Initial US Approval:
2025
Key Clinical Studies:
SOHO-01 (NCT05099172)
Drug Class/Description:
Kinase inhibitor
Indications and Usage:
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-approved test, and who have received a 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 a confirmatory trial.
Dosage and Administration:
- 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.
Dosage Forms and Strengths:
Tablets: 10 mg of sevabertinib.
Contraindications:
None.
Warnings and Precautions:
- 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 administration of HYRNUO, every 2 weeks during the first month, and then monthly thereafter as clinically indicated, with more frequent testing in patients who develop transaminase elevations. Interrupt, reduce the dose, or permanently discontinue HYRNUO based on severity.
- 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.
- Ocular Toxicity: Promptly refer patients presenting with new or worsening eye symptoms to an ophthalmologist. Interrupt, reduce the dose or permanently discontinue HYRNUO based on severity.
- Pancreatic Enzyme Elevation: Monitor amylase and lipase regularly during treatment. Interrupt, reduce the dose, or permanently discontinue HYRNUO based on severity.
- Embryo-fetal toxicity: Can cause fetal harm. Advise patients of the potential risk to a fetus and to use effective contraception.
Adverse Reactions:
- Most common adverse reactions (>20%): diarrhea, rash, paronychia, stomatitis, and nausea.
- Most common Grade 3 or 4 laboratory abnormalities (≥2%): decreased potassium, increased lipase, decreased lymphocytes, decreased sodium, increased amylase, increased ALT increased, and increased AST increased.
Drug Interactions:
- Strong CYP3A Inhibitors: Avoid concomitant use with strong CYP3A inhibitors. 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 with strong or moderate CYP3A inducers.
- Certain CYP3A Substrates: Avoid concomitant use with CYP3A substrates where minimal increases in 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 Pgp substrates where minimal increases in concentration may lead to serious adverse reactions
Use in Specific Populations:
Lactation: Advise not to breastfeed.
Adapted From:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/219972s000lblCorrected.pdf
Every health-care provider should make their own determination regarding specific safe and appropriate patient care practices, including drug dosages and indications. The provider should always consult the most recent prescribing/product information. FDA Focus information is not guaranteed to be accurate, complete, or current. JADPRO and its editors, authors, reviewers, and commentators cannot be held responsible for any liability incurred as a consequence of the application of any of the information listed within.
