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

NCT04129502 | Active Not Recruiting Phase 3 DMC FDA Drug

• 5 other identifiers: TAK-788-3001NL201912122019-001845-42U1111-1232-6059jRCT2071210098
• Study Type: interventional
• Target: 354
• Locations: 23 countries
• Sites: 133

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.

Conditions

Advanced/Metastatic Non-Small Cell Lung Cancer (NSCLC)

Keywords

Drug Therapy

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (9)

• Confirmed Objective Response Rate (ORR) as Assessed by Blinded Independent Review Committee (IRC) per RECIST Version 1.1

  Up to approximately 40 months after the first participant is randomized

• Overall Survival (OS)

  Up to approximately 40 months after the first participant is randomized

• Progression Free Survival (PFS) as Assessed by the Investigator

  Up to approximately 40 months after the first participant is randomized

• Confirmed Objective Response Rate (ORR) as Assessed by the Investigator

  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

  Up to approximately 40 months after the first participant is randomized

Study Arms (2)

TAK-788 Group (Arm A)

EXPERIMENTAL

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

Platinum-based Chemotherapy Group (Arm B)

ACTIVE COMPARATOR

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; Drug: Cisplatin; Drug: Carboplatin

Interventions

TAK-788 DRUG

TAK-788 capsule

Also known as: AP32788, Mobocertinib

TAK-788 Group (Arm A)

Pemetrexed DRUG

Pemetrexed IV infusion

Also known as: Alimta

Platinum-based Chemotherapy Group (Arm B)

Cisplatin DRUG

Cisplatin IV infusion

Platinum-based Chemotherapy Group (Arm B)

Carboplatin DRUG

Carboplatin IV infusion

Platinum-based Chemotherapy Group (Arm B)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Takeda: lead

Study Sites (134)

City of Hope National Medical Center

Long Beach, California, 90813, United States

Location

University of California Irvine

Orange, California, 92868, United States

Location

Stanford University

Palo Alto, California, 94304, United States

Location

AdventHealth

Orlando, Florida, 32804, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

University of Maryland Greenebaum Cancer Center

Baltimore, Maryland, 21201, United States

Location

Beth Israel Deaconess Medical Center - 330 Brookline Ave

Boston, Massachusetts, 02115, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02115, United States

