Clinical trial NCT06151574: Beamion LUNG-2: A Study to Test Whether Zongertinib (BI 1810631) Helps People With Advanced Non-small Cell Lung Cancer With HER2 Mutations Compared With Standard Treatment
Official title: Beamion LUNG 2: A Phase III, Open-label, Randomized, Active-controlled, Multi-centre Trial Evaluating Orally Administered Zongertinib (BI 1810631) Compared With Standard of Care as First-line Treatment in Patients With Unresectable, Locally Advanced or Metastatic Non-squamous Non-small Cell Lung Cancer Harbouring HER2 Tyrosine Kinase Domain Mutations
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Lung Cancer, Non-squamous, Non-small Cell
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2023-11-30
Enrollment: 416
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study is open to adults 18 years and older with advanced or metastatic non-small cell lung cancer. People can join the study if they have tumours with HER2 mutations and have not yet received any systemic therapy including chemotherapy for advanced or metastatic lung cancer. The purpose of this study is to find out whether a medicine called zongertinib (BI 1810631) can slow down the worsening of advanced non-small cell lung cancer better than the standard treatment available. Zongertinib may slow cancer cell growth by inhibiting HER2. This would prolong cancer re-occurrence and increase survival. Current standard treatment is pembrolizumab plus platinum-pemetrexed chemotherapy.

Participants are put into 2 groups by chance. One group receives zongertinib at regular times throughout the study and the other group receives infusions of pembrolizumab, pemetrexed and cisplatin or carboplatin (pembrolizumab plus platinum-pemetrexed chemotherapy) into a vein.

Participants may be in the study up to a maximum of 70 months. During this time, they visit the study site about every 3 weeks for study procedures. The doctors regularly check the size of the tumour with a CT or MRI scan, at the beginning of the study and every 6 weeks. After 18 months they check the tumour size every 12 weeks. Doctors regularly check whether the cancer has spread to other parts of the body. The doctors also regularly check participants' health and take note of any unwanted effects. The time it takes for the cancer to worsen is compared between the 2 groups to see whether the treatment works. The participants also fill in questionnaires about their symptoms and quality of life.


Eligibility criteria: Inclusion criteria:

1. Signed and dated written informed consent form (ICF) in accordance with International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use - Good Clinical Practice (ICH-GCP) and local legislation prior to admission to the trial.
2. Patients ≥18 years of age or over the legal age of consent in countries where that is greater than 18 years at the time of signature of the ICF.
3. Histologically or cytologically confirmed diagnosis of an advanced and/or metastatic non-squamous Non-small cell lung cancer (NSCLC).
4. Documented Human epidermal growth factor receptor 2 (HER2) mutation in the Tyrosine kinase domain (TKD) as per local lab results.
5. An archival tumor tissue sample must be submitted to the central laboratory after inclusion of the patient to retrospectively confirm the HER2 status. If no archival tissue is available, this may be acceptable in exceptional cases after written agreement with the sponsor.
6. Patients who have not received any systemic treatment for unresectable, locally advanced or metastatic disease and are not eligible for curative therapy.
7. Presence of at least one measurable lesion according to Response evaluation criteria in solid tumors (RECIST) 1.1, as determined by the local site investigator/radiology assessment.
8. Eligible to receive treatment with the selected platinum-based doublet-chemotherapy (i.e. cisplatin/pemetrexed or carboplatin/pemetrexed) and pembrolizumab in accordance with the Summaries of Product Characteristics (SmPC)/Product Information.

Further inclusion criteria apply.

Exclusion criteria:

