Histologically or cytologically confirmed locally advanced or metastatic NSCLC
Documented disease progression after treatment with at least one prior systemic therapy for advanced disease
Documented HER2 activating mutation
Expected minimum life expectancy of 12 weeks
Performance status of 0 or 1
Participants must be able to take oral medication
Blood test results within certain ranges
Adequate coagulation as assessed by lab tests or on stable anticoagulation treatment
Adequate cardiac function
Negative serum pregnancy test in women of childbearing potential within 72 hours of the first dose
Ability to receive prescription of loperamide from the treating physician
You may not be if
Investigational agent or anticancer therapy within 2 weeks prior to planned start of sevabertinib or 5 half-lives, whichever is shorter, and without recovery of clinically significant toxicities from that therapy
Prior progression while receiving approved or investigational tyrosine kinase inhibitors targeting HER2
Symptomatic or unstable brain metastases
Treatment with immunotherapy ≤ 28 days prior to the first dose of IMP
Past medical history of Grade ≥2 ILD, drug-induced interstitial lung disease
Inability to discontinue treatment with a strong CYP3A4 inhibitor or inducer prior to start of treatment initiation
Any uncontrolled intercurrent illness or condition including, but not limited to, uncompensated respiratory, cardiac, hepatic, or renal disease, ongoing or active infection (including active clinical tuberculosis), renal transplant or psychiatric illness/social situations that would limit compliance
