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NCT07195695PHASE3Recruiting

Beamion LUNG-3: Adjuvant Zongertinib vs Standard Treatment in People With Completely Resected Stage II-IIIB NSCLC Harboring Activating HER2 TKD Mutations

Boehringer Ingelheim

Start Date

1/16/2026

Completion Date

9/2/2036

Summary

Beamion LUNG-3 study evaluates whether zongertinib, an oral HER2-targeted treatment, can improve outcomes compared with standard adjuvant treatment in adults with completely resected Stage II-IIIB non-small cell lung cancer (NSCLC) whose tumors have activating HER2 tyrosine kinase domain (TKD) mutations. Eligible participants must have undergone curative-intent surgery and received guideline-appropriate perioperative systemic therapy, either neoadjuvant platinum-based chemotherapy with or without immunotherapy, or adjuvant platinum-based chemotherapy. Participants are randomized 1:1 to receive zongertinib or standard of care, which may consist of approved adjuvant immunotherapy or active surveillance, based on local practice guidelines. The main purpose of the study is to determine whether zongertinib can prolong disease-free survival compared to standard treatment. Safety and patient-reported outcomes are also assessed.

Detailed Description

This is a global, randomized, open-label, Phase 3 study designed to assess the efficacy and safety of zongertinib as adjuvant therapy in participants with completely resected Stage II-IIIB NSCLC and HER2 TKD-activating mutations. Participants must have undergone complete resection and received perioperative systemic therapy consistent with current standards, including either neoadjuvant platinum-based chemotherapy with or without immunotherapy, or adjuvant platinum-based chemotherapy. After completing surgery and required systemic treatment, eligible participants are randomized 1:1 to receive either Zongertinib taken orally once daily for up to 3 years, or standard treatment, which may include an approved adjuvant immunotherapy agent administered according to its label, or observation, depending on local clinical practice and patient status. The primary objective is to evaluate whether zongertinib improves disease-free survival (DFS) compared with standard treatment. Secondary objectives include overall survival (OS), safety, tolerability, and patient-reported outcomes.

Eligibility Criteria

Age Range: 18 years to No maximum

Inclusion criteria: 1. Signed and dated written informed consent in accordance with ICH-GCP and local legislation prior to admission to the trial 2. Patients must be ≥18 years old or over the legal age of consent in their country 3. Male or female patients. Women of childbearing potential (WOCBP) must be ready and able to use dual highly effective methods of birth control per ICH M3 (R2) that result in a low failure rate of less than 1% per year when used consistently and correctly. A list of contraception methods meeting these criteria is provided in the patient information and in the study protocol 4. HER2 mutation: Documented Tyrosine kinase domain (TKD) activating Human epidermal growth factor receptor 2 (HER2) mutations 5. Histology and tumor sample: Histologically confirmed diagnosis of primary NSCLC 6. An archival tumor tissue sample must be submitted to the central laboratory after inclusion of the patient to retrospectively confirm the HER2 status 7. Staging: Pretherapeutic classification not exceeding Stage IIIB 8. Performance status and organ function: * Eastern Cooperative Oncology Group (ECOG) score of 0 or 1 * Adequate organ function based on laboratory values Further inclusion criteria apply. Exclusion criteria: 1. Diagnosis of NSCLC with mixed histology/positive neuroendocrine markers (synaptophysin/CD56) 2. Major surgery (major according to the investigator's assessment) performed within 4 weeks prior to randomization 3. Treatment with radiation therapy for primary NSCLC 4. Co-occurring actionable mutation with approved targeted therapy (e.g. Epidermal growth factor receptor (EGFR) or Anaplastic lymphoma kinase (ALK)) 5. Any investigational drug within 5 half-lives of the compound or any of its related material, if known 6. History or presence of * Active or known pre-existing or history of non-infectious interstitial lung disease/pneumonitis * Active infectious disease requiring systemic therapy * Uncontrolled gastrointestinal disorders affecting drug intake/absorption * Previous or concomitant malignancies within the last 3 years, except certain effectively treated cancers * Significant and/or uncontrolled cardiovascular abnormalities, QT interval corrected for heart rate by Fridericia formula (QTcF) \>470 msec, or ejection fraction \<50% Further exclusion criteria apply.

