FDA grants HERNEXEOS® Breakthrough Therapy Designation for first line use in HER2 (ERBB2)-mutant advanced NSCLC

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Sep 03, 2025, 10:51 ET

Breakthrough Therapy Designation is based on results from the Beamion-LUNG 1 clinical trial evaluating HERNEXEOS^® (zongertinib tablets) as a first-line treatment in HER2 (ERBB2)-mutant advanced NSCLC
Follows recent accelerated approval of HERNEXEOS for previously treated patients with HER2 (ERBB2)-mutant advanced NSCLC from the U.S. Food and Drug Administration

RIDGEFIELD, Conn., Sept. 3, 2025 /PRNewswire/ -- Boehringer Ingelheim today announced HERNEXEOS^® (zongertinib tablets) has been granted Breakthrough Therapy Designation by the U.S. Food and Drug Administration (FDA) for first-line 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.

"Exploring accelerated review pathways is part of Boehringer's strategy to have an unprecedented and generational impact on people facing cancer. We are incredibly pleased that HERNEXEOS has received Breakthrough Therapy Designation for first-line use in patients living with HER2-mutant non-small cell lung cancer," said Vicky Brown, Senior Vice President and Head of Immunology, Oncology, and Eye Health, Boehringer Ingelheim. "This pathway was designed to expedite the development and review of promising medicines for serious diseases, and clearly highlights the potential of HERNEXEOS."

Breakthrough Therapy Designation is given to expedite the development and review of medicines for serious conditions where preliminary clinical evidence indicates that the medicine may demonstrate substantial improvement over currently available therapies.

HERNEXEOS was recently approved by the U.S. FDA for adult patients with unresectable or metastatic non-squamous NSCLC whose tumors have HER2 (ERBB2) tyrosine kinase domain (TKD) activating mutations, as detected by an FDA-approved test, and who have received prior systemic therapy. 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.

Boehringer will present new and updated HERNEXEOS data at the upcoming World Conference on Lung Cancer (WCLC) in September and European Society for Medical Oncology (ESMO) in October.

About HERNEXEOS^®HERNEXEOS is an irreversible tyrosine kinase inhibitor (TKI) that selectively inhibits HER2 while sparing wild-type EGFR, thereby limiting associated toxicities. Boehringer Ingelheim is investigating HERNEXEOS across a range of advanced solid tumors with HER2 alterations.

The therapy was conditionally approved for use as a monotherapy by China's National Medical Products Administration (NMPA) 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. It also recently received Breakthrough Therapy Designation from the Center for Drug Evaluation (CDE) of China's NMPA for the first line treatment of adult patients with unresectable or metastatic NSCLC harboring activating mutations in the HER2 TKD. This orally administered, targeted therapy has also been granted Orphan Drug Designation in Japan.

About non-small cell lung cancer (NSCLC)
Lung cancer claims more lives than any other cancer type and the incidence is set to increase to over 3 million cases worldwide by 2040.^1,2 NSCLC is the most common type of lung cancer.³ Due to a lack of symptoms and misdiagnoses,⁴ most patients with NSCLC present at stage III or IV, where the disease has metastasized locally or to other organs.⁵ The estimated 5-year survival rate historically has been less than 10% for metastatic disease.^6,7,8 People living with advanced NSCLC can experience a detrimental physical, psychological, and emotional impact on their daily lives.^9,10,11

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 unresectable or metastatic solid tumors with HER2 alterations. The study has 2 parts. The first part is open to adults with different types of advanced cancer with HER2 alterations that include mutations, amplifications, over-expression and fusions for whom previous treatment was not successful. The second part is open to people with HER2-mutant non-small cell lung cancer.

Beamion LUNG-2 is a Phase III, open label, randomized, active-controlled study that will enroll 416 patients with unresectable, or metastatic non-squamous NSCLC harboring HER2 tyrosine kinase domain mutations to evaluate zongertinib compared with standard of care. 

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.

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.

