FDA approves HERNEXEOS®, the first targeted therapy for adults with HER2-mutant advanced NSCLC as an initial treatment option

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This press release is not intended for UK media

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Ingelheim, Germany and Ridgefield, Conn. [DATE] — The U.S. Food and Drug Administration (FDA) approved Boehringer Ingelheim’s HERNEXEOS^® (zongertinib tablets) for the treatment of adult patients with advanced non-small cell lung cancer (NSCLC) whose tumors have HER2 (ERBB2) tyrosine kinase domain activating mutations, as detected by an FDA-authorized test.¹

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This indication is approved under accelerated approval based on objective response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.¹ Boehringer is currently enrolling patients in Beamion LUNG-2, a confirmatory Phase III trial evaluating zongertinib as a first-line treatment for this patient population. (NCT06151574).

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Accelerated approval is based on data from a cohort of treatment-naïve patients (N=72) in the Phase Ib Beamion LUNG-1 trial which demonstrated an objective response rate of 76%, including 11% of patients with a complete response and 65% of patients with a partial response.¹ Zongertinib demonstrated a duration of response of ≥6 months in 64% of patients.¹ This data builds upon the FDA accelerated approval of HERNEXEOS for previously treated patients in August 2025.

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“Zongertinib is setting a new standard as the first targeted therapy for treatment naïve patients with HER2-mutant advanced non-small cell lung cancer with demonstrated efficacy, a manageable safety profile, and once daily oral administration,” said coordinating investigator for the Beamion LUNG-1 trial, Dr. John Heymach, MD, PhD, chair of Thoracic/Head and Neck Medical Oncology at The University of Texas MD Anderson Cancer Center. “Now these patients finally have a targeted treatment option that they can receive immediately following identification of a HER2 mutation.”

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“With HERNEXEOS now approved for patients with HER2-mutant advanced NSCLC as an initial treatment option, we are delivering on our promise to transform care for people with this rare and aggressive cancer,” said Shashank Deshpande, Chairman of the Board of Managing Directors and Head of Human Pharma at Boehringer Ingelheim. “This approval marks a shift towards personalized care with a targeted treatment option for patients with HER2 mutated lung cancer. It underscores our relentless focus on accelerating innovation to address a significant unmet need.”

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HER2 (ERBB2) mutations occur in approximately 2-4% of NSCLC cases and are associated with a poor prognosis and higher incidence of brain metastases.^2,3,4 Alterations in the HER2 (ERBB2) gene, including mutations, amplification and overexpression, trigger uncontrolled cell proliferation, inhibiting cell death, and promoting tumor growth and spread.^2,4

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“We first learned about the HER2 genetic mutation as a lung cancer driver in a small subset of patients more than 20 years ago,” said Danielle Hicks, Chief Patient Officer of GO2 for Lung Cancer. “Half of these people do not respond to the current standard of care, which is why it is vital to provide them with a treatment option that has been designed specifically for their disease. Understanding your biomarkers is so important because it can unlock more personalized and effective treatment options.”

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Zongertinib demonstrated a manageable safety profile as an initial treatment that was consistent with that observed and reported in previously treated patients. Adverse events led to dose discontinuations in 6% of patients.¹ In a pooled safety population, which included 292 patients with HER2 (ERBB2)-mutant NSCLC, both treatment-naïve and previously treated, the most common (>20%) adverse reactions were diarrhea (54%), rash (28%), hepatotoxicity (27%), fatigue (25%), nausea (23%), musculoskeletal pain (21%), and upper respiratory tract infection (20%).¹

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The FDA granted zongertinib Breakthrough Therapy Designation for patients with HER2 (ERBB2)-mutant advanced NSCLC as an initial treatment. The FDA also awarded a Commissioner’s National Priority Voucher for zongertinib, underscoring its potential to meet critical patient needs for this rare and aggressive cancer.

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About HER2 (ERBB2)-mutant 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.² The condition is often diagnosed at a late stage, and fewer than 1 in 10 patients are alive five years after diagnosis.^6,7 People living with advanced NSCLC can experience a detrimental physical, psychological, and emotional impact on their daily lives.^8,9,10 There remains a high unmet need for additional treatment options for people living with advanced NSCLC.

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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.²

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About HERNEXEOS^® (zongertinib tablets)
HERNEXEOS (zongertinib tablets) is an irreversible tyrosine kinase inhibitor (TKI) that inhibits HER2 (ERBB2).^1,11 HERNEXEOS has been approved by the U.S. Food and Drug Administration (FDA) as the first orally administered, targeted therapy for adult patients with HER2 (ERBB2)-mutant advanced non-small cell lung cancer.