Interventions

DRUG

Zongertinib

DRUG

Pembrolizumab

DRUG

Atezolizumab

DRUG

Durvalumab

DRUG

Nivolumab

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Conditions

Non-small Cell Lung Cancer

Locations

ClinRé 001-022 (Premier Cancer Care and Infusion Center)

Fresno, California 93710

United States

OPN Healthcare, Inc.

Glendale, California 91203

United States

University of California Irvine

Irvine, California 92697

United States

Sutter Health

Roseville, California 95661

United States

University of California San Francisco

San Francisco, California 94143

United States

Sarcoma Oncology Center

Santa Monica, California 90403

United States

University of California Los Angeles

Santa Monica, California 90404

United States

Northern California Kaiser Permanente

Vallejo, California 94589

United States

George Washington University Cancer Center

Washington D.C., District of Columbia 20037

United States

Mid Florida Hematology and Oncology Center

Orange City, Florida 32763

United States

Piedmont Cancer Institute

Atlanta, Georgia 30318

United States

Northwest Georgia Oncology Centers

Marietta, Georgia 30060

United States

Saint Alphonsus Regional Medical Center - Boise

Boise, Idaho 83706

United States

Northwestern University

Chicago, Illinois 60611

United States

University of Illinois Hospital and Health Sciences System

Chicago, Illinois 60612

United States

Duly Health and Care - Lisle

Lisle, Illinois 60532

United States

Dana-Farber Cancer Institute

Boston, Massachusetts 02215

United States

Cancer Care Specialists

Reno, Nevada 89511

United States

Laura & Isaac Perlmutter Cancer Center at NYU Langone Health

New York, New York 10016

United States

Memorial Sloan-Kettering Cancer Center

New York, New York 10065

United States

Levine Cancer Institute

Charlotte, North Carolina 28204

United States

Durham VA Health Care System

Durham, North Carolina 27705

United States

Providence Cancer Institute

Portland, Oregon 97213

United States

Providence Cancer Institute

Portland, Oregon 97225

United States

Hendrick Health

Abilene, Texas 79601

United States

The University of Texas MD Anderson Cancer Center

Houston, Texas 77030

United States

Community Cancer Trials of Utah

Ogden, Utah 84405

United States

Virginia Cancer Specialists, PC

Fairfax, Virginia 22031

United States

Centro de Investigaciones Médicas y Desarrollo LC S.R.L. (LC Investigación)

CABA, 1185

Argentina

Hospital Britanico de Buenos Aires

CABA, 1280AEB

Argentina

Centro Oncologico Korben

CABA, 1426

Argentina

Clinica Adventista Belgrano

CABA, 1430

Argentina

Instituto Medico Especializado Alexander Fleming

Capital Federal, C1426ANZ

Argentina

Royal North Shore Hospital

Sydney, New South Wales 2065

Australia

Princess Alexandra Hospital

Woolloongabba, Queensland 4102

Australia

Flinders Medical Centre

Bedford Park, South Australia 5042

Australia

Austin Health

Heidelberg, Victoria 3084

Australia

St John of God Subiaco Hospital

Subiaco, Western Australia 6008

Australia

Medical University of Innsbruck

Innsbruck, A-6020

Austria

Clinic Floridsdorf

Vienna, 1210

Austria

Edegem - UNIV UZ Antwerpen

Edegem, 2650

Belgium

UZ Leuven

Leuven, 3000

Belgium

Centre Hospitalier Universitaire de Liège

Liège, 4000

Belgium

Hospital de Amor

Barretos, 14784-400

Brazil

NewData Clinical Research - Maceió

Maceió, 57020-360

Brazil

Centro de Pesquisa Oncology Natal

Natal, 59020-400

Brazil

Centro Gaúcho Integrado de Oncologia, Hematologia, Ensino e Pesquisa

Porto Alegre, 90110-270

Brazil

CEPHO - Centro de Estudos e Pesquisas em Hematologia e Oncologia

Santo André, 09060-650

Brazil

ICESP - Instituto do Cancer do Estado de Sao Paulo

São Paulo, 01246-000

Brazil

A.C. Camargo

São Paulo, 01509-010

Brazil

Cross Cancer Institute (University of Alberta)