Location

Sarah Cannon Cancer Center

Nashville, Tennessee, 37203, United States

Location

University of Virginia Health System

Charlottesville, Virginia, 22908, United States

Location

GenesisCare North Shore

St Leonards, New South Wales, 2065, Australia

Location

Princess Alexandra Hospital

Woolloongabba, Queensland, 4102, Australia

Location

Flinders Medical Centre

Bedford Park, South Australia, 5042, Australia

Location

Klinik Floridsdorf

Vienna, 1210, Austria

Location

Cliniques Universitaires Saint-Luc

Brussels, Brussels Capital, 1200, Belgium

Location

Grand Hopital de Charleroi asbl

Charleroi, Hainaut, 6000, Belgium

Location

AZ Sint-Lucas

Aalst, Oost-Vlaanderen, 9300, Belgium

Location

British Columbia Cancer Agency

Vancouver, British Columbia, V5Z-4E6, Canada

Location

William Osler Health System

Brampton, Ontario, L6R 3J7, Canada

Location

Princess Margaret Hospital

Toronto, Ontario, M5G2M9, Canada

Location

Hopital Du Sacre Coeur de Montreal

Montreal, Quebec, H4J 1C5, Canada

Location

Beijing Cancer Hospital - PPDS

Beijing, Beijing Municipality, 100142, China

Location

Henan Cancer Hospital

Zhengzhou, Henan, 450008, China

Location

Jilin Cancer Hospital

Changchun, Jilin, 130012, China

Location

Beijing Cancer Hospital - PPDS

Beijing, 100142, China

Location

Beijing Chest Hospital, Capital Medical Univerity

Beijing, 101149, China

Location

Icahn School of Medicine at Mount Sinai

Beijing, China

Location

Sichuan Cancer Hospital & Institute

Chengdu, 610041, China

Location

Guangdong Provincial People's Hospital

Guangzhou, 510080, China

Location

The First Affiliated Hospital, Zhejiang University School of Medicine

Hangzhou, 310003, China

Location

Harbin Medical University Tumor Hospital

Harbin, 150081, China

Location

Shanghai East Hospital

Shanghai, 200123, China

Location

Hubei Cancer Hospital

Wuhan, 430079, China

Location

Centre Francois Baclesse

Caen, Calvados, 14076, France

Location

CHU de Nantes - Hoptal Nord Laennec

Nantes, Loire-Atlantique, 44000, France

Location

Hopital Calmette

Lille, Nord, 59037, France

Location

Centre Leon Berard

Lyon, Rhone, 69373, France

Location

Institut Gustave Roussy

Villejuif, Val-de-Marne, 94805, France

Location

CHU de Grenoble

Grenoble, 38043, France

Location

Hopital Nord AP-HM

Marseille, 13915, France

Location

CRLC Val d'Aurelle - Paul Lamarque

Montpellier, 34298, France

Location

Hopital Tenon

Paris, 75020, France

Location

Nouvel Hopital Civil

Strasbourg, 67091, France

Location

Hopital Larrey

Toulouse, 31059, France

Location

Thoraxklinik-Heidelberg gGmbH

Heidelberg, Baden-Wurttemberg, 69126, Germany

Location

LMU Klinikum der Universitat Munchen

München, Bavaria, 80336, Germany

Location

University Clinic Regensburg

Regensburg, Bavaria, 93053, Germany

Location

Universitatsklinikum Frankfurt

Frankfurt am Main, Hesse, 60596, Germany

Location

Pius Hospital Oldenburg

Oldenburg, Lower Saxony, 26121, Germany

Location

Helios Klinikum Emil Von Behring

Berlin, 14165, Germany

Location

Sotiria Chest Hospital of Athens

Athens, Attica, 11527, Greece

Location

Bioclinic Thessaloniki (Galinos clinic)

Thessaloniki, 546 29, Greece

Location

Princess Margaret Hospital

Kowloon City, Kowloon City, Hong Kong

Location

Pamela Youde Nethersole Eastern Hospital

Hong Kong, Hong Kong

Location

Queen Elizabeth Hospital (QEH)

