Beamion BCGC-1: A Study to Find a Suitable Dose of Zongertinib Used Alone and in Combination With Other Treatments to Test Whether it Helps People With Different Types of HER2+ Cancer That Has Spread
Beamion BCGC-1: A Phase Ib Dose Escalation and Phase II Dose Optimization, Randomized, Open-label, Multicenter Trial of Oral Zongertinib (BI 1810631) Alone or in Combination With Other Agents for the Treatment of Patients With Advanced HER2+ Metastatic Breast Cancer (mBC), Metastatic Gastric, Gastroesophageal Junction, or Esophageal Adenocarcinoma (mGEAC), or Metastatic Colorectal Cancer (mCRC)
1 other identifier
interventional
768
10 countries
107
Brief Summary
This study is open to adults aged 18 years and older with different types of HER2+ cancer that has spread and cannot be removed by surgery. People can take part in this study if their tumours show HER2 aberrations and previous treatment was not successful. The purpose of this study is to find a suitable dose of zongertinib that people with different types of HER2+ cancer that has spread can tolerate best when taken together with trastuzumab deruxtecan (T-DXd), with trastuzumab emtansine (T-DM1), with trastuzumab and capecitabine, with zanidatamab, or with mFOLFOX6 (with or without trastuzumab). Another purpose is to check whether zongertinib alone and in combination with other treatments can make tumours shrink. Zongertinib inhibits HER2. HER2 causes cancer cells to grow. In this study, participants receive treatment in cycles. Study participants are treated with zongertinib alone or in combination with other treatments. This study has 2 parts. In Part 1, participants in different groups receive increasing doses of zongertinib. In Part 2, participants are put into different groups by chance. Each group receives a different dose of zongertinib. Every participant has an equal chance of being in each group. During the study, the participants visit the study site regularly. In this study, researchers want to find the highest dose of zongertinib that participants can tolerate when taken together with other treatments. To find this out, researchers look at certain severe health problems that a number of participants have. The doctors regularly check the size of the tumour with imaging methods (CT/MRI) during the study. The doctors also regularly check participants' health and take note of any unwanted effects.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Jun 2024
Longer than P75 for phase_1
107 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
March 15, 2024
CompletedFirst Posted
Study publicly available on registry
March 21, 2024
CompletedStudy Start
First participant enrolled
June 3, 2024
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 8, 2029
ExpectedStudy Completion
Last participant's last visit for all outcomes
January 8, 2029
April 15, 2026
April 1, 2026
4.6 years
March 15, 2024
April 14, 2026
Conditions
Outcome Measures
Primary Outcomes (2)
Dose escalation (Phase Ib): Occurrence of dose-limiting toxicities (DLTs) in the maximum tolerated dose (MTD) evaluation period
The MTD evaluation period is defined as the first 21 days of the first treatment cycle for Cohorts A, B, C, G, K, and O. The MTD evaluation period is defined as the first 28 days after the first administration of any trial medication for Cohorts M and N.
up to 21 days
Dose optimization and justification (Phase II): Objective response (OR)
Objective response (OR) is defined as the best overall response of confirmed complete response (CR) or confirmed partial response (PR) according to RECIST 1.1 from the date of treatment start until the earliest date of disease progression, death, or last evaluable tumor assessment before start of subsequent anti-cancer therapy, or treatment discontinuation as assessed by investigator review.
up to 50 months
Secondary Outcomes (13)
Dose escalation (Phase Ib): Objective response (OR)
up to 50 months
Dose escalation (Phase Ib): Occurrence of dose-limiting toxicities (DLTs) during the entire treatment period
up to 50 months
Dose escalation (Phase Ib): Maximum measured concentration of zongertinib (at steady state) (Cmax,(ss))
up to 2 days
Dose escalation (Phase Ib): Area under the concentration-time curve of zongertinib over the time interval from 0 to 4h at steady state (AUC0-4h,ss)
up to 2 days
Dose escalation (Phase Ib): Area under the concentration-time curve of zongertinib over the time interval from 0 to the last quantifiable data point at steady state (AUC0-tz,ss)
up to 2 days
- +8 more secondary outcomes
Study Arms (18)
Phase Ib - Cohort A: zongertinib + Trastuzumab emtansine
EXPERIMENTALDose escalation (Phase Ib)
Phase Ib - Cohort B: zongertinib + Trastuzumab deruxtecan
EXPERIMENTALDose escalation (Phase Ib)
Phase Ib - Cohort C: zongertinib + Trastuzumab deruxtecan
EXPERIMENTALDose escalation (Phase Ib)
Phase II - Cohort D: zongertinib + Trastuzumab emtansine
EXPERIMENTALDose optimization (Phase II).
Phase II - Cohort E: zongertinib + Trastuzumab deruxtecan
EXPERIMENTALDose optimization (Phase II).
