HERNEXEOS Zongertinib

Indications and Usage

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 detected by an FDA-approved test, and who have received prior systemic therapy.
This indication is approved under accelerated approval based on objective response rate (ORR) and duration of response (DOR). Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s).

Dosage and Administration
Patient Selection‌: Confirm presence of HER2 (ERBB2) tyrosine kinase domain activating mutations in tumor specimen prior to treatment.
Recommended Dosage based on body weight‌:
＜ 90 kg: 120 mg orally once daily
≥ 90 kg: 180 mg orally once daily
Administer until disease progression or unacceptable toxicity. May take with or without food. Swallow whole tablet, do not chew, crush or split.
Dose modification‌: Interrupt, reduce dose, or permanently discontinue based on severity of adverse reactions (including hepatotoxicity, left ventricular dysfunction, interstitial lung disease/pneumonitis).
Drug Interaction with strong CYP3A inducers‌: Avoid concomitant use. If unavoidable, increase dose: ＜ 90 kg from 120 mg to 240 mg once daily; ≥ 90 kg from 180 mg to 360 mg once daily. Resume original dose 7 to 14 days after discontinuation of the CYP3A inducer.
Warnings and Precautions
Hepatotoxicity‌: Severe and life-threatening hepatotoxicity can occur. Monitor ALT, AST and total bilirubin before initiation, every 2 weeks for the first 12 weeks of treatment, then monthly thereafter. Interrupt, reduce dose or permanently discontinue based on severity.
Left Ventricular Dysfunction‌: Can cause symptomatic left ventricular systolic dysfunction. Assess left ventricular ejection fraction (LVEF) before initiation and monitor periodically during treatment. Interrupt, reduce dose or permanently discontinue based on severity.
Interstitial Lung Disease (ILD)/Pneumonitis‌: Severe and fatal ILD/pneumonitis can occur. Monitor for new or worsening symptoms indicative of ILD/pneumonitis. Interrupt treatment promptly and evaluate. Permanently discontinue for ILD of grade 3/4 or recurrent ILD.
Embryo-Fetal Toxicity‌: Can cause fetal harm. Advise patients of potential risk to fetus and to use effective contraception during treatment and for 2 weeks after the last dose.