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)

NCT ID: NCT04886804

Last Updated: 2025-12-22

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1

Total Enrollment

554 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-07-02

Study Completion Date

2028-08-30

Brief Summary

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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.

Detailed Description

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Conditions

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Neoplasm Metastasis Non-Small Cell Lung Cancer

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Phase Ia - Dose escalation part

Consecutive cohorts of patients treated with escalating doses of BI 1810631 monotherapy.

Group Type EXPERIMENTAL

zongertinib

Intervention Type DRUG

zongertinib

Phase Ib - Dose expansion part: Cohort 1

Group Type EXPERIMENTAL

zongertinib

Intervention Type DRUG

zongertinib

Phase Ib - Dose expansion part: Cohort 2

Group Type EXPERIMENTAL

zongertinib

Intervention Type DRUG

zongertinib

Phase Ib - Dose expansion part: Cohort 3

Group Type EXPERIMENTAL

zongertinib

Intervention Type DRUG

zongertinib

Phase Ib - Dose expansion part: Cohort 4

Group Type EXPERIMENTAL

zongertinib

Intervention Type DRUG

zongertinib

Phase Ib - Dose expansion part: Cohort 5

Group Type EXPERIMENTAL

zongertinib

Intervention Type DRUG

zongertinib

Phase Ib - Dose expansion part: Cohort 6

Cohort only in the United States of America (USA)

Group Type EXPERIMENTAL

zongertinib

Intervention Type DRUG

zongertinib

Phase Ib - Dose expansion part: Cohort 7

Cohort only in Japan

Group Type EXPERIMENTAL

zongertinib

Intervention Type DRUG

zongertinib

Phase Ib - Dose expansion part: Cohort 8

Cohort only in the United States of America (USA)

Group Type EXPERIMENTAL

zongertinib

Intervention Type DRUG

zongertinib

Interventions

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zongertinib

zongertinib

Intervention Type DRUG

Other Intervention Names

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BI 1810631, Hernexeos®

Eligibility Criteria

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Inclusion Criteria

* 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 and 7) .
* 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.
* 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.


* Patients with a documented diagnosis of HER2 aberration: overexpression OR gene amplification OR non-synonymous somatic mutation OR gene rearrangement involving HER2 or Neuregulin 1 (NRG1)
* Patient who has failed conventional treatment or for whom no therapy of proven efficacy exists or who is not eligible for established treatment options. Patient must have exhausted, or not be a suitable candidate for, available treatment options known to prolong survival for their disease


* Non-squamous non-small cell lung cancer (NSCLC) patients with documented human epidermal growth factor receptor 2 (HER2) mutation in the tyrosine kinase domain (TKD) as per local lab results.
* Patient who had received, in the advanced/metastatic setting, at least one line of systemic therapy. Patients with non-squamous NSCLC harboring additionally genomic aberrations for which approved targeted therapy is available as standard of care.


* Non-squamous NSCLC patient with a documented HER2 mutation in the tyrosine kinase domain (TKD) as per local lab results.
* Treatment naïve for non-squamous NSCLC.


* NSCLC Patient with a documented HER2 mutation outside of the tyrosine kinase domain (TKD) as per local lab results or squamous NSCLC patient with mutation in the TKD as per local lab results.
* Patient who had received, in the advanced/metastatic setting, at least one line of systemic therapy. Patients with NSCLC harboring additionally genomic aberrations for which approved targeted therapy is available as standard of care.


* NSCLC patients with documented HER2 mutation in the TKD as per local lab results.
* NSCLC patients who are either treatment naïve or who had received any prior line of treatment, in the advanced/metastatic setting. Patients with NSCLC harboring additional genomic aberrations for which approved targeted therapy is available as standard of care.
* Patient with active brain metastases who are not eligible for immediate local therapy, as per investigator evaluation.


* Non-squamous NSCLC patients with documented HER2 mutation in the TKD as per local lab results.
* Patient should have received, in the advanced/metastatic setting, at least one line of systemic therapy that includes a platinum-based combination chemotherapy and should have been treated with previous HER2 directed antibody-drug conjugates (ADC) in the same advanced/metastatic setting and developed disease progression recurrence during or after completing this therapy. Patients with NSCLC harboring additional genomic aberrations for which approved targeted therapy is available as standard of care.


