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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Neoplasm Metastasis; Non-Small Cell Lung Cancer
• Intervention / Treatment: Drug: zongertinib

• Study Type: Interventional
• Enrollment (Actual): 608
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Macquarie Park, New South Wales, Australia, 2109
      • Macquarie University
• Austria
  • Linz, Austria, 4020
    • Ordensklinikum Linz GmbH
• Belgium
  • Anderlecht/Brussels-Capital, Belgium, 1070
    • Brussels - HOSP Jules Bordet
• China
  • Beijing, China, 100036
    • Beijing Cancer Hospital
  • Changchun, China, 130021
    • The First Hospital of Jilin University
  • Changchun, China, 130012
    • Jilin Province Cancer Hospital
  • Fuzhou, China, 350014
    • Fujian Cancer Hospital
  • Guangzhou, China, 510080
    • Guangdong Provincial People's Hospital
  • Hangzhou, China, 310022
    • Zhejiang Cancer Hospital
  • Hangzhou, China, 310003
    • The First Affiliated Hospital, Zhejiang University
  • Harbin, China, 150081
    • Harbin Medical University Cancer Hospital
  • Nanning, China, 530021
    • The Affiliated Cancer Hospital, Guangxi Medical University
  • Shanghai, China, 200030
    • Shanghai Chest Hospital
  • Wuhan, China, 430022
    • Wuhan Union Hospital
  • Wuhan, China, 430030
    • Tongji Hospital Affiliated Tongji Medical College Huazhong University of S & T
  • Xiamen, China, 361003
    • First Affiliated Hospital of Xiamen University
  • Zhengzhou, China, 450008
    • Henan Cancer Hospital
  • Zhengzhou, China, 450052
    • The First Affiliated Hospital of Zhengzhou University
• France
  • Bron, France, 69677
    • Hôpital Louis Pradel
  • Lyon, France, 69373
    • CTR Leon Berard
  • Marseille, France, 13385
    • HOP Timone
  • Paris, France, 75005
    • INS Curie
  • Rennes, France, 35000
    • HOP Pontchaillou
  • Villejuif, France, 94805
    • Institut Gustave Roussy
• Germany
  • Augsburg, Germany, 86156
    • Universitätsklinikum Augsburg
  • Cologne, Germany, 50937
    • Universitätsklinikum Köln (AöR)
  • Dresden, Germany, 01307
    • Technische Universität Dresden
  • Giessen, Germany, 35392
    • Justus-Liebig Universität Gießen
  • Oldenburg, Germany, 26121
    • Pius-Hospital, Oldenburg
• Hong Kong
  • Hong Kong, Hong Kong
    • Queen Mary Hospital
  • Hong Kong, Hong Kong, 999077
    • Prince of Wales Hospital-Hong Kong-20715
• Israel
  • Haifa, Israel, 3109601
    • Rambam Medical Center
  • Kfar Saba, Israel, 44281
    • Meir Medical Center
  • Tel Aviv, Israel, 6423906
    • Sourasky Medical Center
  • Tel Litwinsky, Israel, 52621
    • The Chaim Sheba Medical Center Tel HaShomer
• Italy
  • Candiolo (TO), Italy, 10060
    • Istituto di Candiolo
  • Naples, Italy, 80131
    • Istituto Nazionale IRCCS Tumori Fondazione Pascale
  • Parma, Italy, 43100
    • Azienda Ospedaliera Unversitaria di Parma
• Japan
  • Chiba, Kashiwa, Japan, 277-8577
    • National Cancer Center Hospital East
  • Ehime, Matsuyama, Japan, 791-0280
    • Shikoku Cancer Center
  • Hiroshima, Hiroshima, Japan, 734-8551
    • Hiroshima University Hospital
  • Osaka, Osaka, Japan, 541-8567
    • Osaka International Cancer Institute
  • Osaka, Sakai, Japan, 590-0197
    • Kindai University Hospital
  • Shizuoka, Hamamatsu, Japan, 431-3192
    • Hamamatsu University Hospital
  • Tokyo, Chuo-ku, Japan, 104-0045
