RecruitingPhase 3NCT07128199

A Study to Assess the Efficacy and Safety of Zipalertinib Versus Placebo for Adjuvant Treatment in Participants With Stage IB-IIIA NSCLC With Uncommon EGFR Mutations, Following Complete Tumor Resection

A Randomized, Placebo-Controlled, Double-Blind, Multi-Center Phase 3 Study of Zipalertinib Plus Adjuvant Chemotherapy Versus Placebo Plus Adjuvant Chemotherapy in Stage IB-IIIA NSCLC Patients With Uncommon EGFR Mutations Following Complete Tumor Resection (REZILIENT4)

Sponsor

Taiho Oncology, Inc.

Enrollment

360 participants

Start Date

Dec 22, 2025

Study Type

INTERVENTIONAL

Conditions

Lung Cancer EGFR NSCLC, Stage IB-IIIA Adjuvant Post-surgical Exon 20 Early Stage Lung Cancer Uncommon EGFR Mutations

Summary

The purpose of this study is to compare the efficacy of zipalertinib combined with adjuvant chemotherapy versus placebo combined with adjuvant chemotherapy in participants with early stage (stage IB-IIIA) resected non-small cell lung cancer (NSCLC) harboring uncommon epidermal growth factor receptor mutation (EGFRmt).

Eligibility

Min Age: 18 Years

Plain Language Summary

Simplified for easier understanding

This study is comparing a targeted therapy drug called zipalertinib against a placebo in people with early-stage non-small cell lung cancer (NSCLC) that has been completely removed by surgery and carries a specific type of EGFR gene mutation. **You may be eligible if...** - You have been diagnosed with NSCLC with an uncommon EGFR mutation (such as exon 20 insertion, G719X, L861Q, or S768I) - Your cancer was completely removed by surgery (stages IB to IIIA) - You have had brain imaging before or after surgery - You have not received any prior systemic therapy or radiation for this cancer **You may NOT be eligible if...** - You have previously taken zipalertinib or any other EGFR-targeting drug - You received chemotherapy or radiation before or after surgery for this cancer - You are currently in another clinical trial - Your cancer has common EGFR mutations (like exon 19 deletion or L858R) Talk to your doctor to see if this trial is right for you.

This summary was AI-generated to explain the trial in plain language. It is not medical advice. Always discuss eligibility with your doctor before enrolling in a clinical trial.

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Interventions

DRUGCisplatin

IV infusion.

DRUGCarboplatin

IV infusion.

DRUGPemetrexed

IV infusion.

DRUGTAS6417

Oral tablets.

DRUGZipalertinib Matching-placebo

Oral tablets.

Locations(253)

Alaska Oncology and Hematology

Anchorage, Alaska, United States

City of Hope Comprehensive Cancer Center - Duarte

Duarte, California, United States

City of Hope Comprehensive Cancer Center Orange County Lennar Foundation Cancer Center