Edmonton, Alberta T6G 1Z2

Canada

Princess Margaret Cancer Centre

Toronto, Ontario M5G 2M9

Canada

Centro de Estudios Clinicos SAGA

Providencia, 7500653

Chile

Bradford Hill- Centro de Investigación Clínica

Recoleta, 8420383

Chile

China-Japan Friendship Hospital

Beijing, 100029

China

Beijing Chest Hospital, Capital Medical University

Beijing, 101149

China

The First Hospital of Jilin University

Changchun, 130000

China

Xiangya Hospital, Central South University

Changsha, 410008

China

Hunan Province Tumor Hospital

Changsha, 410013

China

Sichuan Cancer Hospital

Chengdu, 610041

China

West China Hospital, Sichuan University

Chengdu, 610041

China

The First Affiliated Hospital,Sun Yat-sen University

Guangzhou, 510080

China

The First Affiliated Hospital, Zhejiang University

Hangzhou, 310003

China

Zhejiang Cancer Hospital

Hangzhou, 310022

China

Harbin Medical University Cancer Hospital

Harbin, 150081

China

Shandong Cancer Hospital

Jinan, 250117

China

Yunnan Provincial Tumor Hospital

Kunming, 650118

China

Linyi Cancer Hospital

Linyi, 276034

China

The First Affiliated Hospital of Nanchang University

Nanchang, 330006

China

Nanjing Drum Tower Hospital

Nanjing, 210008

China

Ningbo Second Hospital

Ningbo, 315010

China

Shanghai East Hospital

Shanghai, 200121

China

Shanghai Pulmonary Hospital

Shanghai, 200433

China

Hebei Provincial Tumor Hospital

Shijiazhuang, 50035

China

The First Affiliated Hospital of Soochow University

Suzhou, 215006

China

Taizhou Hospital of Zhejiang Province

Taizhou, 317099

China

Tianjin Cancer Hospital

Tianjin, 300060

China

Tianjin Medical University General Hospital

Tianjin, 30052

China

Wuhan Union Hospital

Wuhan, 430056

China

Affiliated Hospital, Xuzhou Medical college

Xuzhou, 221009

China

Northern Jiangsu People's Hospital

Yangzhou, 225001

China

Henan Cancer Hospital

Zhengzhou, 450008

China

Sjællands Universitetshospital

Roskilde, 4000

Denmark

Hôpital Louis Pradel

Bron, 69677

France

HOP Nord

Marseille, 13915

France

HOP Nord Laennec

Nantes, 44093

France

HOP Tenon - One AP-HP

Paris, 75970

France

HOP Pontchaillou

Rennes, 35033

France

Centre Régional de Lutte Contre le Cancer Paul Stauss

Strasbourg, 67200

France

Hôpital Larrey - CHU de Toulouse

Toulouse, 31059

France

Institut Gustave Roussy

Villejuif, 94805

France

Charité - Universitätsmedizin Berlin

Berlin, 12203

Germany

Universitätsklinikum Köln (AöR)

Cologne, 50937

Germany

Klinikum Esslingen

Esslingen am Neckar, 73730

Germany

Varisano LungenZentrum (VLZ)

Frankfurt, 65929

Germany

Asklepios Fachkliniken München-Gauting

Gauting, 82131

Germany

LungenClinic Grosshansdorf GmbH

Großhansdorf, 22927

Germany

Thoraxklinik-Heidelberg gGmbH am Universitätsklinikum Heidelberg

Heidelberg, 69126

Germany

Pius-Hospital, Oldenburg

Oldenburg, 26121

Germany

Universitätsklinikum Würzburg AÖR

Würzburg, 97078

Germany

Henry Dunant Hospital, Athens

Athens, 11526

Greece

Chest Hospital of Athens "Sotiria"

