Updated data from Beamion LUNG-1 study on zongertinib shows encouraging efficacy in previously treated HER2 mutated lung cancer patients

• Zongertinib (120 mg QD) once a day (n=75) achieved a confirmed ORR of 71% by central review with a disease control rate of 93%
• Initial time-to-event data suggest that responses with zongertinib are durable, 6-month progression-free survival (PFS) and duration of response (DoR) rates were 69% and 73%, respectively. At data cut-off, 55% of patients remained on treatment
• Data from Cohort 1 are still maturing, the median PFS as well as median DoR will be reported at an upcoming conference

"This data update adds to the body of evidence indicating that zongertinib could be a future option for patients with non-small cell lung cancer who have activating HER2 mutations, a patient population for which targeted treatment options are currently severely limited," said the presenting investigator, Dr. Noboru Yamamoto, MD., PhD., at the National Cancer Center Hospital’s, Department of Experimental Therapeutics, Japan. “These data demonstrate the potential of zongertinib and support the long-term vision to change the benchmark for HER2 mutation driven cancers.”

Why it matters

• According to the World Health Organization, 2.21 million people were diagnosed with lung cancer in 2020, making it the second most common cancer worldwide. NSCLC accounts for the majority of cases (80-85%). ¹ Among these, 2 to 4% have HER2 mutations ^2,3; these patients may respond poorly to the current standards of care, including chemotherapy and immunotherapy. Therefore, a high unmet need for additional treatment options remains.⁴
• The condition is diagnosed at a late stage in 80% of cases, with fewer than 3 in 10 patients alive five years after diagnosis.^5,6  People living with advanced NSCLC can experience a detrimental physical, psychological, and emotional impact on their daily lives. 
• Boehringer Ingelheim is deeply committed to the field of oncology. Our ambition is to deliver life-changing, best-in-class treatments for the most hard-to-treat cancers. 

About non-small cell lung cancer (NSCLC) 

Lung cancer claims more lives than any other cancer type and the incidence is set to increase to over 3 million cases worldwide by 2040.⁷  NSCLC is the most common type of lung cancer.⁴ The condition is often diagnosed at a late stage,⁵  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. 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).²  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. ⁸

About zongertinib 

Zongertinib (also known as BI 1810631) is an investigational oral HER2-specific tyrosine kinase inhibitor (TKI) that is being developed as a potential treatment for HER2 mutated non-small cell lung cancer (NSCLC). Zongertinib was granted FDA Fast Track Designation in 2023, then in 2024 it was granted Breakthrough Therapy Designation by the U.S. FDA and China CDE for the treatment of adult patients with advanced, unresectable or metastatic NSCLC whose tumors have activating HER2 mutations and who have received prior systemic therapy.

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 unresectable or metastatic solid tumors with HER2 alterations. The study has 2 parts. The first part is open to adults with different types of advanced cancer with HER2 alterations that include mutations, amplifications, over-expression and fusions for whom previous treatment was not successful. The second part is open to people with HER2-mutant non-small cell lung cancer. Beamion LUNG-2 is a phase 3, open label, randomized, active-controlled study that will enroll 270 patients with unresectable, or metastatic non-squamous NSCLC harboring HER2 tyrosine kinase domain mutations to evaluate zongertinib compared with standard of care. 

About Boehringer Ingelheim in Oncology 

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.

About Boehringer Ingelheim

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 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. More than 53,500 employees serve over 130 markets to build a healthier, more sustainable, and equitable tomorrow.  

Zongertinib is an investigational molecule and has not been approved for use by any regulatory authority. The efficacy and safety have not yet been established.

References

¹ Molina JR, Yang P, Cassivi SD, Schild SE, Adjei AA. Non-small cell lung cancer: epidemiology, risk factors, treatment, and survivorship. Mayo Clin Proc. 2008 May;83(5):584-94.

² Ruiter G. et al. Phase Ib Analysis of Beamion LUNG-1: Zongertinib (BI 1810631) in Patients with HER2-Mutant NSCLC. presented at WCLC, San Diego, 7-10 September, 2024.

³ 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).

⁴ Zappa C & Mousa Non-small cell lung cancer: current treatment and future advances, Transl Lung Cancer Res. 2016 Jun; 5(3): 288–300.

⁵ Polanco D et al. Prognostic value of symptoms at lung cancer diagnosis: a three-year observational study. J Thorac Dis 2021;13:1485–1494

⁶ National Cancer Institute Surveillance, Epidemiology, and End Results (SEER). https://seer.cancer.gov/statfacts/html/lungb.html (Accessed: December 2024).

⁷ 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: December 2024).

⁸ Galogre M, et al. A review of HER2 overexpression and somatic mutations in cancers, Critical Reviews in Oncology/Hematology, Volume 186, 2023, 103997