    • National Cancer Center Hospital
• Netherlands
  • Amsterdam, Netherlands, 1066 CX
    • Nederlands Kanker Instituut
  • Leiden, Netherlands, 2333 ZA
    • Leids Universitair Medisch Centrum (LUMC)
• Portugal
  • Porto, Portugal, 4100-180
    • Hospital Cuf porto
• Singapore
  • Singapore, Singapore, 169610
    • National Cancer Centre Singapore
  • Singapore, Singapore, 119228
    • National University Hospital-Singapore-22806
• South Korea
  • Chungju, South Korea, 28644
    • Chungbuk National University Hospital
  • Seongnam, South Korea, 13620
    • Seoul National University Bundang Hospital
  • Seoul, South Korea, 05505
    • Asan Medical Center
  • Seoul, South Korea, 06351
    • Samsung Medical Center
  • Seoul, South Korea, 03722
    • Severance Hospital
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d'Hebron
  • L'Hospitalet de Llobregat, Spain, 08907
    • Hospital Duran i Reynals
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de octubre
  • Madrid, Spain, 28007
    • Hospital General Universitario Gregorio Marañon
  • Málaga, Spain, 29010
    • Hospital Universitario Virgen de la Victoria
  • Valencia, Spain, 46010
    • Hospital Clinico Universitario de Valencia
• Sweden
  • Stockholm, Sweden, 171 76
    • Karolinska Universitetssjukhuset Solna
• United Kingdom
  • London, United Kingdom, W12 0HS
    • Hammersmith Hospital
  • London, United Kingdom, SW3 6JJ
    • The Royal Marsden Hospital, Chelsea
  • Sutton, United Kingdom, SM2 5PT
    • The Royal Marsden Hospital, Sutton
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama at Birmingham
  • California
    • Beverly Hills, California, United States, 90212
      • Precision NextGen Oncology
    • Duarte, California, United States, 91010
      • City of Hope-Duarte-56419
    • Huntington Beach, California, United States, 92648
      • City of Hope - Seacliff
    • Irvine, California, United States, 92618
      • City of Hope-Irvine-69674
    • Los Angeles, California, United States, 90067
      • Valkyrie Clinical Trials
    • Orange, California, United States, 92868
      • University of California Irvine
    • Sacramento, California, United States, 95817
      • University of California Davis
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20007
      • Georgetown University
  • Florida
    • Fort Lauderdale, Florida, United States, 33308
      • Holy Cross Hospital-Fort Lauderdale-57892
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Winship Cancer Institute
  • Hawaii
    • Honolulu, Hawaii, United States, 96813
      • Hawaii Cancer Care - Honolulu
  • New York
    • New York, New York, United States, 10016
      • Laura & Isaac Perlmutter Cancer Center at NYU Langone Health
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Research Institute-Nashville-48456
  • Texas
    • Dallas, Texas, United States, 75230
      • Mary Crowley Cancer Research Center
    • Houston, Texas, United States, 77030
      • The University of Texas MD Anderson Cancer Center
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Virginia Cancer Specialists, PC
  • Washington
    • Seattle, Washington, United States, 98109
      • Fred Hutchinson Cancer Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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, 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.

