Ingelheim, Germany / Ridgefield, Connecticut, U.S.
- Data from the Phase Ib Beamion LUNG-1 trial evaluating zongertinib in treatment-naïve patients with advanced HER2 (ERBB2)-mutant NSCLC were presented for the first time at ESMO 2025.
- Confirmed response by blinded independent central review was 77%, with 96% of patients achieving disease control.1
- Zongertinib recently received Breakthrough Therapy Designations for first-line treatment by the U.S. FDA and China’s CDE.
Boehringer Ingelheim reported positive results from the Beamion LUNG-1 trial evaluating zongertinib in treatment-naïve patients (N=74) with advanced non-small cell lung cancer (NSCLC) who have HER2 (ERBB2) activating mutations in the tyrosine kinase domain (TKD). Zongertinib demonstrated efficacy with a confirmed objective response rate (ORR) of 77%. The data were featured at the European Society for Medical Oncology (ESMO) Congress 2025.
“Non-small cell lung cancer with HER2 activating mutations is a highly heterogeneous and aggressive disease which in the past has made it hard to find a targeted treatment offering significant clinical benefit,” said the presenting author, Prof. Sanjay Popat, MD, PhD, Consultant Medical Oncologist, Head of the Lung Unit, and Lead for the Lung Cancer Research Programme at the Royal Marsden Hospital. “A response rate of 77% regardless of mutation subtype and a median time to response of 1.4 months indicate that zongertinib elicited a rapid response in treatment-naïve patients with HER2 TKD-mutant NSCLC, making it a promising future targeted treatment option in this setting.”
Of the responders (77%), 8% of patients achieved complete response, 69% achieved partial response and 96% of patients achieved disease control. At data cut-off, median values for duration of response (DoR) and progression-free survival (PFS) were not yet mature, with 47% of patients remaining on treatment and encouraging 6-month rates for DoR of 80% and PFS of 79%.
Data presented at ESMO demonstrated a manageable safety profile for zongertinib in treatment-naïve patients, with a similar pattern of adverse events (AEs) to that observed and reported in previously treated patients. Adverse events led to dose reductions in 11 patients (15%) and dose discontinuations in 7 patients (9%). The most commonly reported AEs were grade 1 diarrhea and rash.
Zongertinib was recently granted Breakthrough Therapy Designation by the U.S. Food and Drug Administration (FDA) and the Center for Drug Evaluation (CDE) in China for the first-line treatment of adult patients with unresectable or metastatic NSCLC whose tumors have HER2 TKD activating mutations.
Beamion LUNG-2 (NCT06151574), a Phase III randomized study evaluating first-line zongertinib versus standard of care in patients with unresectable, locally advanced or metastatic HER2-mutant NSCLC, is currently enrolling.
“We see a significant unmet need in the first-line setting for patients with HER2-mutant advanced NSCLC, where there are currently no targeted treatments approved. These data are extremely encouraging and reinforce our belief in the potential of zongertinib for treatment-naïve patients with advanced non-small cell lung cancer with activating HER2 mutations,” said Shashank Deshpande, Chairman of the Board of Managing Directors and Head of Human Pharma at Boehringer Ingelheim. “Employing our dual approach to oncology, we are advancing both cancer cell and immune cell-directed therapies to pioneer breakthroughs for patients."
HER2 (ERBB2)-mutant NSCLC is a disease characterized by its aggressive nature and poor prognosis. Up to 4% of lung cancers are driven by HER2 (ERBB2) mutations (or gene alterations).2 Mutations in HER2 (ERBB2) can lead to overexpression and overactivation, which can in turn result in uncontrolled cell production, inhibition of cell death and promotion of tumor growth and spread.3
About non-small cell lung cancer (NSCLC)
Lung cancer claims more lives than any other cancer type4 and the incidence is set to increase to over 3 million cases worldwide by 2040.5 NSCLC is the most common type of lung cancer.4 The condition is often diagnosed at a late stage,6 and fewer than 3 in 10 patients are alive five years after diagnosis.6 People living with advanced NSCLC can experience a detrimental physical, psychological, and emotional impact on their daily lives.7,8,9 There remains a high unmet need for additional treatment options for people living with advanced NSCLC. Up to 4% of lung cancers are driven by HER2 (ERBB2) mutations (or gene alterations).2 Mutations in HER2 (ERBB2) can lead to overexpression and overactivation, which can in turn result in uncontrolled cell production, inhibition of cell death and promotion of tumor growth and spread.3
About zongertinib
Zongertinib is an irreversible tyrosine kinase inhibitor (TKI) that selectively inhibits HER2 (ERBB2) while sparing wild-type EGFR, thereby minimizing associated toxicities.
Zongertinib has been approved by the U.S. FDA as the first orally administered, targeted therapy for previously treated patients with HER2 (ERBB2)-mutant advanced NSCLC. The U.S. FDA also granted Breakthrough Therapy Designation for zongertinib for use in a first-line setting.