Irvine, California, United States

Scripps Clinic Torrey Pines

La Jolla, California, United States

Kaiser Permanente - Vallejo Medical Center

Vallejo, California, United States

Georgetown University School of Medicine

Washington D.C., District of Columbia, United States

D&H Cancer Research Center - Margate

Margate, Florida, United States

Alpha Oncology Research

Orange City, Florida, United States

City of Hope - Atlanta

Newnan, Georgia, United States

University of Illinois Medical Center

Chicago, Illinois, United States

Profound Research LLC at Michigan Hematology and Oncology Consultants

Dearborn, Michigan, United States

Henry Ford Health System

Detroit, Michigan, United States

Memorial Sloan Kettering Cancer Center - Basking Ridge

Basking Ridge, New Jersey, United States

Memorial Sloan Kettering Cancer Center - Monmouth

Middletown, New Jersey, United States

Memorial Sloan Kettering Cancer Center - Bergen

Montvale, New Jersey, United States

Memorial Sloan Kettering Cancer Center - Commack

Commack, New York, United States

Memorial Sloan Kettering Cancer Center - Westchester

Harrison, New York, United States

Long Island Jewish Medical Center

Lake Success, New York, United States

Perlmutter Cancer Center - 34th Street

New York, New York, United States

Memorial Sloan Kettering Cancer Center - New York

New York, New York, United States

Memorial Sloan Kettering Cancer Center - Nassau

Uniondale, New York, United States

Atrium Health Wake Forest Baptist - Comprehensive Cancer Center

Charlotte, North Carolina, United States

Durham Veterans Affairs Health Care System

Durham, North Carolina, United States

Gabrail Cancer and Research Center

Canton, Ohio, United States

Gibbs Cancer Center and Research Institute Spartanburg

Spartanburg, South Carolina, United States

Virginia Cancer Specialists - Arlington Office

Arlington, Virginia, United States

Virginia Cancer Specialists - Fairfax Office

Fairfax, Virginia, United States

Virginia Cancer Specialists - Bristow Office

Manassas, Virginia, United States

Virginia Cancer Specialists - Reston

Reston, Virginia, United States

Virginia Cancer Specialists - Woodbridge Office

Woodbridge, Virginia, United States

Instituto Argentino de Diagnóstico y Tratamiento

Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina

Centro de Investigación Pergamino SA

Pergamino, Buenos Aires, Argentina

Hospital Universitario Austral

Pilar, Buenos Aires, Argentina

CEMAIC - Centro de Especialidades Médicas Ambulatorias e Investigación Clínica

Córdoba, Argentina

Bankstown-Lidcombe Hospital

Bankstown, New South Wales, Australia

GenesisCare - North Shore

St Leonards, New South Wales, Australia

Saint John of God - Subiaco Hospital

Subiaco, Western Australia, Australia

Universitair Ziekenhuis Antwerpen

Edegem, Antwerpen, Belgium

Algemeen Ziekenhuis Sint-Maarten

Mechelen, Antwerpen, Belgium

Universitair Ziekenhuis (UZ) Leuven - Campus Gasthuisberg

Leuven, Flemish Brabant, Belgium

NOHC - Núcleo de Oncologia e Hematologia do Ceará - José Lourenço

Fortaleza, Ceará, Brazil

Centro Regional Integrado de Oncologia

Fortaleza, Ceará, Brazil

Centro de Pesquisas Clínicas Em Oncologia - CPCO

Cachoeiro de Itapemirim, Espírito Santo, Brazil

Hospital Santa Rita

Vitória, Espírito Santo, Brazil

Núcleo de Oncologia da Bahia Ondina - NOB

Salvador, Estado de Bahia, Brazil

Oncoclinicas Oncovida - Brasilia

Brasília, Federal District, Brazil

Cetus Oncologia - Unidade Belo Horizonte

Belo Horizonte, Minas Gerais, Brazil

Cenantron Centro Avançado de Tratamento Oncológico

Belo Horizonte, Minas Gerais, Brazil

Centro Integrado de Oncologia de Curitiba (CIONC)

