On 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) (Press release, Boehringer Ingelheim, APR 28, 2025, View Source [SID1234652268]). The data was featured in the official press program at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2025 and simultaneously published in The New England Journal of Medicine.
Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
"These data presented at AACR (Free AACR Whitepaper) 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 (Free AACR Whitepaper) 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."
Additional analyses of previously treated patients with HER2 mutations demonstrated zongertinib’s clinically meaningful results
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 (Free AACR Whitepaper) 2025 and are included in The New England Journal of Medicine publication.
The data presented at AACR (Free AACR Whitepaper) 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).
AACR 2025 presentation: summary of key efficacy endpoints
Endpoint
Patients with TKD mutations (N = 75)
Patients with TKD mutations and
prior HER2-directed ADC treatment (N = 31)
Patients with non-TKD mutations (n = 20)
ORR, %
95% CI
71*
60-80
48*
32–65
30**
15-52
CR, %
7*
3*
0**
PR, %
64*
45*
30**
DCR, %
95% CI
96*
89-99
97*
84-99
65**
43-82
Median DoR
95% CI
14.1 months***
6.9–NE
n/a
n/a
Median PFS
95% CI
12.4 months***
8.2–NE
n/a
n/a
*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
About non-small cell lung cancer (NSCLC)
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
About zongertinib
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)4, 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.
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 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.