1. Previous or concomitant malignancies other than the one treated in this trial within the last 5 years, except;

   * effectively treated non-melanoma skin cancers
   * effectively treated carcinoma in situ of the cervix
   * effectively treated ductal carcinoma in situ
   * other effectively treated malignancy that is considered cured by local treatment
2. Tumors with targetable alterations with approved available therapy.
3. Lung-specific intercurrent clinically significant severe illness based on investigators assessment.
4. Patients who must or wish to continue the intake of restricted medications or any drug considered likely to interfere with the safe conduct of the trial.
5. Major surgery (major according to the investigator's assessment) performed within 4 weeks prior to randomization or planned within 6 months after screening, e.g. hip replacement.
6. Any history of or concomitant condition that, in the opinion of the investigator, would compromise the patient's ability to comply with the trial or interfere with the evaluation of the safety and efficacy of the test drug.
7. History or presence of cardiovascular abnormalities such as uncontrolled hypertension, congestive heart failure New York Heart Association (NYHA) classification of ≥ III or IV, unstable angina or poorly controlled arrhythmia which are considered as clinically relevant by the investigator. Myocardial infarction, stroke, or pulmonary embolism within 6 months prior to randomization.
8. Any clinically important abnormalities (as assessed by the investigator) in rhythm, conduction, or morphology of resting electrocardiograms, e.g. complete left bundle branch block, third degree heart block.

Further exclusion criteria apply.

