Boehringer's new zongertinib data demonstrate durable and clinically meaningful results in patients with HER2 (ERBB2)-mutant advanced NSCLC

Hamilton Spectator

28-04-2025

Ingelheim, Germany / Ridgefield, Conn., U.S., April 28, 2025
Boehringer Ingelheim reported new and updated data from the Beamion LUNG-1 trial evaluating zongertinib in previously treated patients with
HER2
(ERBB2)-mutant advanced non-small cell lung cancer (NSCLC). The data were featured in the official
press program
at the American Association for Cancer Research (AACR) Annual Meeting 2025 and simultaneously published in
The New England Journal of Medicine
.
'These data presented at AACR 2025 suggest that zongertinib may offer a new approach to treating patients with non-small cell lung cancer with activating
HER2
mutations,' said the trial's coordinating investigator, Dr. John Heymach, MD, PhD, chair of Thoracic/Head and Neck Medical Oncology at The University of Texas MD Anderson Cancer Center. 'Notably, more than 70% of patients experienced a tumor response, which is highly meaningful for those with this subtype of lung cancer. If approved by the FDA, zongertinib would be the first oral, targeted treatment option that addresses an unmet need for these patients.'
Data from the most recent analysis showed durable response and clinically meaningful results with zongertinib in previously treated patients with advanced NSCLC who have
HER2
mutations within the tyrosine kinase domain (TKD) (N=75). The ORR was 71% (95% CI: 60-80), with 7% complete response, 64% partial response, and 96% disease control in previously treated patients. Additionally, zongertinib had intracranial activity in previously treated patients (n=27, who were evaluable) with brain metastases, with 41% achieving response and 81% disease control. At AACR 2025, the median DoR of 14.1 and median PFS of 12.4 months were presented for the first time.
Itziar Canamasas, Global Head of Oncology at Boehringer Ingelheim, said: 'Zongertinib has the potential to reset the benchmark for patients with
HER2
-mutant advanced non-small cell lung cancer, a patient population that has historically faced a poor prognosis. At Boehringer, we take cancer care personally; these updated data reaffirm our approach of addressing areas with high unmet need and letting our research guide us to where we can have the biggest impact for patients.'
Initial results in patients with advanced NSCLC with
HER2
mutations in the TKD, who were previously treated with both platinum-based chemotherapy and subsequent HER2-directed antibody drug conjugates (ADC) (N=31), demonstrated an ORR of 48% (95% CI: 32-65) with 97% (95% CI: 15-52) of patients achieving disease control. An exploratory cohort (n=20) that included previously treated patients with advanced NSCLC with
HER2
mutations outside of the TKD demonstrated an investigator-assessed ORR of 30% (95% CI: 15-52) and a DCR of 65% (95% CI: 43-82). This is the largest known dataset of patients with previously treated advanced NSCLC
who have
HER2
mutations outside the TKD. Both of these data sets were presented at AACR 2025 and are included in
The New England Journal of Medicine
publication.
The data presented at AACR 2025 demonstrated a manageable safety profile for zongertinib with no drug-related deaths, cases of interstitial lung disease (ILD) or cardiotoxicity reported. The most commonly reported adverse event (AE) was grade 1 diarrhea, with low incidence of grade ≥3 drug-related events (17%) in patients with TKD mutations (N=75).
ORR, %
95% CI
71*
60-80
48*
32–65
30**
15-52
DCR, %
95% CI
96*
89-99
97*
84-99
65**
43-82
Median DoR
95% CI
14.1 months***
6.9–NE
Median PFS
95% CI
12.4 months***
8.2–NE
*Confirmed response by BICR according to RECIST v1.1
**Confirmed response by investigator review according to RECIST v1.1
*** Median DoR and median PFS are based on Kaplan Meier estimates
Lung cancer claims more lives than any other cancer type1 and the incidence is set to increase to over 3 million cases worldwide by 2040.2 NSCLC is the most common type of lung cancer.3 The condition is often diagnosed at a late stage,4 and fewer than 3 in 10 patients are alive five years after diagnosis.5 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 4% of lung cancers are driven by
HER2
mutations (or gene alterations).6 Mutations in
HER2
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.7
Zongertinib is an investigational irreversible tyrosine kinase inhibitor (TKI) that selectively inhibits
HER2
while sparing wild-type EGFR, thereby limiting associated toxicities. This orally administered, targeted therapy was granted FDA Fast Track Designation in 2023, followed by Breakthrough Therapy Designation in the U.S. and China for the treatment of adult patients with unresectable or metastatic NSCLC whose tumors have activating
HER2
mutations and who have received prior systemic therapy. An application for accelerated approval was granted Priority Review status by the FDA in February 2025. In addition, Japan's Pharmaceuticals and Medical Devices Agency granted Orphan Drug Designation to zongertinib.
A recent study has shown pre-clinically that the investigational compound zongertinib has potential for further clinical study in HER2 dependent solid cancers as monotherapy and as concurrent treatment with ADC therapy. In addition, zongertinib is being evaluated in Beamion LUNG-2 (
NCT06151574
), a global Phase III trial, compared to standard of care as first-line treatment in patients with unresectable, locally advanced or metastatic NSCLC who have activating
HER2
TKD mutations.
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
alterations. The study has 2 parts. The first part is open to adults with different types of advanced cancer (solid tumors with changes in the
HER2
gene) for whom previous treatment was not successful. The second part is open to people with advanced non-small cell lung cancer with a specific mutation in the
HER2
gene. Beamion LUNG-2 is a phase 3, open label, randomized, active-controlled study in patients with unresectable, locally advanced or metastatic non-squamous NSCLC harboring
HER2
TKD mutations to evaluate zongertinib compared with standard of care.
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.
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
www.boehringer-ingelheim.com
.
References
1 World Health Organization Cancer Factsheet.
https://www.who.int/news-room/fact-sheets/detail/cancer
(Accessed April 2025).
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 August 2024).
3 Zappa C & Mousa Non-small cell lung cancer: current treatment and future advances, Transl Lung Cancer Res. 2016 Jun; 5(3): 288–300.
4 Polanco D et al. Prognostic value of symptoms at lung cancer diagnosis: a three-year observational study. J Thorac Dis 2021;13:1485–1494
5 National Cancer Institute Surveillance, Epidemiology, and End Results (SEER).
https://seer.cancer.gov/statfacts/html/lungb.html
(Accessed: August 2024).
6 Arcila, M. E. et al. Prevalence, clinicopathologic associations, and molecular spectrum of ERBB2 (HER2) tyrosine kinase mutations in lung adenocarcinomas. Clin. cancer Res. an Off. J. Am. Assoc. Cancer Res. 18, 4910–4918 (2012).
7 Galogre M, et al. A review of HER2 overexpression and somatic mutations in cancers, Critical Reviews in Oncology/Hematology, Volume 186, 2023, 103997.