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 percent. 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. A response rate of 77 percent 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,” said the presenting author, Professor 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.

Of the responders (77 percent), eight percent of patients achieved complete response, 69 percent achieved partial response and 96 percent 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 percent of patients remaining on treatment and encouraging six-month rates for DoR of 80 percent and PFS of 79 percent. 

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 (AEs) led to dose reductions in 11 patients (15 percent) and dose discontinuations in seven patients (nine percent). The most commonly reported AEs were grade-I diarrhoea and rash.

Zongertinib was recently granted Breakthrough Therapy Designation (BTD) by the US 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 tumours have HER2 TKD activating mutations.

Beamion LUNG-2 (NCT06151574), a phase-III randomised study evaluating Zongertinib as the 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 Zongertinib for treatment-naïve patients with advanced Non-Small Cell Lung Cancer with activating HER2 mutations. Employing our dual approach to oncology, we are advancing both cancer cell and immune cell-directed therapies to pioneer breakthroughs for patients,” said Shashank Deshpande, Chairman of the Board of Managing Directors and Head of Human Pharma at Boehringer Ingelheim.

HER2 (ERBB2)-mutant NSCLC is a disease characterised by its aggressive nature and poor prognosis. Up to four percent of lung cancers are driven by HER2 (ERBB2) mutations (or gene alterations). 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 tumour growth and spread. 

Lung cancer claims more lives than any other cancer type and the incidence is set to increase to over three million cases worldwide by 2040. NSCLC is the most common type of lung cancer. The condition is often diagnosed at a late stage, and fewer than three in 10 patients are alive five years after diagnosis. People living with advanced NSCLC can experience a detrimental, physical, psychological, and emotional impact on their daily lives. There remains a high unmet need for additional treatment options for people living with advanced NSCLC. Up to four percent of lung cancers are driven by HER2 (ERBB2) mutations (or gene alterations). 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 tumour growth and spread.

Zongertinib is an irreversible Tyrosine Kinase Inhibitor (TKI) that selectively inhibits HER2 (ERBB2) while sparing wild-type EGFR, thereby minimising associated toxicities.

Zongertinib has been approved by the US FDA as the first orally administered, targeted therapy for previously treated patients with HER2 (ERBB2)-mutant advanced NSCLC. The US FDA also granted BTD 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 tumours have activating HER2 (ERBB2) mutations and who have received at least one line of prior systemic therapy. China’s CDE also granted BTD 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 it the first oral molecularly targeted therapy available in Japan for previously treated, unresectable, advanced, or recurrent HER2 (ERBB2)-mutant NSCLC.

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 tumours 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 tumours 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, randomised, active-controlled study in patients with unresectable, locally advanced or metastatic non-squamous NSCLC harbouring 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, randomised, controlled, multi-centre 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.