NSCLC Update: Oral HER2 TKI Approval

     On August 8^th 2025, the FDA announced accelerated approval for a new small molecule aimed at treating unresectable or metastatic non-squamous Non-small cell lung cancer (NSCLC) with HER2 (ERBB2) tyrosine kinase domain (TKD) activating mutations. Breakthrough designation was awarded after reaching the primary and secondary safety and efficacy endpoints. Supporting data was reported in New England Medical Journal in April 2025.

Drug Info:

• Name(s): zongertinib, BI 1810631, Hernexeos

• Class: small molecule (non-biologic)

• Route of Administration: oral tablet

• Mechanism of Action: Tyrosine Kinase Inhibitor (TKI)

  • Target: Human epidermal growth factor 2 (HER2, ERBB2)

Patient Population:

• Disease: Non-squamous NSCLC

  • Stage: Unresectable or metastatic (III or IV)

  • Characteristics: HER2 TKD aberration, confirmed by FDA approved tumor testing

• Treatment History: Received any prior systemic therapy

Study Info:

• Identifying:

  • Short Name: Beamion LUNG-1

  • NCT: NCT04886804

  • Sponsor: Boehringer Ingelheim (Germany)

  • Long Name: A Study to Test Different Doses of Zongertinib in People With Different Types of Advanced Cancer (Solid Tumours With Changes in the HER2 Gene)

• General:

  • Phase: Ia-Ib

  • Drug: zongertinib monotherapy

  • Endpoints:

    • Primary: Safety (dose, toxicity); Efficacy (ORR)

    • Secondary: Safety (pharmacokinetics, toxicity); Efficacy (DoR, DC, PFS, OS)

  • Location: International (US, Europe, Australia, Asia)

• Patient Population:

  • Phase Ia: “Basket Study” – any confirmed malignancy with HER2 aberration or exhausted available treatment options

  • Phase Ib: NSCLC, multiple cohorts with or without prior platinum-based chemotherapy, with or without prior HER2-directed ADC, with or without HER2 TKD mutation

  • Inclusion/Exclusion: Standard, leaning generous

• Other:

  • Beamion LUNG-2 (NCT06151574): Ongoing Phase III with zongertinib in NSCLC

If you would like to know more about this study, the results, or the breakthrough designation drug approval process, speak with our experts in CT101!

C3 does not endorse any specific treatment or drug. C3 does not have affiliations with any pharmaceutical or biotechnology company.