Beamion LUNG-1: A Study to Test Different Doses of Zongertinib in People With Different Types of Advanced Cancer (Solid Tumours With Changes in the HER2 Gene)
Beamion LUNG-1: An Open Label, Phase I Dose Escalation Trial, With Dose Confirmation and Expansion, of Zongertinib (BI 1810631) as Monotherapy in Patients With Advanced or Metastatic Solid Tumors With HER2 Aberrations
4 other identifiers
interventional
608
17 countries
84
Brief Summary
The study has 2 parts. The first part is open to adults with different types of advanced cancer (solid tumours with changes in the HER2 gene) for whom previous treatment was not successful. The second part is open to people with non-small cell lung cancer with a specific mutation in the HER2 gene. The purpose of the first study part is to find the highest dose of a medicine called zongertinib the participants can tolerate. Once this dose is found, it will be used in the second study part to test whether zongertinib can make tumours shrink. In this study, zongertinib is given to people for the first time. Participants take zongertinib as tablets once a day or twice a day. The participants are in the study for as long as they benefit from and can tolerate treatment. Study doctors regularly check the participants' health and monitor the tumours. The doctors also take note of any unwanted effects that could have been caused by zongertinib.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Jul 2021
Longer than P75 for phase_1
84 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
May 4, 2021
CompletedFirst Posted
Study publicly available on registry
May 14, 2021
CompletedStudy Start
First participant enrolled
July 2, 2021
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 30, 2026
ExpectedStudy Completion
Last participant's last visit for all outcomes
August 30, 2028
March 13, 2026
March 1, 2026
5.5 years
May 4, 2021
March 12, 2026
Conditions
Outcome Measures
Primary Outcomes (5)
Phase Ia: Maximum Tolerated Dose (MTD)
Maximum tolerated dose is defined as the highest dose with less than 25% risk of the true Dose Limiting Toxicity (DLT) rate being equal to or above 33% during the MTD evaluation period in any studied regimen.
At the end of Cycle 1 (each cycle is 21 days).
Phase Ia: Number of patients with Dose Limiting Toxicities (DLTs) in the MTD evaluation period
At the end of Cycle 1 (each cycle is 21 days).
Phase Ib - Cohorts 1, 2 and 5 : Objective response (OR) as assessed by central independent review
OR is defined as best overall response of complete response (CR) or partial response (PR), where best overall response is determined according to Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1, from the first treatment administration until the earliest of disease progression, death or last evaluable tumor assessment before start of subsequent anticancer therapy, loss to follow-up or withdrawal of consent.
From the start of the trial treatment until end of month 12, up to 12 months.
Phase Ib - Cohorts 3, 6, 7, 8, and 9: Objective response according to RECIST 1.1 by investigator assessment
From the start of the trial treatment until end of month 12, up to 12 months.
Phase Ib: Cohort 4: Objective response according to Response Assessment in Neuro-Oncology for Brain Metastases (RANO-BM) by central independent review
From the start of the trial treatment until end of month 12, up to 12 months.
Secondary Outcomes (30)
Phase Ia: Number of patients experiencing DLTs during the entire treatment period
From the start of the trial treatment until end of month 8, up to 8 months.
Phase Ia: Maximum measured concentration of zongertinib in plasma (Cmax)
On day 1 and on day 15 of Cycle 1 (each cycle is 21 days).
Phase Ia: Area under the concentration-time curve of zongertinib in plasma (AUC0-t2)
On day 1 and on day 15 of Cycle 1 (each cycle is 21 days).
Phase Ib - Cohorts 1, 2 and 5: Duration of objective response (DoR) according to RECIST 1.1
From the start of the trial treatment until end of month 12, up to 12 months.
Phase Ib - Cohorts 1, 2 and 5: Disease control (DC)
From the start of the trial treatment until end of month 12, up to 12 months.
- +25 more secondary outcomes
Study Arms (10)
Phase Ia - Dose escalation part
EXPERIMENTALConsecutive cohorts of patients treated with escalating doses of BI 1810631 monotherapy.