Primary outcomes:
measure: Progression-free survival (PFS) according to Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 determined by blinded central independent review
timeFrame: up to 4 years and 5 months
Secondary outcomes:
measure: Key secondary endpoint: Overall Response (OR) according to RECIST 1.1 determined by blinded central independent review
timeFrame: up to 53 months
measure: Key secondary endpoint: Change from baseline to Week 25 of Non-small cell lung cancer Symptom Assessment Questionnaire (NSCLC-SAQ) total score
timeFrame: at baseline, at week 25
measure: Key secondary endpoint: Overall Survival (OS)
timeFrame: up to 53 months
measure: Duration of response (DoR), determined by blinded central independent review
timeFrame: up to 53 months
measure: PFS determined by blinded central independent review
timeFrame: up to 53 months
measure: Bi-compartmental PFS, determined by blinded central independent review
timeFrame: up to 53 months
measure: OR determined by blinded central independent review
timeFrame: up to 53 months
measure: Change from baseline to Week 25 in the NSCLC-SAQ pain domain score
timeFrame: at baseline, at week 25
measure: Change from baseline to Week 25 in the NSCLC-SAQ dyspnea domain score
timeFrame: at baseline, at week 25
measure: Change from baseline to Week 25 in the NSCLC-SAQ cough domain score
timeFrame: at baseline, at week 25
measure: Change from baseline to Week 25 in the NSCLC-SAQ appetite domain score
timeFrame: at baseline, at week 25
measure: Change from baseline to Week 25 in the NSCLC-SAQ fatigue domain score
timeFrame: at baseline, at week 25
measure: Change from baseline to Week 25 in the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) physical functioning domain score
timeFrame: at baseline, at week 25
measure: Occurrence of adverse events (AEs) during the on-treatment period, graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0
timeFrame: up to 53 months
measure: Occurrence of serious AEs (SAEs) during the on-treatment period, graded according to CTCAE version 5.0
timeFrame: up to 53 months
Other outcomes:
Locations:
city: Huntsville
country: United States
facility: Clearview Cancer Institute
state: Alabama
city: Bullhead City
country: United States
facility: Mohtaseb Cancer Center and Blood Disorders, LLC
state: Arizona
city: Beverly Hills
country: United States
facility: Precision NextGen Oncology
state: California
city: Fresno
country: United States
facility: ClinRé 001-022 (Premier Cancer Care and Infusion Center)
state: California
city: Glendale
country: United States
facility: OPN Healthcare, Inc.
state: California
city: La Jolla
country: United States
facility: Scripps Green Hospital
state: California
city: Los Angeles
country: United States
facility: Valkyrie Clinical Trials
state: California
city: Bridgeton
country: United States
facility: St. Louis Cancer Care, LLP
state: Missouri
city: Springfield
country: United States
facility: Oncology Hematology Associates
state: Missouri
city: Reno
country: United States
facility: Cancer Care Specialists
state: Nevada
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: Lake Success
country: United States
facility: Northwell Health
state: New York
city: Wilson
country: United States
facility: Regional Medical Oncology Center
state: North Carolina
city: Canton
country: United States
facility: Gabrail Cancer Center
state: Ohio
city: Rock Hill
country: United States
facility: Carolina Blood and Cancer Care Associates, PA
state: South Carolina
city: Nashville
country: United States
facility: SCRI Oncology Partners
state: Tennessee
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute
state: Utah
city: Fairfax
country: United States
facility: Virginia Cancer Specialists, PC
state: Virginia
city: Edmonds
country: United States
facility: Swedish Cancer Institute
state: Washington
city: Issaquah
country: United States
facility: Swedish Cancer Institute
state: Washington
city: Seattle
country: United States
facility: Swedish Cancer Institute
state: Washington
city: Caba
country: Argentina
facility: Clinica Adventista Belgano
city: Ciudad Autónoma de Bs As
country: Argentina
facility: Instituto Medico Especializado Alexander Fleming
city: Córdoba
country: Argentina
facility: Instituto Oncologico de Cordoba
city: La Rioja
country: Argentina
facility: Centro Oncologico Riojano Integral (CORI)
city: Rosario
country: Argentina
facility: Instituto Médico de la Fundación Estudios Clínicos
city: Viedma
country: Argentina
facility: Clinicas Viedma S.A.
city: Randwick
country: Australia
facility: Prince of Wales Hospital-Randwick-66496
state: New South Wales
city: St Leonards
country: Australia
facility: Royal North Shore Hospital-St Leonards-20807
state: New South Wales
city: Woolloongabba
country: Australia
facility: Princess Alexandra Hospital
state: Queensland
city: Heidelberg
country: Australia
facility: Austin Health
state: Victoria
city: Subiaco
country: Australia
facility: St John of God Subiaco Hospital
state: Western Australia
