Initial US Approval:
2025
Key Clinical Studies:
WU-KONG1B (NCT03974022)
Drug Class/Description:
Irreversible EGFR tyrosine kinase inhibitor
Indications and Usage:
ZEGFROVY is a kinase inhibitor indicated for the treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutations, as detected by an FDA-approved test, whose disease has progressed on or after platinum-based chemotherapy.
This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s).
Dosage and Administration:
Recommended dosage: 200 mg orally once daily taken with food.
Dosage Forms and Strengths:
Tablets: 150 mg and 200 mg.
Contraindications:
None.
Warnings and Precautions:
- Interstitial Lung Disease (ILD)/Pneumonitis: Monitor patients for new or worsening pulmonary symptoms indicative of ILD/pneumonitis. Immediately withhold ZEGFROVY in patients with suspected ILD/pneumonitis and permanently discontinue ZEGFROVY if ILD/pneumonitis is confirmed.
- Gastrointestinal Adverse Reactions: Administer ZEGFROVY with food to reduce gastrointestinal adverse reactions. Monitor patients for nausea, vomiting and diarrhea and provide supportive care, including anti-diarrheals, anti-emetics, or fluid replacement, as indicated. Withhold, reduce the dose, or permanently discontinue ZEGFROVY based on severity.
- Dermatologic Adverse Reactions: Monitor patients for rash and dermatologic adverse reactions. Instruct patients to use alcohol-free (e.g., isopropanol-free, ethanol-free) emollient cream during treatment with ZEGFROVY and to avoid the use of irritating skin products (e.g., products containing retinol or retinoic acid, benzoyl peroxides). Withhold, reduce the dose, or permanently discontinue ZEGFROVY based on severity.
- Ocular Toxicity: Promptly refer patients presenting with eye symptoms suggestive of keratitis to an ophthalmologist. Advise discontinuation of contact lenses until ocular symptoms are evaluated. Withhold, reduce the dose, or permanently discontinue ZEGFROVY based on severity.
- Embryo-Fetal Toxicity: Can cause fetal harm. Advise females of reproductive potential of the potential risk to a fetus and to use effective non-hormonal contraception.
Adverse Reactions:
- The most common (≥20%) adverse reactions were: diarrhea, rash, decreased appetite, stomatitis, fatigue, nausea, paronychia, vomiting, constipation, musculoskeletal pain, pruritus, dry skin, urinary tract infection, abdominal pain and decreased weight.
- The most common (≥2%) Grade 3 or 4 laboratory abnormalities were: decreased lymphocytes, increased lipase, decreased hemoglobin, increased amylase, increased creatine kinase, decreased neutrophils, decreased potassium, increased aspartate aminotransferase, increased alanine aminotransferase, decreased sodium, increased magnesium, and increased alkaline phosphatase.
Drug Interactions:
- Strong CYP3A Inhibitors: Avoid concomitant use. If concomitant use cannot be avoided, reduce ZEGFROVY dose.
- Strong and Moderate CYP3A Inducers: Avoid concomitant use. If concomitant use cannot be avoided, increase ZEGFROVY dose.
- P-gp or BCRP Substrates: Monitor for increased adverse reactions during concomitant use with ZEGFROVY.
- Hormonal Contraceptives: Avoid concomitant use.
Use in Specific Populations:
Lactation: Advise not to breastfeed.
Adapted From:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/219839s000lbl.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.
