Zongertinib

What it is and how it works

Mechanism of Action 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. In vivo, zongertinib demonstrated anti-tumor activity in mouse xenograft models of NSCLC harboring HER2 tyrosine kinase domain activating mutations.

Mechanism class: HER2/Neu/cerbB2 Antagonists · Breast Cancer Resistance Protein Inhibitors

Indications

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 . This indication is approved under accelerated approval based on objective response rate and duration of response . Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. HERNEXEOS is a kinase inhibitor 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. This indication is approved under accelerated approval based on objective response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

Dosage and administration (summary)

Select patients for treatment with HERNEXEOS based on the presence of HER2 (ERBB2) tyrosine kinase domain activating mutations. 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. 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 or plasma specimens . If no mutation is detected in a plasma specimen, test tumor tissue.

Contraindications

None. None.

Warnings and precautions

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. Left Ventricular Dysfunction : Monitor LVEF at baseline prior to administration and at regular intervals during treatment and as clinically indicated.

Pregnancy

Pregnancy Risk Summary Based on findings from animal studies and its mechanism of action , 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.

Storage and supply

Storage and Handling Store at 20°C to 25°C (68°F to 77°F), excursions permitted to 15°C to 30°C (59°F to 86°F) . Store in the original container to protect from moisture. Keep the bottle tightly closed. Do not remove the desiccants. Once opened, use within 3 months. Discard any unused tablets 3 months after opening the bottle.

Source: Zongertinib (Hernexeos) — US FDA prescribing information, 2026-08-13, DailyMed. Summarised and shortened; the full label governs. Iranian registration, indications and labelling may differ.