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. 2025 Nov;21(26):3385-3393.
doi: 10.1080/14796694.2025.2569553. Epub 2025 Oct 17.

Beamion BCGC-1: phase Ib/II trial of zongertinib for advanced HER2-positive breast or gastroesophageal cancers

Sara Hurvitz  1 , Matteo Simonelli  2   3 , Ramón Yarza  4 , David Berz  5 , Shigehisa Kitano  6 , Gianluca Del Conte  7 , Daniel Acosta Eyzaguirre  8 , Bernard Gaston Doger de Speville Uribe  9 , Daniela Maier  10 , Damijan Erzen  10 , Sila Aykut Yazgili  11 , Giuseppe Curigliano  12   13 , Ting Deng  14 , Min Yan  15 , Qingyuan Zhang  16 , Xian Wang  17 , Izuma Nakayama  18 , Kohei Shitara  18
Affiliations

Beamion BCGC-1: phase Ib/II trial of zongertinib for advanced HER2-positive breast or gastroesophageal cancers

Sara Hurvitz et al. Future Oncol. 2025 Nov.

Abstract

Background: Overexpression and/or amplification of human epidermal growth factor receptor 2 (HER2) is a recognized oncogenic driver in metastatic breast cancer (mBC) and metastatic gastric, gastroesophageal junction, or esophageal adenocarcinomas (mGEAC). Although HER2-directed monoclonal antibodies, antibody - drug conjugates (ADCs), and tyrosine kinase inhibitors (TKIs) have revolutionized the treatment of HER2-positive tumors, additional combination regimens and/or novel agents are needed to expand sequential therapy options and improve patient outcomes - particularly following treatment with trastuzumab deruxtecan (T-DXd). Zongertinib is a novel, irreversible, HER2-selective TKI that spares EGFR.

Study design: Here, we detail the rationale and design of Beamion BCGC-1 (NCT06324357), an international Phase Ib/II open-label trial in which patients with previously treated HER2-positive mBC or mGEAC will receive zongertinib alone or in combination. Phase Ib (dose escalation) will determine the maximum tolerated dose of zongertinib plus trastuzumab emtansine (T-DM1), T-DXd, or trastuzumab ± capecitabine, in patients with HER2-positive mBC, and plus T-DXd in patients with HER2-positive mGEAC. Phase II (dose optimization) will assess two doses of zongertinib in combination regimens, or as monotherapy, in patients with mBC or mGEAC. The trial is actively recruiting in six countries globally.

Clinical trial registration: www.clinicaltrials.gov identifier is NCT06324357.

Keywords: HER2; Zongertinib; metastatic breast cancer; metastatic gastric, gastroesophageal junction, or esophageal adenocarcinoma; phase Ib/II clinical trial; trastuzumab; trastuzumab deruxtecan; trastuzumab emtansine.

Plain language summary

Patients with advanced cancer of the breast (mBC) or stomach/esophagus (mGEAC) may be treated with agents that target a specific protein called HER2 when their cancer overexpresses it. However, new and more effective HER2-targeted drugs are needed to give patients more options if the cancer returns, and to help reduce side effects from the cancer treatment. A new investigational drug, called zongertinib, is highly selective for HER2 and is expected to have fewer side effects than the currently available medications. This ongoing clinical trial is assessing whether zongertinib can be safely taken, either alone or with existing HER2-directed medicines, in patients with HER2-positive mBC or mGEAC who are no longer benefiting from standard treatment. The trial will also test whether zongertinib can effectively shrink tumors in these patients.

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Conflict of interest statement