city: Krems an der Donau
country: Austria
facility: Krems University Hospital
city: Vienna
country: Austria
facility: Clinic Floridsdorf
city: Anderlecht
country: Belgium
facility: Brussels - HOSP Jules Bordet
city: Gent
country: Belgium
facility: UNIV UZ Gent
city: Leuven
country: Belgium
facility: UZ Leuven
city: Bento Goncalves
country: Brazil
facility: Associacao Dr. Bartholomeu Tacchini
city: Londrina
country: Brazil
facility: Hospital do Cancer de Londrina
city: Porto Alegre
country: Brazil
facility: Hospital Sao Lucas da PUCRS
city: Rio de Janeiro
country: Brazil
facility: OncoClinicas Rio de Janeiro
city: Santo André
country: Brazil
facility: CEPHO - Centro de Estudos e Pesquisas em Hematologia e Oncologia
city: Sao Paulo
country: Brazil
facility: ICESP - Instituto do Cancer do Estado de Sao Paulo
city: São José do Rio Preto
country: Brazil
facility: Fundação Faculdade Regional de Medicina de São José do Rio Preto
city: Recoleta
country: Chile
facility: Bradford Hill- Centro de Investigación Clínica
city: Beijing
country: China
facility: Cancer Hospital of Chinese Academy of Medical Science
city: Beijing
country: China
facility: Beijing Cancer Hospital
city: Chengdu
country: China
facility: West China Hospital
city: Fuzhou
country: China
facility: Fujian Cancer Hospital
city: Guangzhou
country: China
facility: Guangdong Provincial People's Hospital
city: Hangzhou
country: China
facility: The First Affiliated Hospital, Zhejiang University
city: Hangzhou
country: China
facility: Sir Run Run Shaw Hospital, Zhejiang University, School of Medicine
city: Hangzhou
country: China
facility: Zhejiang Cancer Hospital
city: Harbin
country: China
facility: Harbin Medical University Cancer Hospital
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
city: Shanghai
country: China
facility: Zhongshan Hospital Affiliated to Fudan University
city: Taizhou
country: China
facility: Taizhou Hospital of Zhejiang Province
city: Wenzhou
country: China
facility: The First Affiliated Hospital of Wenzhou Med College
city: Wuhan
country: China
facility: Wuhan Union Hospital
city: Xiamen
country: China
facility: First Affiliated Hospital of Xiamen University
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
city: Bron
country: France
facility: HOP Louis Pradel
city: Lyon
country: France
facility: CTR Leon Berard
city: Marseille
country: France
facility: HOP Nord
city: Paris
country: France
facility: HOP Tenon
city: Paris
country: France
facility: INS Curie
city: Rennes
country: France
facility: HOP Pontchaillou
city: Strasbourg
country: France
facility: HOP Civil
city: Toulouse
country: France
facility: INS Claudius Regaud IUCT-Oncopole
city: Villejuif
country: France
facility: INS Gustave Roussy
city: Augsburg
country: Germany
facility: Universitätsklinikum Augsburg
city: Berlin
country: Germany
facility: Gemeinschaftskrankenhaus Havelhöhe gGmbH
city: Dresden
country: Germany
facility: Universitätsklinikum Carl Gustav Carus Dresden
city: Gießen
country: Germany
facility: Justus-Liebig Universität Gießen
city: Heidelberg
country: Germany
facility: Thoraxklinik-Heidelberg gGmbH am Universitätsklinikum Heidelberg
city: Köln
country: Germany
facility: Universitätsklinikum Köln (AöR)
city: Oldenburg
country: Germany
facility: Pius-Hospital, Oldenburg
city: Tübingen
country: Germany
facility: Universitätsklinikum Tübingen
city: Hong Kong
country: Hong Kong
facility: Queen Elizabeth Hospital-Hong Kong-51727
city: Hong Kong
country: Hong Kong
facility: Princess Margaret Hospital
city: Hong Kong
country: Hong Kong
facility: Queen Mary Hospital
city: Budapest
country: Hungary
facility: Koranyi National Institute For Pulmonolgy
city: Budapest
country: Hungary
facility: National Institute of Oncology
city: Deszk
country: Hungary
facility: Deszk Hospital of Chest Diseases
city: Farkasgyepu
country: Hungary
facility: Pulmonology Institute of Veszprem County, Farkasgyepu
city: Szekesfehervar
country: Hungary
facility: Fejer County Saint George University Teaching Hospital
city: Haifa
country: Israel
facility: Rambam Medical Center
city: Kfar-Saba
country: Israel
facility: Meir Medical Center
city: Petach Tikva
country: Israel
facility: Rabin Medical Center Beilinson
city: Tel Aviv
country: Israel
facility: Sourasky Medical Center
city: Bari
country: Italy
facility: Istituto Tumori Giovanni Paolo II
city: Candiolo (TO)
country: Italy
facility: Istituto Di Candiolo
city: Catania
country: Italy
facility: AOU Policlinico G. Rodolico San Marco
city: Napoli
country: Italy
facility: Istituto Nazionale IRCCS Tumori Fondazione Pascale
city: Parma
country: Italy
facility: Azienda Ospedaliera Unversitaria di Parma
city: Roma
country: Italy
facility: AOU Policlinico Umberto I
city: Varese
country: Italy
facility: A. O. Ospedale Circolo Fond. Macchi
city: Aichi, Nagoya
country: Japan
facility: Aichi Cancer Center Hospital
city: Aomori, Hirosaki
country: Japan
facility: Hirosaki University Hospital
city: Chiba, Kashiwa
country: Japan
facility: National Cancer Center Hospital East