The therapy has been approved by China’s NMPA as monotherapy for the treatment of adult patients with unresectable, locally advanced or metastatic NSCLC whose tumors have activating HER2 (ERBB2) mutations and who have received at least one line of prior systemic therapy. China’s CDE also granted Breakthrough Therapy Designation for zongertinib for use in a first-line setting.
Zongertinib, a first-in-class oral targeted therapy for HER2 (ERBB2)-mutant NSCLC, received approval for manufacturing and marketing in Japan. This approval makes zongertinib the first oral molecularly targeted therapy available in Japan for previously treated, unresectable, advanced, or recurrent HER2 (ERBB2)-mutant NSCLC.
About the Beamion clinical trial program
Beamion LUNG-1 (NCT04886804): An open-label, Phase I dose escalation trial, with dose confirmation and expansion, of zongertinib as monotherapy in people with advanced or metastatic solid tumors and NSCLC with activating HER2 (ERRB2) alterations. The study has two parts. The first part is open to adults with different types of advanced cancer (solid tumors with changes in the HER2 (ERRB2) gene) for whom previous treatment was not successful. The second part is open to people with advanced NSCLC with a specific mutation in the HER2 (ERBB2) gene. Beamion LUNG-2 (NCT06151574) is a Phase III, open label, randomized, active-controlled study in patients with unresectable, locally advanced or metastatic non-squamous NSCLC harboring HER2 (ERBB2) TKD mutations to evaluate zongertinib compared with standard of care. The study will enroll 416 patients who will be randomly assigned to receive either zongertinib or standard of care treatment. Beamion LUNG-3 (NCT07195695) is an interventional Phase III, randomized, controlled, multi-center trial evaluating zongertinib as an adjuvant monotherapy compared with standard of care in patients with early-stage, resectable NSCLC that has HER2 TKD mutations. Its objective is to test whether zongertinib helps people with surgically removed, NSCLC with HER2 mutations compared with standard treatment and will enroll 400 patients.
About Boehringer Ingelheim in oncology
We have a clear aspiration – to transform the lives of people with cancer by delivering meaningful advances, with the ultimate goal of curing a range of cancers. Boehringer Ingelheim’s generational commitment to driving scientific innovation is reflected by the company’s robust pipeline of cancer cell-directed and immuno-oncology investigational therapies, as well as the smart combination of these approaches. Boehringer’s ambition in oncology is to take a diligent and broad approach, creating a collaborative research network to tap into a diversity of minds, which is vital in addressing some of the most challenging, but potentially most impactful, areas of cancer research. Simply put, for Boehringer Ingelheim, cancer care is personal, today and for generations. Read more at www.boehringer-ingelheim.com and www.boehringer-ingelheim.com/uk.
About Boehringer Ingelheim
Boehringer Ingelheim is a biopharmaceutical company active in both human and animal health. As one of the industry’s top investors in research and development, the company focuses on developing innovative therapies that can improve and extend lives in areas of high unmet medical need. Independent since its foundation in 1885, Boehringer takes a long-term perspective, embedding sustainability along the entire value chain. Our approximately 54,500 employees serve over 130 markets to build a healthier and more sustainable tomorrow. Learn more at www.boehringer-ingelheim.com and www.boehringer-ingelheim.com/uk.
References:
1 Popat S. et al. Zongertinib as first-line treatment in patients with advanced HER2-mutant NSCLC: Beamion LUNG 1. presented at ESMO, Berlin, 17-21 October, 2025.
2 Arcila, M. E. et al. Prevalence, clinicopathologic associations, and molecular spectrum of ERBB2 (HER2) tyrosine kinase mutations in lung adenocarcinomas. Clin. cancer Res. an Off. J. Am. Assoc. Cancer Res. 18, 4910–4918 (2012).
3 Galogre M, et al. A review of HER2 overexpression and somatic mutations in cancers, Critical Reviews in Oncology/Hematology, Volume 186, 2023, 103997.
4 Zeng J, Ma W, Young RB, Li T. Targeting HER2 genomic alterations in non-small cell lung cancer. J Natl Cancer Cent. 2021 May 3;1(2):58-73.
5 International Agency for Research on Cancer – World Health Organization. Rates of trachea, bronchus and lung cancer. Available at: https://gco.iarc.fr/tomorrow/en (Accessed: October 2025).
6 National Cancer Institute Surveillance, Epidemiology, and End Results (SEER). https://seer.cancer.gov/statfacts/html/lungb.html (Accessed: October 2025).
7 Valentine, T. R. et al. Illness Perceptions and Psychological and Physical Symptoms in Newly Diagnosed Lung Cancer. Health Psychol. 2022 Jun; 41(6): 379–388.
8 Andersen, B. L. et al. Newly diagnosed patients with advanced non-small cell lung cancer: A clinical description of those with moderate to severe depressive symptoms. Lung Cancer. 2020 Jul;145:195-204.
9 Presley, C. J. et al. Functional Disability Among Older Versus Younger Adults With Advanced Non–Small-Cell Lung Cancer. JCO Oncol Pract. 2021 May 3;17(6):e848–e858.