Phase Ib - Dose expansion part: Cohort 1
EXPERIMENTALPhase Ib - Dose expansion part: Cohort 2
EXPERIMENTALPhase Ib - Dose expansion part: Cohort 3
EXPERIMENTALPhase Ib - Dose expansion part: Cohort 4
EXPERIMENTALPhase Ib - Dose expansion part: Cohort 5
EXPERIMENTALPhase Ib - Dose expansion part: Cohort 6
EXPERIMENTALCohort only in the United States of America (USA)
Phase Ib - Dose expansion part: Cohort 7
EXPERIMENTALCohort only in Japan
Phase Ib - Dose expansion part: Cohort 8
EXPERIMENTALCohort only in the United States of America (USA)
Phase Ib - Dose expansion part: Cohort 9
EXPERIMENTALCohort only in China
Interventions
zongertinib
Eligibility Criteria
You may qualify if:
- Histologically or cytologically confirmed diagnosis of an advanced, unresectable and/or metastatic non-haematologic malignancy. Patient must show presence of at least one measurable lesion according to Response Evaluation Criteria In Solid Tumors (RECIST) 1.1.
- Eastern Cooperative Oncology Group (ECOG) score of 0, 1 or 2 (ECOG=2 only for Cohorts 6, 7 and 9) .
- Availability and patient willingness to provide a sample of tumour for confirmation of the patient´s Human epidermal growth factor receptor 2 (HER2) status. This sample can be archival material obtained at any time prior to study enrollment.
- Patient willing and able to comply with the protocol requirements for tumour biopsies (biopsies from brain metastases are not allowed).
- Adequate organ function defined as all of the following:
- Absolute neutrophil count (ANC) ≥ 1.5 x 10\^9/L (≥ 1.5 x 10\^3/μL) (≥ 1500/mm\^3); haemoglobin ≥ 9.0 g/dL (≥ 90 g/L) (≥ 5.6 mmol/L); platelets ≥ 100 x 10\^9/L (100 x 10\^3/μL) (100 x 10\^3/mm3) without the use of hematopoietic growth factors within 4 weeks of start of trial medication.
- Total bilirubin ≤ 1.5 times the upper limit of normal (ULN), except for patients with Gilbert's syndrome: total bilirubin ≤ 3 x ULN or direct bilirubin ≤ 1.5 x ULN.
- Estimated Glomerular Filtration Rate (eGFR) ≥ 50 mL/min - calculated using Chronic Kidney Disease Epidemiology (CKD-EPI) formula (≥ 30 mL/min/1.73m² for cohorts 6, 8, and 9).
- Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3 x ULN if no demonstrable liver metastases, or otherwise ≤ 5 x ULN if transaminase elevation is attributable to liver metastases.
- Alkaline Phosphatase \< 5 x ULN.
- Recovered from any previous therapy-related toxicity to ≤ Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 at start of treatment (except for alopecia, stable sensory neuropathy and hypothyroidism (patients on thyroid replacement therapy) which must be ≤ CTCAE Grade 2)
- Life expectancy of at least 12 weeks at the start of treatment in the opinion of the investigator.
- At least 18 years of age at the time of consent or over the legal age of consent in countries where that is greater than 18 years.
- Signed and dated written informed consent in accordance with International Council on Harmonisation-Good Clinical Practice (ICH-GCP) and local legislation prior to admission to the trial.
- Male or female patients. Women of childbearing potential (WOCBP) and men who are able to father a child must be ready and able to use highly effective methods of birth control per International Council on Harmonisation (ICH) M3 (R2) that result in a low failure rate of less than 1% per year when used consistently and correctly.
- +25 more criteria
You may not qualify if:
- Major surgery (major according to the investigator's assessment) performed within 4 weeks prior to first trial treatment or planned within 6 months after screening
- Previous or concomitant malignancies other than the one treated in this trial within the last 2 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.
- Treatment with a systemic anti-cancer therapy or investigational drug within 21 days or 5 half-lives (whichever is shorter) of the first treatment with the study medication
- Patients who must or wish to continue the intake of restricted medication or any drug considered likely to interfere with the safe conduct of the trial
- Previous treatment with zongertinib.
