Zongertinib is a novel kinase inhibitor indicated for the treatment of adult patients with unresectable or metastatic non-squamous non-small cell lung cancer (NSCLC) harboring activating mutations in the tyrosine kinase domain of HER2 (ERBB2).

How to Use Zongertinib

Eligibility Screening for Patients

For Zongertinib use, the presence of activating mutations in the tyrosine kinase domain of HER2 (ERBB2) in the tumor must be confirmed by an FDA-approved test.

Patients must be adults with unresectable or metastatic non-squamous NSCLC who have received prior systemic therapy.

Administration Regimen

Dose Calculation: The dose is adjusted based on body weight. A daily dose of 120mg is recommended for patients with a body weight <90kg, and 180mg daily for those with a body weight ≥90kg.

Administration Method: Take orally once daily, with or without food. Swallow the tablet whole; do not break, crush, or chew it.

Treatment Course: Continue treatment until disease progression or the occurrence of intolerable toxicity.

Management of Missed Dose: If the missed dose is within ≤12 hours, take the missed dose as soon as possible; if more than 12 hours have passed, skip the missed dose and take the next dose as scheduled.

Management of Vomiting: If vomiting occurs after taking the drug, do not take an additional dose; take the next dose as scheduled.

Dose Adjustment of Zongertinib

Adjustment Based on Adverse Reactions

Hepatotoxicity: If Grade 3 ALT/AST elevation or Grade 4 ALT/AST elevation without bilirubin elevation occurs, interrupt treatment until liver enzymes return to ≤Grade 1, then resume treatment at a reduced dose. If Grade 4 bilirubin elevation or ALT/AST ≥3 times the upper limit of normal (ULN) accompanied by bilirubin ≥2 times ULN occurs, permanently discontinue treatment.

Left Ventricular Dysfunction: If LVEF (Left Ventricular Ejection Fraction) decreases to 40-50% with a 10-19% reduction from baseline, interrupt treatment; resume at the original dose if LVEF recovers within 4 weeks. If LVEF <40% or decreases by ≥20% from baseline, reduce the dose or permanently discontinue treatment.

Interstitial Lung Disease/Pneumonitis: For Grade 2 symptoms, suspend treatment until resolution, then resume at a reduced dose. For Grade 3 or 4 symptoms, permanently discontinue treatment.

Diarrhea: If Grade 2 diarrhea persists for ≥2 days or Grade 3 or above diarrhea occurs, interrupt treatment; resume at a reduced dose after resolution. If symptoms do not resolve to ≤Grade 1 within 14 days, permanently discontinue treatment.

Adjustment Due to Drug Interactions

Strong CYP3A Inducers: Concomitant use should be avoided. If unavoidable, increase the daily dose to 240mg for patients with a body weight <90kg and to 360mg for those with a body weight ≥90kg. Resume the original dose 7-14 days after discontinuing the inducer.

BCRP Substrate Drugs: Avoid concomitant use of BCRP substrates (e.g., rosuvastatin) that may cause severe adverse reactions. If necessary, monitor for adverse reactions and adjust the dose of the concomitant drug.

Zongertinib Use in Special Populations

Pregnant and Lactating Women

Pregnancy Risk: Animal studies have shown that Zongertinib can cause fetal malformations; it is contraindicated in pregnant women. Women of childbearing age should use effective contraceptive measures during treatment and for 2 weeks after the last dose.

Lactation: Breastfeeding is prohibited during treatment and for 2 weeks after the last dose.

Patients with Hepatic or Renal Impairment

Mild Hepatic Impairment (AST > ULN and bilirubin ≤ ULN) or Mild Renal Impairment (eGFR 60-90 mL/min): No dose adjustment is required.

Moderate to Severe Hepatic or Renal Impairment: There is currently no clear data available; careful assessment is required.