Hong Kong, Hong Kong

Location

Queen Mary Hospital - PPDS

Hong Kong, Hong Kong

Location

Tuen Mun Hospital

Hong Kong, Hong Kong

Location

Prince of Wales Hospital

Shatin, Hong Kong

Location

Soroka University Medical Centre

Beersheba, 84101, Israel

Location

Sheba Medical Center - PPDS

Ramat Gan, 52621, Israel

Location

AORN Dei Colli- Ospedale Monaldi Napoli

Naples, Campania, 80131, Italy

Location

Istituto Romagnolo per lo Studio dei Tumori "Dino Amadori" - IRST S.r.l - PPDS

Meldola, Forli-Cesena, 47014, Italy

Location

Istituto Nazionale Dei Tumori

Milan, Lombardy, 20133, Italy

Location

Instituto Europeo Di Oncologia

Milan, Lombardy, 20141, Italy

Location

Azienda Sanitaria Ospedaliera S Luigi Gonzaga

Orbassano, Piedmont, 10043, Italy

Location

Centro Di Riferimento Oncologico

Aviano, Pordenone, 33081, Italy

Location

Azienda Ospedaliero Universitaria Pisana

Pisa, Tuscany, 56124, Italy

Location

Azienda Ospedaliero Universitaria di Parma

Parma, 43126, Italy

Location

Ospedale Santa Maria Delle Croci

Ravenna, 48121, Italy

Location

Fujita Health University Hospital

Toyoake-Shi, Aiti, 470-1101, Japan

Location

National Cancer Center Hospital East

Kashiwa-Shi, Chiba, 277-0882, Japan

Location

Ehime University Hospital

Matsuyama, Ehime, 791-0280, Japan

Location

National Hospital Organization Hokkaido Cancer Center

Sapporo, Hokkaido, 003-0804, Japan

Location

Kurume University Hospital

Kurume-Shi, Hukuoka, 830-0011, Japan

Location

Kanagawa Cancer Center

Yokohama, Kanagawa, 241-0815, Japan

Location

Saiseikai Kumamoto Hospital

Kumamoto, Kumamoto, 861-4101, Japan

Location

Miyagi Cancer Center

Natori-shi, Miyagi, 981-1239, Japan

Location

Okayama University Hospital

Okayama, Okayama-ken, 700-0914, Japan

Location

Osaka International Cancer Institute

Chuo Ku, Osaka, 540-0008, Japan

Location

Saitama Cancer Center

Komoro, Saitama, 362-0806, Japan

Location

The Cancer Institute Hospital of Japanese Foundation For Cancer Research

Koto-Ku, Tokyo, 135-0063, Japan

Location

VU Medisch Centrum

Amsterdam, North Holland, 1081 HV, Netherlands

Location

Centro Hospitalar do Porto Hospital de Santo Antonio

Santa Maria da Feira, Aveiro District, 4520-211, Portugal

Location

Hospital Cuf Porto

Vila Nova de Gaia, Porto District, 4434-502, Portugal

Location

Centro Hospitalar de Lisboa Norte E.P.E Hospital Pulido Valente

Lisbon, 1769-001, Portugal

Location

Instituto Portugues de Oncologia Do Porto Francisco Gentil Epe - PPDS

Porto, 4200-072, Portugal

Location

Centro Hospitalar de Sao Joao, E.P.E.

Porto, 4200, Portugal

Location

GBUZ Saint Petersburg Clinical Research Center of Specialized Types of Care (Oncology)

Saint Petersburg, Leningradskaya Oblast', 197758, Russia

Location

LLC "EuroCityClinic"

Saint Petersburg, Sankt-Peterburg, 197022, Russia

Location

National Cancer Centre

Singapore, 169608, Singapore

Location

Chungbuk National University Hospital

Cheongju-si, North Chungcheong, 28644, South Korea

Location

Pusan National University Hospital

Busan, 602-739, South Korea

Location

National Cancer Center

Goyang, 410769, South Korea

Location

Chonnam National University Hwasun Hospital

Jeongnam, 519-763,, South Korea

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Asan Medical Center - PPDS

Seoul, 05505, South Korea

Location

Samsung Medical Center PPDS

Seoul, 06351, South Korea

Location

The Catholic University of Korea, Seoul St. Mary's Hospital

Seoul, 06591, South Korea

Location

Severance Hospital Yonsei University Health System - PPDS

Seoul, 120-752, South Korea

Location

ICO lHospitalet Hospital Duran i Reynals

L'Hospitalet de Llobregat, Barcelona, 08907, Spain

Location

Hospital Universitario A Coruna

A Coruña, 15006, Spain

Location

Hospital General Universitario de Alicante

Alicante, 03010, Spain

Location

Hospital Universitario Vall d'Hebron - PPDS

Barcelona, 08035, Spain

Location

Hospital Clinic de Barcelona

Barcelona, 08036, Spain

Location

C.H. Regional Reina Sofia - PPDS

Córdoba, 14004, Spain

Location

Hospital Universitario Fundacion Jimenez Diaz

Madrid, 28040, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Hospital Universitario La Paz - PPDS