- Radiotherapy within 2 weeks prior to first study treatment, except palliative radiotherapy to regions other than the chest, which is allowed up to 1 week prior to first study treatment.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (85)
University of Alabama at Birmingham
Birmingham, Alabama, 35233, United States
Precision NextGen Oncology
Beverly Hills, California, 90212, United States
City of Hope-Duarte-56419
Duarte, California, 91010, United States
City of Hope - Seacliff
Huntington Beach, California, 92648, United States
City of Hope-Irvine-69674
Irvine, California, 92618, United States
Valkyrie Clinical Trials
Los Angeles, California, 90067, United States
University of California Irvine
Orange, California, 92868, United States
University of California Davis
Sacramento, California, 95817, United States
Georgetown University
Washington D.C., District of Columbia, 20007, United States
Holy Cross Hospital-Fort Lauderdale-57892
Fort Lauderdale, Florida, 33308, United States
Winship Cancer Institute
Atlanta, Georgia, 30322, United States
Hawaii Cancer Care - Honolulu
Honolulu, Hawaii, 96813, United States
Laura & Isaac Perlmutter Cancer Center at NYU Langone Health
New York, New York, 10016, United States
Duke University Medical Center
Durham, North Carolina, 27710, United States
Cleveland Clinic
Cleveland, Ohio, 44195, United States
Sarah Cannon Research Institute-Nashville-48456
Nashville, Tennessee, 37203, United States
Mary Crowley Cancer Research Center
Dallas, Texas, 75230, United States
The University of Texas MD Anderson Cancer Center
Houston, Texas, 77030, United States
Virginia Cancer Specialists, PC
Fairfax, Virginia, 22031, United States
Fred Hutchinson Cancer Research Center
Seattle, Washington, 98109, United States
Macquarie University
Macquarie Park, New South Wales, 2109, Australia
Ordensklinikum Linz GmbH
Linz, 4020, Austria
Brussels - HOSP Jules Bordet
Anderlecht/Brussels-Capital, 1070, Belgium
Beijing Cancer Hospital
Beijing, 100036, China
Jilin Province Cancer Hospital
Changchun, 130012, China
The First Hospital of Jilin University
Changchun, 130021, China
Fujian Cancer Hospital
Fuzhou, 350014, China
Guangdong Provincial People's Hospital
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
The Affiliated Cancer Hospital, Guangxi Medical University
Nanning, 530021, China
Shanghai Chest Hospital
Shanghai, 200030, China
Wuhan Union Hospital
Wuhan, 430022, China
Tongji Hospital Affiliated Tongji Medical College Huazhong University of S & T
Wuhan, 430030, China
First Affiliated Hospital of Xiamen University
Xiamen, 361003, China
Henan Cancer Hospital
Zhengzhou, 450008, China
The First Affiliated Hospital of Zhengzhou University
Zhengzhou, 450052, China
Hôpital Louis Pradel
Bron, 69677, France
CTR Leon Berard
Lyon, 69373, France
HOP Timone
Marseille, 13385, France
INS Curie
Paris, 75005, France
HOP Pontchaillou
Rennes, 35000, France
Institut Gustave Roussy
Villejuif, 94805, France
Universitätsklinikum Augsburg
Augsburg, 86156, Germany
Universitätsklinikum Köln (AöR)
Cologne, 50937, Germany
Technische Universität Dresden
Dresden, 01307, Germany
Justus-Liebig Universität Gießen
Giessen, 35392, Germany
Pius-Hospital, Oldenburg
Oldenburg, 26121, Germany
Prince of Wales Hospital-Hong Kong-20715
Hong Kong, 999077, Hong Kong
Queen Mary Hospital
Hong Kong, Hong Kong
Rambam Medical Center
Haifa, 3109601, Israel
Meir Medical Center
Kfar Saba, 44281, Israel
Sourasky Medical Center
Tel Aviv, 6423906, Israel
The Chaim Sheba Medical Center Tel HaShomer
Tel Litwinsky, 52621, Israel
Istituto Di Candiolo
Candiolo (TO), 10060, Italy
Istituto Nazionale IRCCS Tumori Fondazione Pascale
Naples, 80131, Italy
Azienda Ospedaliera Unversitaria di Parma
Parma, 43100, Italy
National Cancer Center Hospital East
Chiba, Kashiwa, 277-8577, Japan
Shikoku Cancer Center
