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

Screening of Eligible Populations

The use of Zongertinib requires confirmation of activating mutations in the tyrosine kinase domain of HER2 (ERBB2) in the tumor through an FDA-approved test.

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

Administration Regimen

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

Administration Method: Take orally once daily, either with food or on an empty stomach. Swallow the tablet whole; do not break, crush, or chew it.

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

Management of Missed Dose: If the time since the missed dose is ≤12 hours, the missed dose can be taken. If more than 12 hours have passed, skip the current dose and take the next dose as scheduled.

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

Dose Adjustment of Zongertinib

Adjustment Based on Adverse Reactions

Hepatotoxicity: In case of grade 3 elevation of ALT/AST or grade 4 elevation of ALT/AST without bilirubin elevation, interrupt medication until indicators return to ≤grade 1, then resume treatment at a reduced dose. If grade 4 bilirubin elevation occurs, or ALT/AST ≥3 times the upper limit of normal (ULN) accompanied by bilirubin ≥2 times the ULN, permanent discontinuation of the medication is required.

Left Ventricular Dysfunction: When LVEF decreases to 40-50% and drops by 10-19% from baseline, interrupt medication. Resume treatment at the original dose after recovery within 4 weeks. If LVEF <40% or decreases by ≥20% from baseline, reduce the dose or discontinue the medication permanently.

Interstitial Lung Disease (ILD)/Pneumonia: For grade 2 symptoms, suspend medication until remission, then resume at a reduced dose. For grade 3 or 4 ILD/pneumonia, permanent discontinuation of the medication is required.

Diarrhea: If grade 2 diarrhea persists for ≥2 days or grade 3 or above diarrhea occurs, interrupt medication. Resume treatment at a reduced dose after recovery. If symptoms do not remit to ≤grade 1 within 14 days, permanent discontinuation of the medication is required.

Adjustment Due to Drug Interactions

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

BCRP Substrate Drugs: Avoid concomitant use of BCRP substrates that may cause severe adverse reactions (e.g., rosuvastatin). If necessary, monitor for adverse reactions and adjust the dose of the co-administered 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 potential must 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 Impairment or Renal Impairment: There is currently no clear data available; careful evaluation is required.