Madrid, 28046, Spain

Location

Hospital Universitari i Politecnic La Fe de Valencia

Valencia, 46026, Spain

Location

Karolinska Universitetssjukhuset Solna

Stockholm, Södermanland County, Sweden

Location

Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation

Dalin, 622, Taiwan

Location

National Taiwan University Hospital - YunLin Branch

Douliu, 640, Taiwan

Location

Kaohsiung Medical University - Chung-Ho Memorial Hospital

Kaohsiung City, 807, Taiwan

Location

E-DA hospital

Kaohsiung City, 82445, Taiwan

Location

Taichung Veterans General Hospital

Taichung, 407, Taiwan

Location

National Cheng Kung University Hospital

Tainan, 704, Taiwan

Location

Chi Mei Medical Center, Liouying

Tainan, 736, Taiwan

Location

National Taiwan University Hospital

Taipei, 10002, Taiwan

Location

Taipei Veterans General Hospital

Taipei, 112, Taiwan

Location

Baskent University Medical Faculty Adana Practice and Research Center

Yüreğir, Adana, 01120, Turkey (Türkiye)

Location

T.C. Saglik Bakanligi Goztepe Prof. Dr. Suleyman Yalcin City Hospital

Kadıköy, Istanbul, 34772, Turkey (Türkiye)

Location

Ege University Medical Faculty

Bornova, İzmir, 35100, Turkey (Türkiye)

Location

SAKARYA University Medical Faculty

Karaman, Sakarya, 54290, Turkey (Türkiye)

Location

Hacettepe University Medical Faculty

Ankara, 06100, Turkey (Türkiye)

Location

Trakya University Medical Faculty

Edirne, 22030, Turkey (Türkiye)

Location

Municipal Non-profit Enterprise "City Clinical Hospital # 4" of Dnipro City Council - PPDS

Dnipropetrovsk, Dnipropetrovsk Oblast, 49102, Ukraine

Location

Communal Non-profit Enterprise Regional Center of Oncology

Kharkiv, Kharkivs’ka Oblast’, 61070, Ukraine

Location

Private Enterprise Private Manufacturing Company Acinus

Kropyvnytskyi, 25006, Ukraine

Location

University College London Hospitals (UCLH)

London, London, City of, NW1 2PG, United Kingdom

Location

Royal Marsden Hospital - Surrey

Sutton, Surrey, SM2 5PT, United Kingdom

Location

Clatterbridge Centre For Oncology

Bebington, Wirral, CH63 4JY, United Kingdom

Location

Leicester General Hospital

Leicester, LE1 5WW, United Kingdom

Location

The Christie NHS Foundation Trust - PPDS

Manchester, M20 4GJ, United Kingdom

Location

Related Publications (1)

• Janne PA, Wang BC, Cho BC, Zhao J, Li J, Hochmair M, Peters S, Besse B, Pavlakis N, Neal JW, Kato T, Wu YL, Nguyen D, Lin J, Lin J, Vranceanu F, Szumski A, Lin HM, Fram RJ, Mok TSK. First-Line Mobocertinib Versus Platinum-Based Chemotherapy in Patients With EGFR Exon 20 Insertion-Positive Metastatic Non-Small Cell Lung Cancer in the Phase III EXCLAIM-2 Trial. J Clin Oncol. 2025 May;43(13):1553-1563. doi: 10.1200/JCO-24-01269. Epub 2025 Jan 29.

  PMID: 39879577 DERIVED

Related Links

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MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

mobocertinib; Pemetrexed; Cisplatin; Carboplatin

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Coordination Complexes; Organic Chemicals

Study Officials

• Study Director

  Takeda

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 7, 2019
• First Posted: October 16, 2019
• Study Start: January 10, 2020
• Primary Completion (Estimated): October 31, 2026
• Study Completion (Estimated): October 31, 2026
• Last Updated: March 30, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• 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.

Locations

IL (2); AU (3); CA (4); DE (6); HK (6); GR (2); IT (9); JP (12); US (11); BE (3); SG (1); KR (9); ES (10); SE (1); TW (9); TU (6); NL (1); FR (11); RU (2); GB (5); UA (3); CN (12); PT (5)