Curitiba, Paraná, Brazil

Instituto de Medicina Integral Professor Fernando Figueira

Recife, Pernambuco, Brazil

Centro de Pesquisa Vencer e Oncoclínica - Teresina

Teresina, Piauí, Brazil

Instituto D'Or de Pesquisa e Ensino - Rio de Janeiro

Botafogo, Rio de Janeiro, Brazil

Liga Contra o Câncer - Centro Avançado de Oncologia

Natal, Rio Grande do Norte, Brazil

Clínica Viver

Centro Santa Maria, Rio Grande do Sul, Brazil

Hospital Bruno Born

Lajeado, Rio Grande do Sul, Brazil

Hospital São Vicente de Paulo

Passo Fundo, Rio Grande do Sul, Brazil

Irmandade da Santa Casa de Misericórdia Hospital - Porto Alegre

Porto Alegre, Rio Grande do Sul, Brazil

Irmandade da Santa Casa de Misericórdia Hospital - Porto Alegre

Porto Alegre, Rio Grande do Sul, Brazil

Hospital Mãe de Deus - Centro Integrado de Oncologia

Porto Alegre, Rio Grande do Sul, Brazil

Grupo ELORA

Florianópolis, Santa Catarina, Brazil

CHO Centro - Centro de Hematologia e Oncologia de Joinville

Joinville, Santa Catarina, Brazil

Fundação Pio XII - Hospital de Câncer de Barretos - Hospital de Amor

Barretos, São Paulo, Brazil

Hospital Amaral Carvalho

Jaú, São Paulo, Brazil

Instituto de Oncologia de Sorocaba

Sorocaba, São Paulo, Brazil

A Beneficência Portuguesa de São Paulo

São Paulo, Brazil

Instituto de Assistência Médica ao Servidor Público Estadual

São Paulo, Brazil

Cross Cancer Institute

Edmonton, Alberta, Canada

William Osler Health System - Brampton Civic Hospital

Brampton, Ontario, Canada

London Health Sciences Centre

London, Ontario, Canada

Sunnybrook Health Sciences Centre - Bayview Campus

Toronto, Ontario, Canada

Princess Margaret Cancer Centre

Toronto, Ontario, Canada

Hôpital Saint-André

Bordeaux, Aquitane, France

Hôpital Louis Pradel

Bron, Auvergne-Rhône-Alpes, France

Hôpital de la Croix Rousse

Lyon, Auvergne-Rhône-Alpes, France

Centre Léon Bérard

Lyon, Auvergne-Rhône-Alpes, France

Centre Hospitalier Lyon-Sud

Pierre-Bénite, Auvergne-Rhône-Alpes, France

L'Hôpital Nord-Ouest (HNO) - Villefranche-sur-Saône

Villefranche-de-Rouergue, Aveyron, France

Hôpital Côte De Nacre

Caen, Basse-Normandie, France

Centre Hospitalier Universitaire de Nîmes

Nîmes, Gard, France

Hôpital Emile Muller

Mulhouse, Grand Est, France

Hôpital Pontchaillou

Rennes, Ille-et-Vilaine, France

Centre Hospitalier Universitaire De Nantes - Hôpital Nord Laennec

Saint-Herblain, Loire-Atlantique, France

Centre Hospitalier Universitaire d'Angers

Angers, Maine-et-Loire, France

CHU d Angers

Angers, Maine-et-Loire, France

Institut de Cancérologie de l'Ouest - Angers

Angers, Maine-et-Loire, France

CHU de Nimes - Caremeau Nord

Nîmes, Occitanie, France

Centre Hospitalier Le Mans

Le Mans, Pays de la Loire Region, France

Hopital Prive du Confluet

Nantes, Pays de la Loire Region, France

Hôpital Privé du Confluent

Nantes, Pays de la Loire Region, France

Hopital Nord Ouest

Gleizé, Rhône, France

Gustave Roussy

Villejuif, Val-De-Marne, France

Hôpital Universitaire Pitié Salpêtrière

Paris, France

Hôpital Ambroise-Paré

Boulogne-Billancourt, Île-de-France Region, France

Centre Hospitalier Intercommunal de Créteil

Créteil, Île-de-France Region, France

Groupe Hospitalier Paris Saint-Joseph

Paris, Île-de-France Region, France

Hôpital Bichat - Claude-Bernard

Paris, Île-de-France Region, France

SLK-Kliniken - Fachklinik Löwenstein

Löwenstein, Baden-Wurttemberg, Germany

Krankenhaus Nordwest

Frankfurt am Main, Hesse, Germany

Universitätsklinikum Gießen und Marburg - Gießen

Giessen, Hesse, Germany

Kliniken der Stadt Köln

Cologne, North Rhine-Westphalia, Germany

Saint Savvas Anticancer - Oncological Hospital of Athens

Athens, Attica, Greece

General Hospital for Thoracic Diseases Sotiria

Athens, Attica, Greece

Metaxa Cancer Hospital of Piraeus

Athens, Attica, Greece

BioClinic Thessaloniki

Athens, Central Macedonia, Greece

Interbalkan Medical Center of Thessaloniki

