Zongertinib

Zongertinib is a kinase inhibitor of human epidermal growth factor receptor 2 (HER2). In vitro, zongertinib inhibited phosphorylation of HER2, downstream signaling of HER2 (phosphorylation of ERK), and proliferation of lung cancer cells harboring HER2 tyrosine kinase domain activating mutations.

• HERNEXEOS is indicated for the treatment of adult patients with unresectable or metastatic non-squamous non-small cell lung cancer (NSCLC) whose tumors have HER2 (ERBB2) tyrosine kinase domain activating mutations, as detected by an FDA-authorized test [see Dosage and Administration (2.1) ] . This indication is approved under accelerated approval based on objective response rate and duration of response [see Clinical Studies (14) ] .ICD-10: C34.90

• None. None.contraindicated

Select patients for treatment with HERNEXEOS based on the presence of HER2 (ERBB2) tyrosine kinase domain activating mutations. ( 2.1 ) The recommended dosage of HERNEXEOS is based on body weight: ( 2.2 ) Patients weighing less than 90 kg: 120 mg ( 2.2 ) Patients weighing 90 kg or greater: 180 mg ( 2.2 ) Take HERNEXEOS orally once daily with or without food until disease progression or unacceptable toxicity. ( 2.2 ) 2.1 Patient Selection Select patients for treatment of unresectable or metastatic NSCLC based on the presence of HER2 (ERBB2) tyrosine kinase domain activating mutations in tumor specimens [see Clinical Studies (14) ] . Information on FDA-authorized tests for HER2 (ERBB2) tyrosine kinase domain activating mutations is available at: http://www.fda.gov/CompanionDiagnostics. 2.2 Recommended Dosage and Administration The recommended dosage of HERNEXEOS is based on body weight: Patients weighing less than 90 kg: 120 mg Patients weighing 90 kg or greater: 180 mg Take HERNEXEOS orally once daily with or without food until disease progression or unacceptable toxicity. Swallow HERNEXEOS tablets whole with water. Do not split, crush, or chew tablets. Missed Dose If a dose is missed within 12 hours, take the dose. If a dose is missed by more than 12 hours, skip the missed dose and take the next scheduled dose. Vomited Dose If a dose is vomited, do not take an additional dose. Take the next dose at the regularly scheduled time. 2.3 Dosage Modifications for Adverse Reactions The recommended dose reductions for adverse reactions are presented in Table 1.

Hepatotoxicity : Monitor liver function tests including ALT, AST, and total bilirubin at baseline prior to administration, every 2 weeks during the first 12 weeks, and then monthly thereafter as clinically indicated, with more frequent testing in patients who develop transaminase elevations. Interrupt, reduce the dose, or permanently discontinue HERNEXEOS based on severity. ( 5.1 ) Left Ventricular Dysfunction : Monitor LVEF at baseline prior to administration and at regular intervals during treatment and as clinically indicated. Interrupt, reduce the dose, or permanently discontinue HERNEXEOS based on severity. ( 5.2 ) Interstitial Lung Disease/Pneumonitis : Monitor for new or worsening symptoms indicative of ILD/pneumonitis (e.g., dyspnea, cough, fever). Interrupt, reduce the dose, or permanently discontinue HERNEXEOS based on severity. ( 5.3 ) Embryo-Fetal Toxicity : Can cause fetal harm. Advise patients of the potential risk to a fetus and to use effective contraception. ( 5.4 ) 5.1 Hepatotoxicity HERNEXEOS can cause severe and life-threatening hepatotoxicity, including drug induced liver injury. In the pooled safety population [see Adverse Reactions (6.1) ], based on adverse reaction data, hepatotoxicity occurred in 27% of patients treated with HERNEXEOS. Grade 3 drug induced liver injury occurred in 1.4% and Grade 4 in 0.3% of patients treated with HERNEXEOS. Grade 3 hepatic failure occurred in 0.3% of patients treated with HERNEXEOS.