Phase II - Cohort F: zongertinib + Trastuzumab deruxtecan
EXPERIMENTALDose optimization (Phase II).
Phase Ib - Cohort G: zongertinib + trastuzumab + capecitabine
EXPERIMENTALDose escalation (Phase Ib)
Phase Ib - Cohort K: zongertinib + trastuzumab
EXPERIMENTALDose escalation (Phase Ib)
Phase II - Cohort H: zongertinib + trastuzumab + capecitabine
EXPERIMENTALDose optimization (Phase II).
Phase II - Cohort I: zongertinib
EXPERIMENTALDose optimization (Phase II).
Phase II - Cohort J: zongertinib + trastuzumab
EXPERIMENTALDose optimization (Phase II).
Phase II - Cohort I-ext: zongertinib
EXPERIMENTALExtension Phase II
Phase II - Cohort J-ext: zongertinib + trastuzumab
EXPERIMENTALExtension Phase II
Phase Ib - Cohort M: zongertinib + mFOLFOX6
EXPERIMENTALDose escalation (Phase Ib)
Phase Ib - Cohort N: zongertinib + trastuzumab + mFOLFOX6
EXPERIMENTALDose escalation (Phase Ib)
Phase Ib - Cohort O: zongertinib + zanidatamab
EXPERIMENTALDose escalation (Phase Ib) - is not conducted in China or South Korea
Phase II - Cohort L: zongertinib + trastuzumab
EXPERIMENTALDose justification (Phase II)
Phase II - Cohort L-ext: zongertinib + trastuzumab
EXPERIMENTALExtension Phase II
Interventions
Zongertinib
Herceptin®
Trastuzumab deruxtecan
Trastuzumab emtansine
Xeloda®
mFOLFOX6
Eligibility Criteria
You may qualify if:
- 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 informed consent form (ICF)
- Cohorts A to K and Cohort O: Documented Human epidermal growth factor receptor 2 overexpressing and/or amplified (HER2+), metastatic breast cancer (mBC) or metastatic gastric adenocarcinoma, gastroesophageal junction adenocarcinoma, or esophageal adenocarcinoma (mGEAC).
- Cohorts L (L-ext), M, and N (metastatic colorectal cancer (mCRC)): Documented Human epidermal growth factor receptor 2 (HER2) overexpression/amplification according to American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) gastric cancer guidelines and according to the result of local testing.
- For dose optimization and justification (Phase II): Patient must provide tumor tissue from locations not radiated prior to biopsy, if possible, collected through archival tissue
- History of prior treatment lines in palliative setting:
- For cohorts A, B, C, D, E, F, G, H, I, I-ext, J, J-ext, K and O documented investigator assessed progression after HER2-directed treatment for unresectable locally advanced or metastatic disease (For Cohorts D, H, I (I-ext), J (J-ext) - patients must have been pretreated with trastuzumab deruxtecan (T-DXd) and have progressed or have been intolerant to previous T-DXd).
- For cohorts L, L-ext, M and N documented progression or recurrence of disease during or following their latest line of therapy. Patients must have had at least one prior line of therapy for locally advanced unresectable disease or metastatic disease (adjuvant and neoadjuvant therapy excluded) and documented disease progression or recurrence of disease during or following their latest line of therapy. In the opinion of the Investigator, patients must be unlikely to tolerate or derive clinically meaningful benefit from further standard of care therapy known to prolong survival.
- Presence of at least one measurable lesion according to RECIST 1.1
- Eastern Cooperative Oncology Group (ECOG) score of 0 or 1
You may not qualify if:
- Previous treatment with:
- Any small molecule HER2 inhibitor in the palliative setting in Cohorts D, E, F, H, L, L-ext, M, and N. In Cohort D allowed in up to 15 patients in each dose level (DL).
- T-DXd in Cohorts E and F. In Cohort E allowed in up to 15 patients in each DL.
- trastuzumab emtansine (T-DM1) in the palliative setting in Cohort D and H. In Cohort H allowed in up to 15 patients in each DL.
- Capecitabine in Cohort D and H. In Cohort D allowed in up to 15 patients in each DL
- Presence of uncontrolled and/or symptomatic brain metastases, or leptomeningeal disease
- Mean resting corrected QT interval (QT interval corrected for heart rate by Fridericia´s formula (QTcF)) \>470 msec.
- Any factors that increase the risk of QT interval corrected for heart rate (QTc) prolongation or risk of arrhythmic events such as heart failure, hypokalemia, congenital long QT syndrome, personal or family history of long QT syndrome or unexplained sudden death under 40 years-of-age.