Thessaloniki, Central Macedonia, Greece

Hong Kong Sanatorium and Hospital

Happy Valley, Hong Kong

Humanity & Health Clinical Trial Centre

Hong Kong, Hong Kong

Queen Mary Hospital - Hong Kong

Hong Kong, Hong Kong

Princess Margaret Hospital

Kowloon, Hong Kong

Istituto Romagnolo per lo Studio dei Tumori "Dino Amadori" - IRST

Meldola, Forlì-Cesena, Italy

Azienda Socio Sanitaria Territoriale (ASST) di Bergamo Ovest

Legnano, Milan, Italy

Fondazione IRCCS - Istituto Nazionale dei Tumori

Milan, Milan, Italy

Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda

Milan, Milan, Italy

Istituto Europeo di Oncologia

Milan, Milan, Italy

Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda

Milan, Milan, Italy

Ospedale del Mare

Naples, Naples, Italy

Ospedale Santa Maria delle Croci di Ravenna

Lugo, Ravenna, Italy

Azienda Ospedaliera Complesso Ospedaliero San Giovanni - Addolorata

Roma, Rome, Italy

Istituto di Candiolo - Fondazione del Piemonte per l'Oncologia

Candiolo, Torino, Italy

Azienda Ospedaliero - Universitaria San Luigi Gonzaga

Orbassano, Torino, Italy

Ospedale P. Pederzoli - Casa di Cura Privata S.p.A.

Peschiera del Garda, Verona, Italy

Azienda Ospedaliera Nazionale SS. Antonio e Biagio e Cesare Arrigo - Alessandria

Alessandria, Italy

Azienda Ospedaliero Universitaria Delle Marche

Ancona, Italy

Humanitas Gavazzeni

Bergamo, Italy

Azienda Socio Sanitaria Territoriale (ASST) Papa Giovanni XXIII

Bergamo, Italy

Azienda Ospedaliero-Universitaria di Bologna - Policlinico Sant Orsola-Malpighi

Bologna, Italy

Azienda Ospedaliero Universitaria Policlinico Gaspare Rodolico - San Marco - Catania/ Presidio G. Rodolico

Catania, Italy

Azienda Unita Sanitaria Locale toscana Nord Ovest

Livorno, Italy

Azienda Unità Sanitaria Locale Toscana Nord Ovest

Livorno, Italy

Azienda Ospedaliera Complesso Ospedaliero San Giovanni - Addolorata

Milan, Italy

Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) - Ospedale San Raffaele

Milan, Italy

Azienda Ospedaliero - Universitaria di Modena

Modena, Italy

Fondazione IRCCS Policlinico San Matteo

Pavia, Italy

Azienda Ospedaliera Universitaria Senese - L'ospedale Santa Maria alle Scotte

Siena, Italy

Azienda Ospedaliera Universitaria Integrata Verona

Verona, Italy

Nagoya Univeristy Hospital

Nagoya, Aichi-ken, Japan

Aichi Cancer Center

Nagoya, Aiti [Aichi], Japan

Kurume University Hospital

Kurume-Shi, Fukuoka, Japan

Hiroshima University Hospital

Hiroshima, Hirosima [Hiroshima], Japan

Hokkaido Cancer Center

Sapporo, Hokkaido, Japan

National Hospital Organization Kyushu Cancer Center

Fukuoka, Hukuoka [Fukuoka], Japan

Hyogo Cancer Center

Akashi, Hyōgo, Japan

Kobe University Hospital

Kobe, Hyōgo, Japan

Kanagawa Cancer Center

Yokohama, Kanagawa, Japan

Tohoku University Hospital

Sendai, Miyagi, Japan

Nagasaki University Hospital

Nagasaki, Nagasaki, Japan

Kansai Medical University Hospital

Hirakata, Osaka, Japan

Kindai University Hospital

Osakasayama-Shi, Osaka, Japan

Saitama Medical University - International Medical Center

Hidaka-Shi, Saltama, Japan

Shizuoka Cancer Center

Sunto-gun, Sizuoka [Shizuoka], Japan

National Cancer Center Hospital East

Kashiwa-shi, Tiba [Chiba], Japan

Cancer Institute Hospital of JFCR

Koto, Tokyo, Japan

Tokyo Medical University Hospital

Shinjuku-ku, Tokyo, Japan

Yamagata University Hospital

Yamagata, Yamagata, Japan

Okayama University Hospital

Okayama, Japan

Osaka City General Hospital

Osaka, Japan

Osaka Prefectural Hospital Organization - Osaka International Cancer Institute

Osaka, Japan

National Cancer Center Hospital

Tokyo, Japan

Hospital Raja Perempuan Zainab II

Kota Bharu, Kelantan, Malaysia

Hospital Pulau Pinang

Pulau Pinang, Pulau Pinang, Malaysia

Hospital Picaso

Petaling Jaya, Selangor, Malaysia

Hospital Kuala Lumpur

Kuala Lumpur, Malaysia

Sunway Medical Centre

Selangor Darul Ehsan, Malaysia

Preparaciones Oncológicas S.C.