The following adverse reactions are discussed in greater detail in other sections of the labeling: Hepatotoxicity [see Warnings and Precautions (5.1) ] Left Ventricular Dysfunction [see Warnings and Precautions (5.2) ] Interstitial Lung Disease/Pneumonitis [see Warnings and Precautions (5.3) ] Most common adverse reactions (≥ 20%) are diarrhea, rash, hepatotoxicity, fatigue, nausea, musculoskeletal pain, and upper respiratory tract infection. ( 6.1 ) The most common (≥ 2%) Grade 3 or 4 laboratory abnormalities were decreased lymphocytes, increased alanine aminotransferase, increased aspartate aminotransferase, increased gamma glutamyl transferase, decreased potassium, and decreased neutrophils. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Boehringer Ingelheim Pharmaceuticals, Inc. at 1-800-542-6257 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. The pooled safety population described in WARNINGS AND PRECAUTIONS reflects exposure to HERNEXEOS in 292 patients with unresectable or metastatic non-squamous NSCLC with HER2 (ERBB2) mutations who received HERNEXEOS as a single agent at 120 mg orally once daily until disease progression or unacceptable toxicity in Beamion LUNG-1 [see Clinical Studies (14) ] .

Lactation : Advise not to breastfeed. ( 8.2 ) 8.1 Pregnancy Risk Summary Based on findings from animal studies and its mechanism of action [see Clinical Pharmacology (12.1) ], HERNEXEOS can cause fetal harm when administered to a pregnant woman. There are no available data on the use of HERNEXEOS in pregnant women to inform a drug-associated risk. Oral administration of zongertinib to pregnant rats during the period of organogenesis caused structural abnormalities and alterations to growth at maternal exposures ≥ 19 times the human exposure based on AUC at the recommended dose [see Data ] . Advise pregnant women and females of reproductive potential of the potential risk to a fetus. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Animal Data In an embryo-fetal development study, pregnant rats received oral doses of 10, 30, or 60 mg/kg/day of zongertinib during the period of organogenesis (gestation day 7 to 18). Zongertinib caused decreased fetal weights, delayed development of the urinary system, and kidney hydronephrosis at 60 mg/kg/day (approximately 19 times the human exposure based on AUC at the recommended dose).

Metabolism

Zongertinib pharmacokinetics were observed at steady state in patients with advanced or metastatic solid tumors with HER2 aberrations at the approved recommended dosage and are presented as geometric mean (CV%), unless otherwise specified. Zongertinib maximum concentration (C max,ss ) is 3.0 (37%) µmol/L and the total systemic exposure (AUC) is 34 (34%) µmol*h/L following HERNEXEOS 120 mg orally daily.

Overdose in one patient who ingested 600 mg of HERNEXEOS resulted in nausea and vomiting.

• Aug 8, 2025NDANDA219042Boehringer Ingelheim

1. 1Diarrhoea1726%
2. 2Malignant Neoplasm Progression1218%
3. 3Disease Progression57.7%
4. 4Decreased Appetite46.2%
5. 5Metastases To Central Nervous System46.2%
6. 6Rash46.2%
7. 7Death34.6%
8. 8Epistaxis34.6%
9. 9Hepatic Cytolysis34.6%
10. 10Pyrexia34.6%
11. 11Blood Creatinine Increased23.1%
12. 12Dry Mouth23.1%
13. 13Dysgeusia23.1%
14. 14Headache23.1%
15. 15Hepatitis23.1%

