Zongertinib

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. 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.

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.

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.

None. None.

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. Interstitial Lung Disease/Pneumonitis: Monitor for new or worsening symptoms indicative of ILD/pneumonitis (e.g., dyspnea, cough, fever). Embryo-Fetal Toxicity: Can cause fetal harm. Advise patients of the potential risk to a fetus and to use effective contraception.

The following adverse reactions are discussed in greater detail in other sections of the labeling: Hepatotoxicity Left Ventricular Dysfunction Interstitial Lung Disease/Pneumonitis Most common adverse reactions (≥ 20%) are diarrhea, rash, hepatotoxicity, fatigue, nausea, musculoskeletal pain, and upper respiratory tract infection. 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.

Strong CYP3A Inducers: Avoid concomitant use with strong CYP3A inducers. If concomitant use cannot be avoided, increase HERNEXEOS dose. BCRP Substrates: Avoid concomitant use with certain BCRP substrates where minimal concentration increase may lead to serious adverse reactions and consider alternative therapies. If concomitant use cannot be avoided, monitor patients closely for adverse reactions and follow recommendations provided in the BCRP substrate approved product labeling. For other BCRP substrates, monitor for increased adverse reactions and adjust the dosages of those substrates as clinically appropriate.

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.