall Survival (OS)	OS is defined as the interval from the date of randomization until death.	Up to approximately 40 months after the first participant is randomized
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 PD according to RECIST Version 1.1 are met or death, whichever occurs first.	Up to approximately 40 months after the first participant is randomized
Confirmed Objective Response Rate (ORR) as Assessed by the Investigator	Confirmed ORR is defined as the percentage 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.	Up to approximately 40 months after the first participant is randomized
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 or death (whichever occurs first) is objectively documented.	Up to approximately 40 months after the first participant is randomized
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.	Up to approximately 40 months after the first participant is randomized
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.	Up to approximately 40 months after the first participant is randomized
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).	Up to approximately 40 months after the first participant is randomized
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.	Up to approximately 40 months after the first participant is randomized

Collaborators and Investigators

• Sponsor: Takeda
• Investigators: Study Director: Study Director, Takeda

Study record dates

Study Major Dates

• Study Start (Actual): January 10, 2020
• Primary Completion (Estimated): February 20, 2026
• Study Completion (Estimated): June 12, 2026

Study Registration Dates

• First Submitted: October 7, 2019
• First Submitted That Met QC Criteria: October 15, 2019
• First Posted (Actual): October 16, 2019

Study Record Updates

• Last Update Posted (Actual): April 11, 2024
• Last Update Submitted That Met QC Criteria: April 10, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Drug Therapy
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Folic Acid Antagonists; Tyrosine Kinase Inhibitors; Carboplatin; Pemetrexed; Mobocertinib
• Other Study ID Numbers: TAK-788-3001; NL20191212 (Registry Identifier: CCMO); 2019-001845-42 (Registry Identifier: EudraCT); U1111-1232-6059 (Other Grant/Funding Number: WHO); jRCT2071210098 (Registry Identifier: jRCT)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
• IPD Sharing Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No