León, Guanajuato, Mexico

Centro Oncológico Alianza XXI

Mexico City, Mexico City, Mexico

Clínica Integral Internacional de Oncología S de RL de CV

Mirador, Puebla, Mexico

Ziekenhuis St Jansdal Harderwijk

Harderwijk, Gelderland, Netherlands

Radboud Universitair Medisch Centrum

Nijmegen, Gelderland, Netherlands

Leids Universitair Medisch Centrum (LUMC)

Leiden, South Holland, Netherlands

Hospital Nacional Arzobispo Loayza

Lima Cercado, Lima region, Peru

Clínicas Oncosalud Sede Guardia Civil

San Borja, Lima region, Peru

Luis Alberto Vera Valdivia

San Borja, Lima region, Peru

IPOR - Instituto Peruano de Oncología & Radioterapia - Sede Principal

San Isidro, Lima region, Peru

Detecta Clínica

Surquillo, Lima region, Peru

4 Wojskowy Szpital Kliniczny z Polikliniką SP ZOZ

Wroclaw, Lower Silesian Voivodeship, Poland

Mruk-Med I Sp. z o.o.

Rzeszów, Podkarpackie Voivodeship, Poland

Warmińsko-mazurskie Centrum Chorób Płuc w Olsztynie

Olsztyn, Warmian-Masurian Voivodeship, Poland

Institutul Oncologic Bucuresti - Prof. Dr. Alexandru Trestioreanu

Bucharest, Bucharest, Romania

Monza Oncology Day Hospital

Bucharest, Bucharest, Romania

Centrul de Radioterapie Amethyst Cluj

Floreşti, Cluj, Romania

Ovidius Clinical Hospital

Ovidiu, Constanța County, Romania

Clinica MC Gral Ploiesti

Ploieşti, Prahova, Romania

Oncocenter - Oncologie Clinica

Timișoara, Timiș County, Romania

Spitalul Județean de Urgență Satu Mare

Satu Mare, Romania

Curie Oncology - Farrer - 10-05

Singapore, Central Singapore, Singapore

P.H Feng Research Centre

Singapore, Central Singapore, Singapore

Tan Tock Seng Hospital

Singapore, North East, Singapore

National Cancer Centre Singapore

Singapore, Singapore

Kyungpook National University Chilgok Hospital

Daegu, Daegu Gwang'yeogsi [Taegu-Kwangyokshi], South Korea

Seoul National University Bundang Hospital

Seongnam-si, Gyeonggi-do, South Korea

Catholic University of Korea St. Vincent's Hospital

Suwon, Gyeonggi-do, South Korea

Ajou University Hospital

Suwon, Gyeonggi-do, South Korea

Chungbuk National University Hospital

Cheongju-si, Gyeonggido [Kyonggi-do], South Korea

National Cancer Center - Korea

Goyang-si, Gyeonggido [Kyonggi-do], South Korea

Keimyung University Dongsan Hospital

Daegu, Gyeongsangbugdo [Kyongsangbuk-do], South Korea

Kosin University Gospel Hospital

Pusan, Gyeongsangnam-do, South Korea

Pusan National University Yangsan Hospital

Yangsan, Gyeongsangnam-do, South Korea

Gyeongsang National University Hospital

Jinju, Gyeongsangnamdo [Kyongsangnam-do], South Korea

Inha University Hospital

Incheon, Incheon Gwang'yeogsi [Inch'on-Kwangyokshi], South Korea

Chonnam National University Hwasun Hospital

Hwasun-gun, Jeollanam-do, South Korea

Jeonbuk National University Hospital

Jeonju, Jeonrabugdo [Chollabuk-do], South Korea

Korea University Anam Hospital