Sevabertinib

HYRNUO is indicated for the treatment of adult patients with locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) whose tumors have HER2 ( ERBB2 ) tyrosine kinase domain (TKD) activating mutations, as detected by an FDA-authorized test. 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 a confirmatory trial. HYRNUO is a kinase inhibitor indicated for the treatment of adult patients with locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) whose tumors have HER2 ( ERBB2 ) tyrosine kinase domain (TKD) activating mutations, as detected by an FDA-authorized test.

Sevabertinib is a reversible kinase inhibitor of human epidermal growth factor receptor 2 (HER2). It also exhibits activity against epidermal growth factor receptor (EGFR). In vitro, sevabertinib inhibited the phosphorylation of HER2 and downstream signaling in cancer cells with HER2 alterations and proliferation of cancer cells overexpressing wild-type HER2 or harboring HER2 mutations. In vivo, sevabertinib demonstrated antitumor activity in subcutaneous mouse xenograft models derived from human NSCLC tumors harboring an activating HER2 exon 20 mutation.

Select patients for treatment with HYRNUO based on the presence of HER2 ( ERBB2 ) TKD activating mutations. Recommended Dosage: 20 mg orally twice daily with food until disease progression or unacceptable toxicity. Swallow tablets whole.

None. None.

Diarrhea: At the first sign of diarrhea or increased bowel movement frequency, instruct patients to start an antidiarrheal treatment, and to increase their fluid and electrolyte intake. Interrupt, reduce the dose, or permanently discontinue HYRNUO based on severity. Hepatotoxicity: Monitor liver function tests including ALT, AST, and total bilirubin at baseline prior to the first administration of HYRNUO, every 2 weeks for the first month, and then monthly thereafter as clinically indicated, with more frequent testing in patients who develop transaminase elevations. Interstitial Lung Disease (ILD)/Pneumonitis: Monitor patients for new or worsening symptoms indicative of ILD/pneumonitis (e.g., dyspnea, cough, fever). Discontinue HYRNUO upon confirmation of ILD/pneumonitis.

The following clinically significant adverse reactions are discussed in greater detail in other sections of the labeling: Diarrhea Hepatotoxicity Interstitial Lung Disease (ILD)/Pneumonitis Left Ventricular Dysfunction Ocular Toxicity Pancreatic Enzyme Elevation Most common (>20%) adverse reactions: diarrhea, rash, paronychia, nausea, vomiting and stomatitis. Most common (≥2%) Grade 3 or 4 laboratory abnormalities: decreased potassium, increased lipase, decreased phosphate, decreased lymphocyte count, decreased sodium, increased amylase, decreased hemoglobin, increased ALT, increased AST and decreased calcium.

Strong CYP3A Inhibitors: Avoid concomitant use. If concomitant use cannot be avoided, reduce HYRNUO dosage. Moderate CYP3A Inhibitors: Monitor patients for increased HYRNUO-associated adverse reactions. Strong and Moderate CYP3A Inducers: Avoid concomitant use. Certain CYP3A Substrates: Avoid concomitant use where minimal increases in the concentration may lead to serious adverse reactions unless otherwise recommended in the Prescribing Information of the CYP3A substrate. Certain P-gp Substrates: Refer to the Prescribing Information for P-gp substrates where minimal increases in the concentration may lead to serious adverse reactions.

Store at 20°C to 25°C (68°F to 77°F), excursions permitted between 15°C to 30°C (59°F to 86°F).