* Non-squamous NSCLC Patient with documented HER2 mutation in the TKD as per local lab results.
* Patient who had received, in the advanced/metastatic setting, at least one line of systemic therapy.
* Patient without active brain metastases or patient with active brain metastases who are not eligible for immediate local therapy, as per investigator evaluation.
* Patient who is not eligible for any other recruiting cohort.


* Non-squamous NSCLC patient with documented HER2 mutation in the TKD as per local lab results.
* Patient who had received, in the advanced/metastatic setting, at least one line of systemic therapy.
* Patient without active brain metastases or patient with active brain metastases who are not eligible for immediate local therapy, as per investigator evaluation.
* Patient who is not eligible for any other recruiting cohort.


* Treatment naïve for NSCLC
* NSCLC (adenocarcinoma or squamous) patient with documented HER2 mutation in the tyrosine kinase domain (TKD) or non-squamous NSCLC with a documented HER2 mutation in the non tyrosine kinase domain (non TKD) as per local lab results

Exclusion Criteria

* 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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Boehringer Ingelheim

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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University of Alabama at Birmingham

Birmingham, Alabama, United States

Site Status RECRUITING

Precision NextGen Oncology

Beverly Hills, California, United States

Site Status NOT_YET_RECRUITING

City of Hope-Duarte-56419

Duarte, California, United States

Site Status RECRUITING

City of Hope - Seacliff

Huntington Beach, California, United States

Site Status NOT_YET_RECRUITING

City of Hope-Irvine-69674

Irvine, California, United States

Site Status NOT_YET_RECRUITING

Valkyrie Clinical Trials

Los Angeles, California, United States

Site Status RECRUITING

University of California Irvine

Orange, California, United States

Site Status RECRUITING

University of California Davis

Sacramento, California, United States

Site Status RECRUITING

Georgetown University

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

Site Status RECRUITING

Holy Cross Hospital-Fort Lauderdale-57892

Fort Lauderdale, Florida, United States

Site Status RECRUITING

Winship Cancer Institute

Atlanta, Georgia, United States

Site Status RECRUITING

Hawaii Cancer Care - Honolulu

Honolulu, Hawaii, United States

Site Status RECRUITING

Laura & Isaac Perlmutter Cancer Center at NYU Langone Health

New York, New York, United States

Site Status RECRUITING

Duke University Medical Center

Durham, North Carolina, United States

Site Status RECRUITING

Cleveland Clinic

Cleveland, Ohio, United States

Site Status RECRUITING

Sarah Cannon Research Institute-Nashville-48456

Nashville, Tennessee, United States

Site Status RECRUITING

Mary Crowley Cancer Research Center

Dallas, Texas, United States

Site Status RECRUITING

The University of Texas MD Anderson Cancer Center

Houston, Texas, United States

Site Status RECRUITING

Virginia Cancer Specialists, PC

Fairfax, Virginia, United States

Site Status RECRUITING

Fred Hutchinson Cancer Research Center

Seattle, Washington, United States

Site Status RECRUITING

Macquarie University

Macquarie Park, New South Wales, Australia

Site Status ACTIVE_NOT_RECRUITING

Ordensklinikum Linz GmbH

Linz, , Austria

Site Status COMPLETED

Brussels - HOSP Jules Bordet

Anderlecht/Brussels-Capital, , Belgium

Site Status ACTIVE_NOT_RECRUITING

Beijing Cancer Hospital

