On October 17, 2025 Boehringer Ingelheim reported positive results from the Beamion LUNG-1 trial evaluating HERNEXEOS (zongertinib tablets) 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). HERNEXEOS demonstrated efficacy with a confirmed objective response rate (ORR) of 77%. The data were featured at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2025.

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"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 (Free ESMO Whitepaper) demonstrated a manageable safety profile for HERNEXEOS 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.

HERNEXEOS 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 HERNEXEOS as a first-line therapy 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 HERNEXEOS 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 HERNEXEOS (zongertinib tablets)
HERNEXEOS (zongertinib tablets) is an irreversible tyrosine kinase inhibitor (TKI) that selectively inhibits HER2 (ERBB2). HERNEXEOS was recently approved by the U.S. Food and Drug Administration (FDA) as the first orally administered, targeted therapy 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 these indications may be contingent upon verification and description of clinical benefit in a confirmatory trial.

The U.S. FDA also granted Breakthrough Therapy Designation for HERNEXEOS for use in a first-line setting.

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.

(Press release, Boehringer Ingelheim, OCT 17, 2025, View Source [SID1234656751])