Additional inclusion criteria for Phase Ia

• 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

Additional inclusion criteria for Phase Ib - Cohort 1 only

• 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.

Additional inclusion criteria for Phase Ib - Cohort 2 only

• 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.

Additional inclusion criteria for Phase Ib - Cohort 3 only

• 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.

Additional inclusion criteria for Phase Ib - Cohort 4 only

• 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.

Additional inclusion criteria for Phase Ib - Cohort 5 only

• 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.

Additional inclusion criteria for Phase Ib - Cohort 6 only

• 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.

Additional inclusion criteria for Phase Ib - Cohort 7 only

• 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.

Additional inclusion criteria for Phase Ib - Cohort 8 only

• 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

Additional inclusion criteria for Phase Ib - Cohort 9 only

• 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. Patients with NSCLC harboring additionally genomic aberrations for which approved targeted therapy is available as standard of care.

Further inclusion criteria apply.

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.

Further exclusion criteria apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

10

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase Ia - Dose escalation part; Consecutive cohorts of patients treated with escalating doses of BI 1810631 monotherapy.	Drug: zongertinib; zongertinib; Other Names: BI 1810631, Hernexeos®
Experimental: Phase Ib - Dose expansion part: Cohort 1	Drug: zongertinib; zongertinib; Other Names: BI 1810631, Hernexeos®
Experimental: Phase Ib - Dose expansion part: Cohort 2	Drug: zongertinib; zongertinib; Other Names: BI 1810631, Hernexeos®
Experimental: Phase Ib - Dose expansion part: Cohort 3	Drug: zongertinib; zongertinib; Other Names: BI 1810631, Hernexeos®
Experimental: Phase Ib - Dose expansion part: Cohort 4	Drug: zongertinib; zongertinib; Other Names: BI 1810631, Hernexeos®
Experimental: Phase Ib - Dose expansion part: Cohort 5	Drug: zongertinib; zongertinib; Other Names: BI 1810631, Hernexeos®
Experimental: Phase Ib - Dose expansion part: Cohort 6; Cohort only in the United States of America (USA)	Drug: zongertinib; zongertinib; Other Names: BI 1810631, Hernexeos®
Experimental: Phase Ib - Dose expansion part: Cohort 7; Cohort only in Japan	Drug: zongertinib; zongertinib; Other Names: BI 1810631, Hernexeos®
Experimental: Phase Ib - Dose expansion part: Cohort 8; Cohort only in the United States of America (USA)	Drug: zongertinib; zongertinib; Other Names: BI 1810631, Hernexeos®
Experimental: Phase Ib - Dose expansion part: Cohort 9; Cohort only in China	Drug: zongertinib; zongertinib; Other Names: BI 1810631, Hernexeos®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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: 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.
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.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Ib - Cohorts 1, 2 and 5: Duration of objective response (DoR) according to RECIST 1.1	DoR is defined as the time from first documented complete response (CR) or partial response (PR) until the earliest of disease progression or death among patients with objective response as assessed by central independent review.	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)	DC is defined as best overall response of complete response (CR) or partial response (PR) or stable disease (SD) where best overall response is defined according to RECIST version 1.1 as assessed central independent review, from first treatment administration until the earliest of disease progression, death or last evaluable tumor assessment before start of subsequent anti-cancer 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 1, 2 and 5: Progression-free survival (PFS)	PFS is defined as the time from first treatment administration until tumor progression according to RECIST version 1.1 as assessed by central independent review, or death from any cause, whichever occurs earlier.	From the start of the trial treatment until end of month 12, up to 12 months.
Phase Ib - Cohorts 1, 2 and 5: Objective response according to response assessment in neuro-oncology for brain metastases (RANO-BM) criteria as assessed by central independent review for patients with central nervous system (CNS) lesions at baseline		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 according to RANO-BM criteria as assessed by central independent review for patients with CNS lesions at baseline		From the start of the trial treatment until end of month 12, up to 12 months.
Phase Ib - Cohort 4: Duration of objective response (DoR) according to RANO-BM by central independent review		From the start of the trial treatment until end of month 12, up to 12 months.
Phase Ib - Cohort 4: Disease control (DC) according to RANO-BM by central independent review		From the start of the trial treatment until end of month 12, up to 12 months.
Phase Ib - Cohort 4: Progression-free survival (PFS) according to RANO-BM as assessed by central independent review		From the start of the trial treatment until end of month 12, up to 12 months.
Phase Ib - Cohort 4: OR according to RECIST 1.1 by central independent review		From the start of the trial treatment until end of month 12, up to 12 months.
Phase Ib - Cohort 4: Duration of OR according to RECIST 1.1 by central independent review		From the start of the trial treatment until end of month 12, up to 12 months.
Phase Ib - Cohort 4: PFS according to RECIST 1.1 as assessed by central independent review		From the start of the trial treatment until end of month 12, up to 12 months.
Phase Ib - All Cohorts: Number of patients experiencing DLTs during the entire treatment period		From the start of the trial treatment until end of month 12, up to 12 months.
Phase Ib - All Cohorts: Change from baseline to Day 1 of Cycle 5 in EORTC Core Quality of Life questionnaire (EORTC QLQ-C30) physical functioning domain score		Baseline and on Day 1 of Cycle 5 (each cycle is 21 days).
Phase Ib - All Cohorts: Change from baseline to Day 1 of Cycle 5 in Non-Small Cell Lung Cancer Symptom Assessment Questionnaire (NSCLC-SAQ) total score		Baseline and on Day 1 of Cycle 5 (each cycle is 21 days).
Phase Ib - All Cohorts: Change from baseline to Day 1 of Cycle 5 in EORTC item List 46 (IL46) score		Baseline and on Day 1 of Cycle 5 (each cycle is 21 days).
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 - All cohorts: Overall survival (OS), defined as time from first treatment administration until death from any cause		From the start of the trial treatment until end of month 12, up to 12 months.
Phase Ib - Cohorts 1, 2 and 5: Objective response according to RECIST 1.1 criteria as assessed by central independent review		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 according to RECIST 1.1 criteria as assessed by central independent review		From the start of the trial treatment until end of month 12, up to 12 months.
Phase Ib - Cohort 4: DoR according to RECIST 1.1 by central independent review		From the start of the trial treatment until end of month 12, up to 12 months.
Phase Ib - Cohort 4: PFS according to RECIST 1.1 by central independent review		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: Duration of 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 - Cohorts 3, 6, 7, 8 and 9: Disease control according to RECIST 1.1 as assessed by the investigator		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: Progression-free survival according to RECIST 1.1 as assessed by the investigator		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 RANO-BM criteria as assessed by the investigator for patients with CNS lesions at baseline		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: Disease control according to RANO-BM criteria as assessed by the investigator for patients with CNS lesions at baseline		From the start of the trial treatment until end of month 12, up to 12 months.
Phase Ib - Cohort 4: DC(1) according to RECIST 1.1 by central independent review		From the start of the trial treatment until end of month 12, up to 12 months.
Phase Ib - Cohort 4: DC(2) according to RECIST 1.1 by central independent review		From the start of the trial treatment until end of month 12, up to 12 months.