Beijing, , China

Site Status ACTIVE_NOT_RECRUITING

Jilin Province Cancer Hospital

Changchun, , China

Site Status COMPLETED

The First Hospital of Jilin University

Changchun, , China

Site Status ACTIVE_NOT_RECRUITING

Fujian Cancer Hospital

Fuzhou, , China

Site Status ACTIVE_NOT_RECRUITING

Guangdong Provincial People's Hospital

Guangzhou, , China

Site Status ACTIVE_NOT_RECRUITING

The First Affiliated Hospital, Zhejiang University

Hangzhou, , China

Site Status ACTIVE_NOT_RECRUITING

Zhejiang Cancer Hospital

Hangzhou, , China

Site Status ACTIVE_NOT_RECRUITING

Harbin Medical University Cancer Hospital

Harbin, , China

Site Status ACTIVE_NOT_RECRUITING

The Affiliated Cancer Hospital, Guangxi Medical University

Nanning, , China

Site Status COMPLETED

Shanghai Chest Hospital

Shanghai, , China

Site Status COMPLETED

Wuhan Union Hospital

Wuhan, , China

Site Status ACTIVE_NOT_RECRUITING

Tongji Hospital Affiliated Tongji Medical College Huazhong University of S & T

Wuhan, , China

Site Status ACTIVE_NOT_RECRUITING

First Affiliated Hospital of Xiamen University

Xiamen, , China

Site Status COMPLETED

Henan Cancer Hospital

Zhengzhou, , China

Site Status ACTIVE_NOT_RECRUITING

The First Affiliated Hospital of Zhengzhou University

Zhengzhou, , China

Site Status ACTIVE_NOT_RECRUITING

HOP Louis Pradel

Bron, , France

Site Status ACTIVE_NOT_RECRUITING

CTR Leon Berard

Lyon, , France

Site Status ACTIVE_NOT_RECRUITING

HOP Timone

Marseille, , France

Site Status ACTIVE_NOT_RECRUITING

INS Curie

Paris, , France

Site Status ACTIVE_NOT_RECRUITING

HOP Pontchaillou

Rennes, , France

Site Status ACTIVE_NOT_RECRUITING

INS Gustave Roussy

Villejuif, , France

Site Status ACTIVE_NOT_RECRUITING

Universitätsklinikum Augsburg

Augsburg, , Germany

Site Status COMPLETED

Universitätsklinikum Köln (AöR)

Cologne, , Germany

Site Status ACTIVE_NOT_RECRUITING

Technische Universität Dresden

Dresden, , Germany

Site Status ACTIVE_NOT_RECRUITING

Justus-Liebig Universität Gießen

Giessen, , Germany

Site Status ACTIVE_NOT_RECRUITING

Pius-Hospital, Oldenburg

Oldenburg, , Germany

Site Status ACTIVE_NOT_RECRUITING

Prince of Wales Hospital-Hong Kong-20715

Hong Kong, , Hong Kong

Site Status ACTIVE_NOT_RECRUITING

Queen Mary Hospital

Hong Kong, , Hong Kong

Site Status ACTIVE_NOT_RECRUITING

Rambam Medical Center

Haifa, , Israel

Site Status COMPLETED

Meir Medical Center

Kfar Saba, , Israel

Site Status ACTIVE_NOT_RECRUITING

Sourasky Medical Center

Tel Aviv, , Israel

Site Status ACTIVE_NOT_RECRUITING

The Chaim Sheba Medical Center Tel HaShomer

Tel Litwinsky, , Israel

Site Status COMPLETED

Istituto Di Candiolo

Candiolo (TO), , Italy

Site Status RECRUITING

Istituto Nazionale IRCCS Tumori Fondazione Pascale

Napoli, , Italy

Site Status COMPLETED

Azienda Ospedaliera Unversitaria di Parma

Parma, , Italy

Site Status COMPLETED

National Cancer Center Hospital East

Chiba, Kashiwa, , Japan

Site Status RECRUITING

Shikoku Cancer Center

Ehime, Matsuyama, , Japan

Site Status RECRUITING

Hiroshima University Hospital

Hiroshima, Hiroshima, , Japan

Site Status RECRUITING

Osaka International Cancer Institute

Osaka, Osaka, , Japan

Site Status RECRUITING

Kindai University Hospital

Osaka, Sakai, , Japan

Site Status RECRUITING

Hamamatsu University Hospital

Shizuoka, Hamamatsu, , Japan

Site Status RECRUITING

National Cancer Center Hospital

Tokyo, Chuo-ku, , Japan

Site Status RECRUITING

Nederlands Kanker Instituut

Amsterdam, , Netherlands

Site Status ACTIVE_NOT_RECRUITING

Leids Universitair Medisch Centrum (LUMC)