S Hurvitz reports ownership of stock/shares with ROMTech (immediate family member); research funding has been received from Ambryx, Amgen Inc., Arvinas Inc., AstraZeneca/Daiichi Sankyo, Bayer AG, BioMarin Pharmaceutical Inc., Cascadian Therapeutics, CytomX Therapeutics, Daiichi Sankyo Co. Ltd., Dantari Inc., Dignitana AB, Eli Lilly and Company, G1 Therapeutics Inc., Genentech/Roche, Gilead Sciences Inc., Greenwich LifeSciences Inc., GlaxoSmithKline (GSK), Immunomedics Inc., Loxo Oncology/Eli Lilly and Company, MacroGenics Inc., Menarini Group, Merrimack Pharmaceuticals Inc., Novartis AG, Orinove Inc., Orum Therapeutics, Pfizer Inc., Phoenix Molecular Designs, Pieris Pharmaceuticals Inc., Puma Biotechnology Inc., Radius Health Inc., Samumed LLC, Sanofi, Seagen Inc., and Zymeworks Inc.; other potential financial relationships with (institutional disclosures) BeiGene Ltd., BriaCell Therapeutics Corp., BridgeBio Pharma Inc., Bristol Myers Squibb, Gilead Sciences Inc., InClin/Atossa Therapeutics Inc., Jazz Pharmaceuticals plc, Luminate, Mersana Therapeutics Inc., and Roche; and (personal disclosures) with Boehringer Ingelheim, Celcuity Inc., Embiosys, Medsir, Novartis AG, Pfizer Inc., and Roche. M Simonelli reports consulting fees have been received from Bristol Myers Squibb/Celgene, GlaxoSmithKline (GSK), Incyte Corporation, Naya Oncology, and Servier Laboratories; and other potential financial relationship include travel, accommodations, and expenses provided by Pfizer Inc., Roche, and Sanofi. R Yarza has served as principal investigator for AbbVie Inc., Ascendis Pharma A/S, Bayer AG, Boehringer Ingelheim, Duke Street Bio, Eikon Therapeutics Inc., Merck Serono, OnKure Inc., Pfizer Inc., Pyxis Oncology Inc., and Seagen Inc. D Berz reports employment with Valkyrie Clinical Trials; honoraria were received from EMD Serono, Jazz Pharmaceuticals, and Sun Pharma. Research funding was provided by Ascendis Pharma, Boehringer Ingelheim, BeiGene, BioNTech, Black Diamond Therapeutics, Bristol Myers Squibb, eFFECTOR Therapeutics, Faeth Therapeutics, G1 Therapeutics, Genprex, Hongyun Biotech, Incyte, InhibRx, Mirati Therapeutics, Seagen, Summit Therapeutics, WhiteOak, and Xencor; holds leadership roles with Jazz Pharmaceuticals and Sun Pharma; and travel, accommodations, and expenses were provided by EMD Serono and Jazz Pharmaceuticals. S Kitano reports receiving honoraria from AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Chugai Pharma, Daiichi Sankyo, Eisai, Eli Lilly Japan, GSK, Janssen, Merck KGaA, MSD, Novartis, Ono Pharmaceutical, Pfizer, Takeda, and Taiho Pharmaceutical; consulting fees were received from Astellas Pharma, AstraZeneca, Chugai Pharma, GSK, ImmuniT Research Inc., Kyowa Kirin, Ono Pharmaceutical, Rakuten Medical, Sumitomo Pharma, and United Immunity; research funding (institution) was provided by AbbVie, Astellas Pharma, AstraZeneca, Boehringer Ingelheim, Chugai Pharma, Daiichi Sankyo, Eisai, GSK, Incyte, Loxo/Eli Lilly, MSD, Ono Pharmaceutical, Pfizer, Takara Bio, and Takeda; and research funding (personal) from Kyowa Kirin and Merck KGaA. G Del Conte reports travel, accommodation, and expenses were provided by Daiichi Sankyo. B Doger de Speville Uribe is an employee of START Madrid Fundacion Jimenez Diaz; reports a non-financial interest as principal investigator for studies sponsored by AbbVie, Ascendis, Alterome Therapeutics, Artios, AstraZeneca, Bicycle, BioInvent, Boehringer, Corbus, Eikon, Enliven Therapeutics, Ipsen Pharma, Janssen, Merck, Nec Bio, Novartis, Revolution, Scorpion, Totus, and Zai Lab. D Maier is an employee of Boehringer Ingelheim Pharma GmbH & Co. KG. D Erzen is an employee of Boehringer Ingelheim. S Aykut Yazgili is an employee of Boehringer Ingelheim. G Curigliano has served on advisory councils or committees for Merck, AstraZeneca, Daiichi Sankyo, Lilly, Novartis, Pfizer, Gilead, Menarini, Bristol Myers Squibb, and Exact Sciences; has received consulting fees from Merck, AstraZeneca, Daiichi Sankyo, Lilly, Novartis, Pfizer, Gilead, Menarini, Bristol Myers Squibb, and Exact Sciences; and declares a non-financial conflict as President-Elect of ESMO. I Nakayama has received honoraria from Astellas Pharma, Bristol Myers Squibb, MSD, Ono Pharmaceutical, and Taiho Pharmaceutical; and has received research funding (institutional) from Boehringer Ingelheim, Chugai/Roche, Daiichi Sankyo/UCB Japan, MSD, Ono Pharmaceutical, and Astellas. K Shitara has received honoraria from Astellas Pharma, AstraZeneca, Bristol Myers Squibb, Eli Lilly, Janssen, and Ono Pharmaceutical; has received consulting fees from ALX Oncology, Amgen, Arcus Biosciences, Astellas Pharma, AstraZeneca, Bayer, Bristol Myers Squibb, Daiichi Sankyo, GSK K.K., Guardant Health, Healios, Janssen, Moderna Inc., MSD, Novartis, Ono Pharmaceutical, Takeda, and Zymeworks; and has received research funding (institutional) from Amgen, Astellas Pharma, AstraZeneca, Chugai Pharma, Daiichi Sankyo, Eisai, MSD, Ono Pharmaceutical, PPD-SNBL, PRA Health Sciences, Taiho Pharmaceutical, and Toray Industries. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. The authors received no direct compensation related to the development of the manuscript.

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Figures

Figure 1.
Figure 1.
Trial design of Beamion BCGC-1 (NCT06324357).
See this image and copyright information in PMC

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