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:

cannot be removed by surgery or that has spread to other parts of your body (metastatic), and
has a certain mutation in the human epidermal growth factor receptor 2 (HER2) gene, and
who have previously received treatment by mouth or injection (systemic therapy).

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

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

IMPORTANT SAFETY INFORMATION

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

have liver problems.
have heart problems.
have lung or breathing problems other than lung cancer.
are pregnant or plan to become pregnant. HERNEXEOS can harm your unborn baby.

Females who are able to become pregnant:

- Your healthcare provider will do a pregnancy test before you start treatment with HERNEXEOS.
- Use an effective form of birth control (contraception) during treatment with HERNEXEOS and for 2 weeks after your last dose.
- Talk to your healthcare provider about birth control methods that might be right for you during this time.
- Tell your healthcare provider right away if you become pregnant or think you are pregnant during treatment with HERNEXEOS.
are breastfeeding or plan to breastfeed. It is not known if HERNEXEOS passes into your breastmilk. Do not breastfeed during treatment and for 2 weeks after your last dose of HERNEXEOS.

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.

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

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

liver problems. Liver problems are common with HERNEXEOS and can be severe and life-threatening. Your healthcare provider will do blood tests to check your liver function before you start taking HERNEXEOS and during your treatment. Tell your healthcare provider right away if you develop any signs and symptoms of liver problems, including:
- yellowing of your skin or the white part of your eyes (jaundice)
- dark or brown (tea colored) urine
- pain on the upper right side of your stomach area (abdomen)
- bleeding or bruising more easily than normal
- feeling very tired
- loss of appetite
- nausea or vomiting

heart problems that may affect your heart's ability to pump blood. HERNEXEOS can cause heart problems. Your healthcare provider will do tests to check your heart function before you start taking HERNEXEOS and during treatment. Tell your healthcare provider right away if you have any new or worsening symptoms of heart problems, including:
- feeling like your heart is pounding or racing
- dizziness
- tiredness
- feeling lightheaded
- shortness of breath
- loss of consciousness
- coughing
- swelling of your legs, ankles, or feet

lung problems. HERNEXEOS can cause lung problems that are severe or life-threatening. Tell your healthcare provider right away if you have any new or worsening symptoms of lung problems, including trouble breathing, shortness of breath, cough, or fever.

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

The most common side effects of HERNEXEOS include:

diarrhea. HERNEXEOS can cause severe diarrhea. Tell your healthcare provider right away if you have diarrhea.
liver problems
rash
feeling tired
nausea

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

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.

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.

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.

CL--100065 07.28.2025

For U.S. Healthcare Professionals, please see full Prescribing Information.

MPR-US-103736

References:
¹Zeng 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.
² 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: January 2025).
³ Baraibar I, et al. Novel drugs targeting EGFR and HER2 exon 20 mutations in metastatic NSCLC. Crit Rev Oncol Hematol. 2020;148:102906.
⁴ American Cancer Society. Lung Cancer Early Detection, Diagnosis, and Staging. Available at: https://www.cancer.org/cancer/lung-cancer/detection-diagnosis-staging/signs-symptoms.html (Accessed: January 2025).
⁵Casal-Mouriño, A. et al. Epidemiology of stage III lung cancer: frequency, diagnostic characteristics, and survival. Transl Lung Cancer Res. 2021;10(1):506-518.
⁶ National Cancer Institute Surveillance, Epidemiology, and End Results (SEER). 5-Year Survival Rates. https://www.seer.cancer.gov/csr/1975_2016/results_merged/topic_survival.pdf (Accessed July 2025).
⁷ Belaroussi, Y. et al. Survival outcomes of patients with metastatic non-small cell lung cancer receiving chemotherapy or immunotherapy as first-line in a real-life setting. Sci Rep. 2023.13, 9584.
⁸ Simeone, J. C. et al. Treatment patterns and overall survival in metastatic non-small-cell lung cancer in a real-world US setting. Fut. Oncol. Lond. Engl. 2019. 15(30), 3491–3502.
⁹ 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.
¹⁰ 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.
¹¹ 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.