Leiden, , Netherlands

Site Status ACTIVE_NOT_RECRUITING

Hospital CUF Porto

Porto, , Portugal

Site Status ACTIVE_NOT_RECRUITING

National University Hospital-Singapore-22806

Singapore, , Singapore

Site Status COMPLETED

National Cancer Centre Singapore

Singapore, , Singapore

Site Status COMPLETED

Chungbuk National University Hospital

Chungju, , South Korea

Site Status COMPLETED

Seoul National University Bundang Hospital

Seongnam, , South Korea

Site Status ACTIVE_NOT_RECRUITING

Severance Hospital

Seoul, , South Korea

Site Status ACTIVE_NOT_RECRUITING

Asan Medical Center

Seoul, , South Korea

Site Status ACTIVE_NOT_RECRUITING

Samsung Medical Center

Seoul, , South Korea

Site Status ACTIVE_NOT_RECRUITING

Hospital Universitari Vall D Hebron

Barcelona, , Spain

Site Status ACTIVE_NOT_RECRUITING

Hospital Duran i Reynals

L'Hospitalet de Llobregat, , Spain

Site Status ACTIVE_NOT_RECRUITING

Hospital General Universitario Gregorio Marañón

Madrid, , Spain

Site Status COMPLETED

Hospital Universitario 12 de Octubre

Madrid, , Spain

Site Status ACTIVE_NOT_RECRUITING

Hospital Virgen de la Victoria

Málaga, , Spain

Site Status ACTIVE_NOT_RECRUITING

Hospital Clinico Universitario De Valencia

Valencia, , Spain

Site Status ACTIVE_NOT_RECRUITING

Karolinska Universitetssjukhuset Solna

Stockholm, , Sweden

Site Status COMPLETED

The Royal Marsden Hospital, Chelsea

London, , United Kingdom

Site Status ACTIVE_NOT_RECRUITING

Hammersmith Hospital

London, , United Kingdom

Site Status ACTIVE_NOT_RECRUITING

The Royal Marsden Hospital, Sutton

Sutton, , United Kingdom

Site Status ACTIVE_NOT_RECRUITING

Countries

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United States Australia Austria Belgium China France Germany Hong Kong Israel Italy Japan Netherlands Portugal Singapore South Korea Spain Sweden United Kingdom

Central Contacts

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Boehringer Ingelheim

Role: CONTACT

Phone: 1-800-243-0127

Email: [email protected]

Additional US locations available on demand. Please contact for options.

Role: CONTACT

Phone: 1-800-243-0127

Facility Contacts

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Boehringer Ingelheim

Role: primary

Boehringer Ingelheim

Role: primary

Boehringer Ingelheim

Role: primary

Boehringer Ingelheim

Role: primary

Boehringer Ingelheim

Role: primary

Boehringer Ingelheim

Role: primary

Boehringer Ingelheim

Role: primary

Boehringer Ingelheim

Role: primary

Boehringer Ingelheim

Role: primary

Boehringer Ingelheim

Role: primary

Boehringer Ingelheim

Role: primary

Boehringer Ingelheim

Role: primary

Boehringer Ingelheim

Role: primary

Boehringer Ingelheim

Role: primary

Boehringer Ingelheim

Role: primary

Boehringer Ingelheim

Role: primary

Boehringer Ingelheim

Role: primary

Boehringer Ingelheim

Role: primary

Boehringer Ingelheim

Role: primary

Boehringer Ingelheim

Role: primary

Boehringer Ingelheim

Role: primary

Boehringer Ingelheim

Role: primary

Boehringer Ingelheim

Role: primary

Boehringer Ingelheim

Role: primary

Boehringer Ingelheim

Role: primary

Boehringer Ingelheim

Role: primary

Boehringer Ingelheim

Role: primary

Boehringer Ingelheim

Role: primary

References

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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.

Reference Type DERIVED
PMID: 40293180 (View on PubMed)

Heymach 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.

Reference Type DERIVED
PMID: 40030100 (View on PubMed)

Heymach 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.

Reference Type DERIVED
PMID: 36528522 (View on PubMed)

Related Links

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Other Identifiers

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2020-004563-47

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

2024-511246-39-00

Identifier Type: REGISTRY

Identifier Source: secondary_id

U1111-1312-5969

Identifier Type: REGISTRY

Identifier Source: secondary_id

1479-0001

Identifier Type: -

Identifier Source: org_study_id