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Comprehensive biomarker testing using next generation sequencing determines a patient’s eligibility for treatment with HERNEXEOS by identifying HER2 (ERBB2)-mutant advanced NSCLC.^1,4

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The treatment is being evaluated in ongoing trials, across a range of earlier stages and advanced solid tumors with HER2 alterations. Beamion LUNG-2 is an ongoing Phase III controlled study evaluating zongertinib as a first-line treatment for patients with advanced NSCLC that has HER2 tyrosine kinase domain mutations (NCT06151574). Beamion LUNG-3 is a Phase III clinical trial investigating zongertinib as an adjuvant monotherapy in patients with early-stage, resectable NSCLC (Stage II-IIIB) with HER2 (ERBB2)-mutations (NCT07195695). 

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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 Boehringer-Ingelheim.com and Boehringer-Ingelheim.com/US.

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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 Boehringer-Ingelheim.com and Boehringer-Ingelheim.com/US.

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The following information is intended for U.S. audiences only:

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About HERNEXEOS^®
HERNEXEOS^® (zongertinib tablets) is a kinase inhibitor indicated for the treatment of adult patients with unresectable or metastatic non-squamous non-small cell lung cancer (NSCLC) whose tumors have HER2 (ERBB2) tyrosine kinase domain activating mutations, as detected by an FDA-authorized test.

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This indication is approved under accelerated approval based on objective response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

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Boehringer Ingelheim’s CareConnect4Me patient support program
Boehringer’s goal is to make HERNEXEOS^® (zongertinib tablets) easily accessible in the U.S. through a comprehensive patient support program, CareConnect4Me^TM, that provides a broad range of access and clinical support solutions, including financial support services. For those in the U.S., visit www.HERNEXEOS.com or call 1-855-297-5903 to learn more.

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What is HERNEXEOS (zongertinib tablets)?
HERNEXEOS is a prescription medicine used to treat adults with a type of lung cancer called non–squamous non–small cell lung cancer (NSCLC) that:

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Your healthcare provider will perform a test to make sure HERNEXEOS is right for you.

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It is not known if HERNEXEOS is safe and effective in children.

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IMPORTANT SAFETY INFORMATION

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Before taking HERNEXEOS, tell your healthcare provider about all of your medical conditions, including if you:

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Females who are able to become pregnant:

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Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. HERNEXEOS may affect the way other medicines work, and other medicines may affect how HERNEXEOS works.

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Know the medicines you take. Keep a list of them to show your healthcare provider or pharmacist when you get a new medicine.

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What are the possible side effects of HERNEXEOS?
HERNEXEOS may cause serious side effects, including:

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Your healthcare provider may temporarily stop, decrease your dose, or permanently stop treatment with HERNEXEOS if you have serious side effects.

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The most common side effects of HERNEXEOS include:

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The most common severe abnormal blood tests include decreased white blood cell count, increased liver function tests, and decreased potassium levels.

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HERNEXEOS may cause fertility problems in females and males, which may affect your ability to have children. Talk to your healthcare provider if this is a concern for you.

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These are not all of the possible side effects of HERNEXEOS. Call your doctor for medical advice about side effects. For more information, ask your healthcare provider or pharmacist.

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You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088.

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CL-HER-100001 02.2026

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 MPR-US-104010

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¹ HERNEXEOS Prescribing Information.  
² Baraibar I, et al. Novel drugs targeting EGFR and HER2 exon 20 mutations in metastatic NSCLC. Crit Rev Oncol Hematol. 2020;148:102906.
³ Li, B.T. et al. Trastuzumab Deruxtecan in HER2-Mutant Non–Small-Cell Lung Cancer. N Engl J Med. 2022;386:241–51.
⁴ Zeng J, Ma W, Young RB, Li T. Targeting HER2 genomic alterations in non-small cell lung cancer. J Natl Cancer Cent. 2021;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: November 2025).
⁶ Casal-Mouriño, A. et al. Epidemiology of stage III lung cancer: frequency, diagnostic characteristics, and survival. Transl Lung Cancer Res. 2021;10(1):506-518
⁷ National Cancer Institute. Surveillance, Epidemiology, and End Results (SEER). 5-Year Survival Rates. Available at: https://www.seer.cancer.gov/csr/1975_2016/results_merged/topic_survival.pdf (Accessed: November 2025).
⁸ Valentine, T. R. et al. Illness Perceptions and Psychological and Physical Symptoms in Newly Diagnosed Lung Cancer. Health Psychol. 2022;41(6): 379–388.
⁹ 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;145:195-204.
¹⁰ Presley, C. J. et al. Functional Disability Among Older Versus Younger Adults With Advanced Non–Small-Cell Lung Cancer. JCO  Oncol Pract. 2021;17(6):e848–e858.
¹¹ Wilding B, Woelflingseder L, Baum A, et al. Zongertinib (BI 1810631), an Irreversible HER2 TKI, Spares EGFR Signaling and Improves Therapeutic Response in Preclinical Models and Patients with HER2-Driven Cancers. Cancer Discov. 2025;15(1):119-138. doi:10.1158/2159-8290.CD-24-0306

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