- Ejection fraction \<50% or the lower limit of normal of the institutional standard within 28 days prior to randomization
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (107)
Mayo Clinic-Arizona
Phoenix, Arizona, 85054, United States
The Oncology Institute of Hope and Innovation
Cerritos, California, 90703, United States
Ellison Medical Institute
Los Angeles, California, 90064, United States
Valkyrie Clinical Trials
Los Angeles, California, 90067, United States
University of California Los Angeles
Los Angeles, California, 90095, United States
University of California Irvine
Orange, California, 92868, United States
Sharp Memorial Hospital
San Diego, California, 92123, United States
Yale University School of Medicine
New Haven, Connecticut, 06510, United States
Mayo Clinic - Florida
Jacksonville, Florida, 32224, United States
H. Lee Moffitt Cancer Center and Research Institute
Tampa, Florida, 33612, United States
Orchard Healthcare Research Inc.- Skokie
Skokie, Illinois, 60077, United States
Community Health Network
Indianapolis, Indiana, 46250, United States
University of Iowa Hospitals and Clinics
Iowa City, Iowa, 52242, United States
Massachusetts General Hospital
Boston, Massachusetts, 02114, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215, United States
University of Michigan
Ann Arbor, Michigan, 48109, United States
Mayo Clinic, Rochester
Rochester, Minnesota, 55905, United States
Memorial Sloan-Kettering Cancer Center
New York, New York, 10065, United States
Penn State Milton S. Hershey Medical Center
Hershey, Pennsylvania, 17033, United States
Avera Cancer Institute
Sioux Falls, South Dakota, 57105, United States
Baptist Cancer Center - Memphis
Memphis, Tennessee, 38120, United States
SCRI Oncology Partners
Nashville, Tennessee, 37203, United States
Tennessee Oncology, Pllc
Nashville, Tennessee, 37203, United States
The Methodist Hospital Research Institute
Houston, Texas, 77030, United States
The University of Texas MD Anderson Cancer Center
Houston, Texas, 77030, United States
Inova Schar Cancer Institute
Fairfax, Virginia, 22031, United States
Virginia Cancer Specialists, PC
Fairfax, Virginia, 22031, United States
Fred Hutchinson Cancer Research Center
Seattle, Washington, 98109, United States
Cliniques Universitaires Saint-Luc
Brussels, 1200, Belgium
Edegem - UNIV UZ Antwerpen
Edegem, 2650, Belgium
UZ Leuven
Leuven, 3000, Belgium
Hôpital Vivalia De Libramont
Libramont-Chevigny, 6800, Belgium
Centre Hospitalier Universitaire de Liège
Liège, 4000, Belgium
CHU UCL Namur
Namur, 5000, Belgium
Jilin Province Cancer Hospital
Changchun, 130012, China
The First Hospital of Jilin University
Changchun, 130021, China
Sir Run Run Shaw Hospital, Zhejiang University, School of Medicine
Hangzhou, 310000, China
Harbin Medical University Cancer Hospital
Harbin, 150081, China
Jiangsu Province Hospital
Nanjing, 210029, China
Fudan University Shanghai Cancer Center
Shanghai, 200032, China
Tianjin Cancer Hospital
Tianjin, 300060, China
Henan Cancer Hospital
Zhengzhou, 450003, China
INS Bergonie
Bordeaux, 33000, France
CTR François Baclesse
Caen, 14076, France
CTR Georges-François Leclerc
Dijon, 21000, France
CTR Leon Berard
Lyon, 69008, France
INS Paoli-Calmettes
Marseille, 13273, France
HOP Tenon
Paris, 75020, France
CTR Eugène Marquis
Rennes, 35042, France
Institut de Cancérologie de l'Ouest
Saint-Herblain, 44800, France
Institut de Cancérologie de Strasbourg
Strasbourg, 67200, France
INS Claudius Regaud IUCT-Oncopole
Toulouse, 31059, France
Institut Gustave Roussy
Villejuif, 94805, France
Universitätsklinikum Carl Gustav Carus Dresden
Dresden, 01307, Germany
Universitätsklinikum Erlangen
Erlangen, 91054, Germany
Evang. Kliniken Essen-Mitte gGmbh
Essen, 45136, Germany
Asklepios Kliniken GmbH & Co. KGaA
Hamburg, 22763, Germany
Universitätsklinikum Mannheim GmbH
Mannheim, 68167, Germany
Universitätsklinikum Ulm
Ulm, 89075, Germany
Istituto Di Candiolo
Candiolo (TO), 10060, Italy
Az.Osp. Universitaria "Ospedali Riuniti"
Foggia, 71122, Italy
Istituto Scientifico Romagnolo
Meldola (FC), 47014, Italy
Ospedale San Raffaele S.r.l.
Milan, 20132, Italy
Istituto Europeo di Oncologia
Milan, 20141, Italy
Humanitas Istituto Clinico Catanese S.p.A.