The 10 most recently updated of 16 ClinicalTrials.gov registrations naming Zongertinib as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• Beamion LUNG-1: A Study to Test Different Doses of Zongertinib in People With Different Types of Advanced Cancer (Solid Tumours With Changes in the HER2 Gene)
  Active not recruiting · Phase 1 · Interventional · 608 enrolled · Boehringer Ingelheim
  NCT04886804updated 2026-06-12
• Beamion 44: A Study to Test How Well Zongertinib is Tolerated by People With Advanced Non-small Cell Lung Cancer With HER2 Mutations When Given in Combination With Chemotherapy With or Without Pembrolizumab
  Recruiting · Phase 2 · Interventional · 60 enrolled · Boehringer Ingelheim
  NCT07486817updated 2026-06-12
• Beamion PANTUMOR-1: A Study to Test Whether Zongertinib Helps People With Advanced Cancers With HER2 Alterations
  Recruiting · Phase 2 · Interventional · 430 enrolled · Boehringer Ingelheim
  NCT06581432updated 2026-06-09
• Beamion LUNG-2: A Study to Test Whether Zongertinib (BI 1810631) Helps People With Advanced Non-small Cell Lung Cancer With HER2 Mutations Compared With Standard Treatment
  Active not recruiting · Phase 3 · Interventional · 428 enrolled · Boehringer Ingelheim
  NCT06151574updated 2026-06-02
• A Phase II Study of Zongertinib Plus Fulvestrant in Participants With HR-positive/HER2-negative Advanced Breast Cancer Harboring HER2 Mutations.
  Not yet recruiting · Phase 2 · Interventional · 25 enrolled · MedSIR
  NCT07619066updated 2026-06-01
• Beamion LUNG-3: Adjuvant Zongertinib vs Standard Treatment in People With Completely Resected Stage II-IIIB NSCLC Harboring Activating HER2 TKD Mutations
  Recruiting · Phase 3 · Interventional · 400 enrolled · Boehringer Ingelheim
  NCT07195695updated 2026-06-01
• Beamion BCGC-1: A Study to Find a Suitable Dose of Zongertinib Used Alone and in Combination With Other Treatments to Test Whether it Helps People With Different Types of HER2+ Cancer That Has Spread
  Recruiting · Phase 1 · Phase 2 · Interventional · 768 enrolled · Boehringer Ingelheim
  NCT06324357updated 2026-05-26
• A Study in Healthy Men to Test Whether Zongertinib Influences the Amount of 4 Other Medicines (Dabigatran, Rosuvastatin, Metformin, and Furosemide) in the Blood
  Completed · Phase 1 · Interventional · 32 enrolled · Boehringer Ingelheim
  NCT06504862updated 2026-01-09
• A Study in Healthy Men to Test Whether Zongertinib Affects How 3 Other Medicines (Midazolam, Omeprazole, and Repaglinide) Are Taken up and Processed by the Body
  Completed · Phase 1 · Interventional · 16 enrolled · Boehringer Ingelheim
  NCT06494761updated 2025-12-02
• A Study in Healthy Men to Test Whether Carbamazepine Influences the Amount of Zongertinib in the Blood
  Completed · Phase 1 · Interventional · 16 enrolled · Boehringer Ingelheim
  NCT06028464updated 2025-11-05

Frequently asked questions

How does Zongertinib work?

Zongertinib is a kinase inhibitor of human epidermal growth factor receptor 2 (HER2). In vitro, zongertinib inhibited phosphorylation of HER2, downstream signaling of HER2 (phosphorylation of ERK), and proliferation of lung cancer cells harboring HER2 tyrosine kinase domain activating mutations.

What is Zongertinib used for?

According to FDA labeling, Zongertinib carries indications including: HERNEXEOS is indicated for the treatment of adult patients with unresectable or metastatic non-squamous non-small cell lung cancer (NSCLC) whose tumors have HER2 (ERBB2) tyrosine kinase domain activating mutations, as detected by an FDA-authorized test [see Dosage and Administration (2.1) ] . This indication is approved under accelerated approval based on objective response rate and duration of response [see Clinical Studies (14) ] .. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Zongertinib?

Zongertinib is classified as Human epidermal growth factor receptor 2 (HER2) tyrosine kinase inhibitors, Kinase Inhibitor, Breast Cancer Resistance Protein Inhibitors, HER2/Neu/cerbB2 Antagonists, Receptor Tyrosine Kinase Inhibitors, Cellular Proliferation Alteration.

What are the brand names for Zongertinib?

Zongertinib is marketed under brand names including Hernexeos.

What are the contraindications for Zongertinib?

Zongertinib labeling lists contraindications including: None. None.. Always consult the full prescribing information and a clinician.