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• Heymach JV, Yamamoto N, Girard N, Ruiter G, Smit EF, Planchard D, Nadal E, Wu YL, Zugazagoitia J, Tu HY, Baik CS, Yoh K, Soo RA, Zhao Y, Sabari JK, Wermke M, Scheffler M, Ahn MJ, Fernamberg K, Schroeter L, Sadrolhefazi B, Thamer C, Eigenbrod-Giese S, Popat S; Beamion LUNG-1 Investigators. First-Line Zongertinib in Advanced HER2-Mutant Non-Small-Cell Lung Cancer. N Engl J Med. 2026 Apr 30;394(17):1675-1684. doi: 10.1056/NEJMoa2516969. Epub 2026 Apr 15.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): July 2, 2021
• Primary Completion (Estimated): December 30, 2026
• Study Completion (Estimated): August 30, 2028

Study Registration Dates

• First Submitted: May 4, 2021
• First Submitted That Met QC Criteria: May 12, 2021
• First Posted (Actual): May 14, 2021

Study Record Updates

• Last Update Posted (Actual): May 13, 2026
• Last Update Submitted That Met QC Criteria: May 12, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplastic Processes; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Pathological Conditions, Signs and Symptoms; Neoplasm Metastasis; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: 1479-0001; 2020-004563-47 (EudraCT Number); 2024-511246-39-00 (Registry Identifier: CTIS (EU)); U1111-1312-5969 (Registry Identifier: WHO International Clinical Trials Registry Platform (ICTRP))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

IPD Plan Description

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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No