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

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

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04129502
• Other study ID #: TAK-788-3001
• Secondary ID: NL201912122019-0
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: January 10, 2020
• Est. completion date: December 30, 2024

Study information

• Verified date: May 2024
• Source: Takeda
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 354
• Est. completion date: December 30, 2024
• Est. primary completion date: December 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Advanced/Metastatic Non-Small Cell Lung Cancer (NSCLC)
• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms

Intervention

Drug:
• TAK-788
TAK-788 capsule
• Pemetrexed
Pemetrexed IV infusion
• Cisplatin
Cisplatin IV infusion
• Carboplatin
Carboplatin IV infusion

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Takeda

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Belgium,  Canada,  China,  France,  Germany,  Greece,  Hong Kong,  Israel,  Italy,  Japan,  Korea, Republic of,  Netherlands,  Portugal,  Russian Federation,  Singapore,  Spain,  Sweden,  Taiwan,  Turkey,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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