Misterbianco (CT), 95045, Italy
Istituto Nazionale IRCCS Tumori Fondazione Pascale
Naples, 80131, Italy
Istituto Clinico Humanitas
Rozzano, 20089, Italy
Aichi Cancer Center Hospital
Aichi, Nagoya, 464-8681, Japan
Tokai University Hospital
Isehara, 259-1193, Japan
Hakuaikai Sagara Hospital
Kagoshima, 892-0833, Japan
Kanagawa Cancer Center
Kanagawa, Yokohama, 241-8515, Japan
National Cancer Center Hospital East
Kashiwa-shi, 277-8577, Japan
Kyoto University Hospital
Kyoto, 606-8507, Japan
Osaka International Cancer Institute
Osaka, 541-8567, Japan
Japanese Foundation for Cancer Research
Tokyo, Koto-ku, 135-8550, Japan
CHA Bundang Medical Center
Seongnam-si, 13496, South Korea
Seoul National University Bundang Hospital
Seongnam-si, 13620, South Korea
Severance Hospital, Yonsei University Health System
Seoul, 03722, South Korea
Asan Medical Center
Seoul, 05505, South Korea
Korea University Anam Hospital
Seoul, 2841, South Korea
Seoul National University Hospital
Seoul, 3080, South Korea
The Catholic University of Korea, Seoul St.Mary's Hospital
Seoul, 6273, South Korea
Severance Hospital, Yonsei University Health System
Seoul, 6591, South Korea
Hospital Teresa Herrera
A Coruña, 15006, Spain
Hospital del Mar
Barcelona, 08003, Spain
Hospital Universitari Vall d'Hebron
Barcelona, 08035, Spain
Hospital Clínic de Barcelona
Barcelona, 08036, Spain
Hospital Duran i Reynals
L'Hospitalet de Llobregat, 8906, Spain
Hospital General Universitario Gregorio Marañón
Madrid, 28007, Spain
Clínica Universidad de Navarra - Madrid
Madrid, 28022, Spain
Fundación Jiménez Díaz
Madrid, 28040, Spain
Hospital Clínico San Carlos
Madrid, 28040, Spain
Hospital Universitario 12 de Octubre
Madrid, 28041, Spain
Hospital Universitario La Paz
Madrid, 28046, Spain
CIO Clara Campal
Madrid, 28050, Spain
Hospital Universitario Virgen De La Macarena
Seville, 41009, Spain
Instituto Valenciano de Oncología
Valencia, 46009, Spain
Velindre Cancer Centre
Cardiff, CF14 2TL, United Kingdom
St James's University Hospital
Leeds, LS9 7TF, United Kingdom
St Bartholomew's Hospital
London, EC1A 7BE, United Kingdom
University College Hospital
London, NW1 2BU, United Kingdom
Royal Free Hospital
London, NW3 2QG, United Kingdom
The Royal Marsden Hospital, London
London, SW3 6JJ, United Kingdom
The Christie Hospital
Manchester, M20 4BX, United Kingdom
Freeman Hospital
Newcastle upon Tyne, NE7 7DN, United Kingdom
Nottingham University Hospital
Nottingham, NG5 1PB, United Kingdom
The Royal Marsden Hospital, Sutton
Sutton, SM2 5PT, United Kingdom
Related Publications (1)
Hurvitz S, Simonelli M, Yarza R, Berz D, Kitano S, Del Conte G, Acosta Eyzaguirre D, Doger de Speville Uribe BG, Maier D, Erzen D, Aykut Yazgili S, Curigliano G, Deng T, Yan M, Zhang Q, Wang X, Nakayama I, Shitara K. Beamion BCGC-1: phase Ib/II trial of zongertinib for advanced HER2-positive breast or gastroesophageal cancers. Future Oncol. 2025 Nov;21(26):3385-3393. doi: 10.1080/14796694.2025.2569553. Epub 2025 Oct 17.
PMID: 41108088DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
March 15, 2024
First Posted
March 21, 2024
Study Start
June 3, 2024
Primary Completion (Estimated)
January 8, 2029
Study Completion (Estimated)
January 8, 2029
Last Updated
April 15, 2026
Record last verified: 2026-04
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, CSR
- Time Frame
- One year after the approval has been granted by major Regulatory Authorities and after the primary manuscript has been accepted for publication, or after termination of the development program.
- Access Criteria
- For study documents - upon signing of a 'Document Sharing Agreement'. For study data - 1. after the submission and approval of the research proposal (checks will be performed by the sponsor and/or the independent review panel, including checking that the planned analysis does not compete with sponsor's publication plan); 2. and upon signing of a legal agreement.
Once the criteria in section "Time Frame" are fulfilled, researchers can use the following link https://www.clinicalstudies.boehringer-ingelheim.com/msw/datasharing to request access to the clinical study documents regarding this study, and upon a signed "Document Sharing Agreement". Furthermore, researchers can request access to the clinical study data, for this and other listed studies, after the submission of a research proposal and according to the terms outlined in the website.