Athens, 11527

Greece

University General Hospital Attikon

Athens, 12462

Greece

Queen Elizabeth Hospital-Hong Kong-51727

Hong Kong, 51727

Hong Kong

Prince of Wales Hospital-Hong Kong-20715

Hong Kong, 999077

Hong Kong

Princess Margaret Hospital

Hong Kong, 999077

Hong Kong

Queen Mary Hospital

Hong Kong,

Hong Kong

Rambam Health Care Campus

Haifa, 3109601

Israel

Shaare Zedek Medical Center, Jerusalem 91031

Jerusalem, 9103102

Israel

Meir Medical Center

Kfar Saba, 44281

Israel

Sheba Medical Center

Ramat Gan, 5262000

Israel

Sourasky Medical Center

Tel Aviv, 6093246

Israel

Istituto Tumori Giovanni Paolo II

Bari, 70124

Italy

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, 20133

Italy

Humanitas Istituto Clinico Catanese S.p.A.

Misterbianco (CT), 95045

Italy

Istituto Nazionale IRCCS Tumori Fondazione Pascale

Naples, 80131

Italy

AOU San Luigi Gonzaga

Orbassano (TO), 10043

Italy

Istituti Fisioterapici Ospitalieri

Roma, 144

Italy

Istituto Clinico Humanitas

Rozzano (MI), 20089

Italy

Azienda Ospedaliera Universitaria Integrata Verona

Verona, 37126

Italy

Aichi Cancer Center Hospital

Aichi, Nagoya, 464-8681

Japan

Fujita Health University Hospital

Aichi, Toyoake, 470-1192

Japan

National Cancer Center Hospital East

Chiba, Kashiwa, 277-8577

Japan

Kyushu University Hospital

Fukuoka, Fukuoka, 812-8582

Japan

Hospital of the University of Occupational and Environmental Health

Fukuoka, Kitakyushu, 807-8556

Japan

Hiroshima University Hospital

Hiroshima, Hiroshima, 734-8551

Japan

Hokkaido Cancer Center

Hokkaido, Sapporo, 003-0804

Japan

Kitasato University Hospital

Kanagawa, Sagamihara, 252-0375

Japan

Kanagawa Cancer Center

Kanagawa, Yokohama, 241-8515

Japan

Sendai Kousei Hospital

Miyagi, Sendai, 981-0914

Japan

Niigata Cancer Center Hospital

Niigata, Niigata, 951-8566

Japan

Okayama University Hospital

Okayama, Okayama, 700-8558

Japan

Kansai Medical University Hospital

Osaka, Hirakata, 573-1191

Japan

Osaka International Cancer Institute

Osaka, Osaka, 541-8567

Japan

Kindai University Hospital

Osaka, Sakai, 590-0197

Japan

National Hospital Organization Kinki-Chuo Chest Medical Center

Osaka, Sakai, 591-8555

Japan

Saitama Medical University International Medical Center

Saitama, Hidaka, 350-1298

Japan

Saitama Cancer Center

Saitama, Kitaadachi-gun, 362-0806

Japan

Shizuoka Cancer Center

Shizuoka, Sunto-gun, 411-8777

Japan

Jichi Medical University Hospital

Tochigi, Shimotsuke, 329-0498

Japan

Juntendo University Hospital

Tokyo, Bunkyo-ku, 113-8431

Japan

National Cancer Center Hospital

Tokyo, Chuo-ku, 104-0045

Japan

Japanese Foundation for Cancer Research

Tokyo, Koto-ku, 135-8550

Japan

Tokyo Medical University Hospital

Tokyo, Shinjuku-ku, 160-0023

Japan

Wakayama Medical University Hospital

Wakayama, Wakayama, 641-8510

Japan

Centro Oncologico Internacional

Jalisco, 45640

Mexico

Centro de Infusion Profesional Integral (CIPI)

