The U.S. Food and Drug Administration (FDA) has approved zongertinib (Hernexeos®; Boehringer Ingelheim), a tyrosine kinase inhibitor (TKI) that selectively inhibits HER2 (ERBB2)[1]
Simultaneously with the approval of zongertinib the FDA approved Thermo Fisher’s Oncomine Dx Target Test, a next-generation sequencing (NGS-) based companion diagnostic (CDx) to advance personalization of lung cancer treatment. The test is especially designed to identify patients eligible for the treatment withe zongertinib.
Zongertinib is an orally administered drug indicated for the treatment of adult patients diagnosed with unresectable, advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) whose tumors have human epidermal growth factor receptor 2 (HER2; ERBB2) tyrosine kinase domain activating mutations, as detected by an FDA-approved test, and who have received prior systemic therapy.[1]
Next-generation sequencing is an increasingly important tool in the development of companion diagnostics, and “these approvals mark a significant advancement in the personalization of lung cancer treatment, says GlobalData, a leading data and analytics company,” noted Alexandra Murdoch, Senior Medical Analyst at GlobalData, an analytics company.
Claiming more lives
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.[2][3] NSCLC is the most common type of lung cancer. [4] Due to a lack of symptoms and misdiagnoses, [5] most patients with NSCLC present at stage III or IV, where the disease has metastasized locally or to other organs.[6] The estimated 5-year survival rate historically has been less than 10% for metastatic disease. [7][8][9] People living with advanced NSCLC can experience a detrimental physical, psychological, and emotional impact on their daily lives.[10][11][12]
The novel treatment was approved under the FDA’s Accelerated Approval Program, based on objective response rate and duration of response, after securing Priority Review as well as Breakthrough Therapy and Fast Track Designations.[1] Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. [1] In addition, treatment with zongertinib is being evaluated in additional ongoing trials, across a range of advanced solid tumors with HER2 alterations.
“With the approval of zongertinib, we have an effective, targeted, orally administered treatment option for patients with HER2 (ERBB2)-mutant non-small cell lung cancer in the U.S. that not only elicits a durable response but, importantly, has a manageable safety profile,” explained John Heymach, MD, PhD, chair of Thoracic/Head and Neck Medical Oncology at The University of Texas MD Anderson Cancer Center, and coordinating investigator for the Beamion-LUNG 1 trial (NCT04886804)
“In a patient population where there are currently limited treatment options, this approval represents a significant advancement in cancer care,” Heymach added.
Beamion-LUNG 1 trial
Accelerated approval is based on data from the Phase Ib Beamion-LUNG 1 trial, demonstrating an objective response rate of 75% (N=71), 6% of patients had a complete response and 69% of patients had a partial response and a duration of response of ≥6 months in 58% of patients (n=53).[1][2]
The Oncomine Dx Target Test is now validated to detect HER2-TKD activating mutations in NSCLC and serves as a critical tool to identify patients who are candidates for zongetinib treatment. The CDx proves to be an essential part of the treatment.
Positive results from the Beamion-LUNG 1 trial were previously presented at the 2025 annual meeting of the American Association for Cancer Research (AACR) and simultaneously published in The New England Journal of Medicine.[2]
The study results showed that zongertinib demonstrated a manageable safety profile with a 2.9% discontinuation rate. In the pooled safety population, the most common (> 20%) adverse reactions were diarrhea (53%), hepatotoxicity (27%), rash (27%), fatigue (22%), and nausea (21%).[1][2]
“We are grateful to be able to bring forward zongertinib, which has the potential to reset the benchmark for those living with HER2-mutant advanced non-small cell lung cancer, a condition associated with a particularly poor prognosis,” said Shashank Deshpande, Chairman of the Board of Managing Directors and Head of Human Pharma at Boehringer Ingelheim.
“Believing in the power of scientific innovation, we aim to provide meaningful improvements to this patient population. Recognizing its potential, we accelerated development to deliver this new treatment option to patients within four years of starting the first clinical trial,” Deshpande added.
NGS-based test
“Thermo Fisher’s Oncomine Dx Target Test has been a pioneer in NGS-based CDx platforms, with the first approval for screening for multiple NSCLC therapies in 2017. The current addition of HER2-TKD mutation detection further broadens the panel’s utility in targeted therapy selection,” said GlobalData’s Murdoch.
By evaluating multiple actionable biomarkers in a single test, NGS-based CDx eliminates the delays of sequential assays, which is crucial in fast-progressing cancers like NSCLC. Thermo Fisher’s ongoing partnerships with pharmaceutical companies streamline the co-development and simultaneous approval of drugs and their CDx, enhancing treatment rollout efficiency.
Thermo Fisher’s Oncomine Dx Target Test is not the only CDx on the market, but a vast majority of the approved CDx are for oncology. A recent GlobalData report, Companion Diagnostics, shows that both pipeline and marketed CDx products have cancer as the top indication. Furthermore, GlobalData expects the oncology diagnostics market to grow significantly, from $1.9 billion in 2022 to over $3.1 billion in 2030.
Comprehensive biomarker testing using next generation sequencing determines a patient’s eligibility for treatment with zongertinib by identifying HER2 (ERBB2)-mutant advanced NSCLC.[1][2]
“CDx are a crucial part of treatment for many patients. The ability to determine eligibility for targeted therapies, especially in oncology, can improve treatment significantly,” explained.
“By pairing a highly targeted HER2-TKD therapy with a NGS-based CDx, healthcare professionals can more rapidly and accurately identify eligible patients, helping to deliver effective treatment. As technologies like the Oncomine platform continue to evolve, the integration of precision testing with innovative therapies promises to bring the benefits of precision medicine to more patients,” she added.
Targeting HER2 mutations in lung cancer
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][4][14] 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]
“The advocacy community is thrilled about the approval of zongertinib, as it is another testament to the importance of personalized options for lung cancer that allow for a much more targeted approach for a subgroup of patients who have been waiting many years for innovative treatments,” said Marcia Horn, President and CEO, International Cancer Advocacy Network and Executive Director of the Exon 20 Group/HER2 Warriors.
“Understanding your cancer’s unique biomarkers, including HER2, through comprehensive testing is critical for all patients with NSCLC, as it can unlock targeted treatment options,” Horn concluded.
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Clinical trials
Beamion LUNG-1: A Study to Test Different Doses of Zongertinib in People With Different Types of Advanced Cancer (Solid Tumours With Changes in the HER2 Gene) – ClinicalTrials.gov ID NCT04886804
Beamion LUNG-2: A Study to Test Whether Zongertinib (BI 1810631) Helps People With Advanced Non-small Cell Lung Cancer With HER2 Mutations Compared With Standard Treatment – ClinicalTrials.gov ID NCT06151574
Highlights of Prescribing Information
Zongertinib (Hernexeos®; Boehringer Ingelheim){Prescribing Information}
References
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Featured image: Lung radiography | Doctor examining a lung. Photo courtesy: © 2016 – 2025 Fotolia/Adobe. Used with permission
DOI
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