Ehime, Matsuyama, 791-0280, Japan
Hiroshima University Hospital
Hiroshima, Hiroshima, 734-8551, Japan
Osaka International Cancer Institute
Osaka, Osaka, 541-8567, Japan
Kindai University Hospital
Osaka, Sakai, 590-0197, Japan
Hamamatsu University Hospital
Shizuoka, Hamamatsu, 431-3192, Japan
National Cancer Center Hospital
Tokyo, Chuo-ku, 104-0045, Japan
Nederlands Kanker Instituut
Amsterdam, 1066 CX, Netherlands
Leids Universitair Medisch Centrum (LUMC)
Leiden, 2333 ZA, Netherlands
Hospital CUF Porto
Porto, 4100-180, Portugal
National University Hospital-Singapore-22806
Singapore, 119228, Singapore
National Cancer Centre Singapore
Singapore, 169610, Singapore
Chungbuk National University Hospital
Chungju, 28644, South Korea
Seoul National University Bundang Hospital
Seongnam, 13620, South Korea
Severance Hospital
Seoul, 03722, South Korea
Asan Medical Center
Seoul, 05505, South Korea
Samsung Medical Center
Seoul, 06351, South Korea
Hospital Universitari Vall D Hebron
Barcelona, 08035, Spain
Hospital Duran i Reynals
L'Hospitalet de Llobregat, 08907, Spain
Hospital General Universitario Gregorio Marañón
Madrid, 28007, Spain
Hospital Universitario 12 de Octubre
Madrid, 28041, Spain
Hospital Universitario Virgen de la Victoria
Málaga, 29010, Spain
Hospital Clinico Universitario de Valencia
Valencia, 46010, Spain
Karolinska Universitetssjukhuset Solna
Stockholm, 171 76, Sweden
The Royal Marsden Hospital, Chelsea
London, SW3 6JJ, United Kingdom
Hammersmith Hospital
London, W12 0HS, United Kingdom
The Royal Marsden Hospital, Sutton
Sutton, SM2 5PT, United Kingdom
Related Publications (3)
Heymach JV, Ruiter G, Ahn MJ, Girard N, Smit EF, Planchard D, Wu YL, Cho BC, Yamamoto N, Sabari JK, Zhao Y, Tu HY, Yoh K, Nadal E, Sadrolhefazi B, Rohrbacher M, von Wangenheim U, Eigenbrod-Giese S, Zugazagoitia J; Beamion LUNG-1 Investigators. Zongertinib in Previously Treated HER2-Mutant Non-Small-Cell Lung Cancer. N Engl J Med. 2025 Jun 19;392(23):2321-2333. doi: 10.1056/NEJMoa2503704. Epub 2025 Apr 28.
PMID: 40293180DERIVEDHeymach JV, Opdam F, Barve M, Tu HY, Wu YL, Berz D, Schroter L, Botilde Y, Sadrolhefazi B, Serra J, Yoh K, Yamamoto N. HER2-Selective Tyrosine Kinase Inhibitor, Zongertinib (BI 1810631), in Patients With Advanced/Metastatic Solid Tumors With HER2 Alterations: A Phase Ia Dose-Escalation Study. J Clin Oncol. 2025 Apr 10;43(11):1337-1347. doi: 10.1200/JCO-24-01727. Epub 2025 Mar 3.
PMID: 40030100DERIVEDHeymach J, Opdam F, Barve M, Gibson N, Sadrolhefazi B, Serra J, Yamamoto N. A Phase I, Open-Label, Dose Confirmation, Escalation, and Expansion Trial of BI 1810631 as Monotherapy in Patients With Advanced or Metastatic Solid Tumors With HER2 Aberrations. Clin Lung Cancer. 2023 Mar;24(2):e65-e68. doi: 10.1016/j.cllc.2022.10.008. Epub 2022 Nov 11.
PMID: 36528522DERIVED
Related Links
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 4, 2021
First Posted
May 14, 2021
Study Start
July 2, 2021
Primary Completion (Estimated)
December 30, 2026
Study Completion (Estimated)
August 30, 2028
Last Updated
March 13, 2026
Record last verified: 2026-03
Data Sharing
- IPD Sharing
- Will not share
Clinical studies sponsored by Boehringer Ingelheim, phases I to IV, interventional and non-interventional, are in scope for sharing of the raw clinical study data and clinical study documents. Exceptions might apply, e.g. studies in products where Boehringer Ingelheim is not the license holder; studies regarding pharmaceutical formulations and associated analytical methods, and studies pertinent to pharmacokinetics using human biomaterials; studies conducted in a single center or targeting rare diseases (in case of low number of patients and therefore limitations with anonymization). For more details refer to: https://www.clinicalstudies.boehringer-ingelheim.com/msw/datasharing