Mexico City, 14210

Mexico

Instituto Nacional de Cancerologia

México, 14080

Mexico

Centro Oncologico Personalizado

México, 6760

Mexico

Centro Medico Zambrano Hellion

Monterrey, 66278

Mexico

Nederlands Kanker Instituut - Antoni van Leeuwenhoek Amsterdam (METC AVL)

Amsterdam, 1066CX

Netherlands

Hospital CUF Tejo

Lisbon, 1350-352

Portugal

Hospital da Luz

Lisbon, 1500-650

Portugal

Hospital CUF Porto

Porto, 4100-180

Portugal

IPO Porto Francisco Gentil, EPE

Porto, 4200-072

Portugal

Lotus Med

Bucharest, 12292

Romania

Memorial Healthcare International

Bucharest, 13823

Romania

Ovidius Clinical Hospital S.R.L

Ovidiu, 905900

Romania

Polaris Medical S.A.

Suceagu/ Cluj Napoca, 407062

Romania

National Cancer Centre Singapore

Singapore, 168583

Singapore

National Cancer Center

Goyang, 10408

South Korea

Seoul National University Bundang Hospital

Seongnam, 13620

South Korea

Seoul National University Hospital

Seoul, 3080

South Korea

Severance Hospital

Seoul, 3722

South Korea

Asan Medical Center

Seoul, 5505

South Korea

Samsung Medical Center

Seoul, 6351

South Korea

The Catholic University of Korea, St.Vincent's Hospital

Suwon, 16247

South Korea

Ajou University Hospital

Suwon, 16499

South Korea

Hospital del Mar

Barcelona, 8003

Spain

Hospital Universitari Vall D Hebron

Barcelona, 8035

Spain

Hospital Universitario De Burgos

Burgos, 9006

Spain

Hospital General Universitario de Elche

Elche, 3203

Spain

Hospital Jerez de la Frontera

Jerez de la Frontera, 11407

Spain

Hospital Duran i Reynals

L'Hospitalet de Llobregat, 8908

Spain

Hospital Universitario Ramon Y Cajal

Madrid, 28034

Spain

Fundación Jiménez Díaz

Madrid, 28040

Spain

Hospital Universitario 12 de Octubre

Madrid, 28041

Spain

Hospital Puerta de Hierro

Majadahonda, 28222

Spain

Hospital Universitario Virgen de la Victoria

Málaga, 29010

Spain

Complejo Hospitalario de Navarra

Pamplona, 31008

Spain

Salut Sant Joan de Reus

Reus, 43204

Spain

Hospital Virgen del Rocío

Seville, 41013

Spain

Hospital Clinico Universitario de Valencia

Valencia, 46010

Spain

Sahlgrenska Universitetsjukhuset

Gothenburg, 413 46

Sweden

Karolinska Universitetssjukhuset Solna

Stockholm, 171 76

Sweden

Kaohsiung Medical University Chung-Ho Memorial Hospital

Kaohsiung City, 807

Taiwan

China Medical University Hospital

Taichung, 40447

Taiwan

National Taiwan University Hospital

Taipei, 10048

Taiwan

Taipei Veterans General Hospital

Taipei, 11217

Taiwan

Tri-Service General Hospital

Taipei, 114

Taiwan

Chang Gung Memorial Hospital, Linkou

Taoyuan City, 333

Taiwan

Sağlık Bilimleri Üniversitesi Gülhane Eğitim ve Araştırma Hastanesi

Ankara, 6018

Turkey (Türkiye)

Medeniyet University

Istanbul, 34862

Turkey (Türkiye)

Velindre Cancer Centre

Cardiff, CF14 2TL

United Kingdom

Western General Hospital

Edinburgh, EH4 2XU

United Kingdom

Guy's Hospital

London, SE1 9RT

United Kingdom

The Royal Marsden Hospital, Chelsea

London, SW3 6JJ

United Kingdom

The Christie

Manchester, M20 4BX

United Kingdom

The Royal Marsden Hospital, Sutton

Sutton, SM2 5PT

United Kingdom