Sunvozertinib

1. INDICATIONS AND USAGE ZEGFROVY is 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).

Sunvozertinib is a kinase inhibitor of the epidermal growth factor receptor (EGFR) that binds to and inhibits EGFR exon 20 insertion mutations at similar concentrations as wild-type EGFR. In cultured cell models, sunvozertinib inhibited EGFR phosphorylation in cells expressing different EGFR exon 20 insertion mutation variants at approximately 2- to 10-fold lower concentrations than wild-type EGFR signaling inhibition. Sunvozertinib exhibited anti-tumor activity against xenograft models of NSCLC with EGFR exon 20 insertion mutations.

2. DOSAGE AND ADMINISTRATION Recommended dosage: 200 mg orally once daily taken with food. Patient Selection Select patients for treatment with ZEGFROVY for locally advanced or metastatic NSCLC based on the presence of EGFR exon 20 insertion mutations in tumor tissue. Information on FDA-approved tests is available at: http://www.fda.gov/CompanionDiagnostics.

4. CONTRAINDICATIONS None. None.

5. 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.

6. ADVERSE REACTIONS The following adverse reactions are described elsewhere in the labeling: Interstitial Lung Disease/Pneumonitis Gastrointestinal Adverse Reactions Dermatologic Adverse Reactions Ocular Toxicity 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.

7. 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.

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