city: Ehime, Matsuyama
country: Japan
facility: Shikoku Cancer Center
city: Fukuoka, Fukuoka
country: Japan
facility: Kyushu University Hospital
city: Hokkaido, Hakodate
country: Japan
facility: Hakodate Goryoukaku Hospital
city: Hokkaido, Sapporo
country: Japan
facility: Hokkaido Cancer Center
city: Ishikawa, Kanazawa
country: Japan
facility: Kanazawa University Hospital
city: Kanagawa, Kawasaki
country: Japan
facility: St. Marianna University Hospital
city: Kanagawa, Yokohama
country: Japan
facility: Kanagawa Cancer Center
city: Kyoto, Kyoto
country: Japan
facility: University Hospital Kyoto Prefectural University of Medicine
city: Miyagi, Sendai
country: Japan
facility: Tohoku University Hospital
city: Okayama, Okayama
country: Japan
facility: Okayama University Hospital
city: Osaka, Osaka
country: Japan
facility: Osaka International Cancer Institute
city: Shizuoka, Sunto-gun
country: Japan
facility: Shizuoka Cancer Center
city: Tokyo, Bunkyo-ku
country: Japan
facility: Juntendo University Hospital
city: Tokyo, Bunkyo-ku
country: Japan
facility: Komagome Hospital
city: Tokyo, Chuo-ku
country: Japan
facility: National Cancer Center Hospital
city: Tokyo, Koto-ku
country: Japan
facility: Japanese Foundation for Cancer Research
city: Wakayama, Wakayama
country: Japan
facility: Wakayama Medical University Hospital
city: Cheongiu
country: Korea, Republic of
facility: Chungbuk National University Hospital
city: Goyang
country: Korea, Republic of
facility: National Cancer Center
city: Incheon
country: Korea, Republic of
facility: Gachon University Gil Medical Center
city: Seoul
country: Korea, Republic of
facility: Kangbuk Samsung Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Suwon
country: Korea, Republic of
facility: The Catholic University of Korea, St.Vincent's Hospital
city: Ciudad de Mexico
country: Mexico
facility: Health Pharma Professional Research S.A. de C.V.
city: Mexico
country: Mexico
facility: Centro Oncologico Personalizado
city: Mexico
country: Mexico
facility: Instituto Nacional de Cancerologia
city: Veracruz
country: Mexico
facility: FAICIC S de RL de C.V.
city: Amsterdam
country: Netherlands
facility: Nederlands Kanker Instituut - Antoni van Leeuwenhoek Amsterdam (METC AVL)
city: Maastricht
country: Netherlands
facility: Maastricht University
city: Drammen
country: Norway
facility: Vestre Viken HF, Drammen Sykehus
city: Oslo
country: Norway
facility: Oslo Universitetssykehus HF, Radiumhospitalet
city: Lodz
country: Poland
facility: Polish Mother's Memorial Hospital - Research Institute
city: Poznan
country: Poland
facility: Greater Poland Center of Pulmonology and Thoracic Surgery
city: Poznan
country: Poland
facility: MED POLONIA SP Z O O, Clinical Trials Department,Poznan
city: Warsaw
country: Poland
facility: Oncology Center-Maria Sklodowska-Curie Institute
city: Lisboa
country: Portugal
facility: Hospital CUF Tejo
city: Lisboa
country: Portugal
facility: Centro Hospitalar Lisboa Norte Hospital Pulido Valente
city: Porto
country: Portugal
facility: Hospital CUF Porto
city: Rio Piedras
country: Puerto Rico
facility: Pan American Center for Oncology Trials, LLC
city: Singapore
country: Singapore
facility: National University Hospital-Singapore-22806
city: Singapore
country: Singapore
facility: National Cancer Centre Singapore
city: A Coruña
country: Spain
facility: Hospital A Coruña
city: Alicante
country: Spain
facility: Hospital General Universitario de Alicante
city: Barcelona
country: Spain
facility: Hospital Santa Creu i Sant Pau
city: Barcelona
country: Spain
facility: Hospital Vall d'Hebron
city: Bilbao
country: Spain
facility: Hospital de Basurto
city: L'Hospitalet de Llobregat
country: Spain
facility: Hospital Duran i Reynals
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañón
city: Madrid
country: Spain
facility: Hospital Ramón y Cajal
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Madrid
country: Spain
facility: Hospital La Paz
city: Málaga
country: Spain
facility: Hospital Regional Universitario de Málaga
city: Sevilla
country: Spain
facility: Hospital Virgen del Rocío
city: Valencia
country: Spain
facility: Hospital Clínico de Valencia
city: Göteborg
country: Sweden
facility: Sahlgrenska Universitetsjukhuset
city: Stockholm
country: Sweden
facility: Karolinska Universitetssjukhuset Solna
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Chang Gung Memorial Hospital
city: Taichung
country: Taiwan
facility: Chung Shan Medical University Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Cancer Center
city: Taoyuan
country: Taiwan
facility: Chang Gung Memorial Hospital(Linkou)
city: Edinburgh
country: United Kingdom
facility: Western General Hospital
city: Leicester
country: United Kingdom
facility: Leicester Royal Infirmary
city: London
country: United Kingdom
facility: Guy's Hospital
city: London
country: United Kingdom
facility: The Royal Marsden Hospital, Chelsea
city: Sutton
country: United Kingdom
facility: The Royal Marsden Hospital, Sutton
Study officials:
References: