Selpercatinib

　　【Indications】

　　This product is a selective kinase inhibitor indicated for the treatment of:

　　Adult patients with locally advanced or metastatic RET fusion-positive non-small cell lung cancer(NSCLC);

　　Adult and pediatric patients aged 12 years and older with advanced or metastatic RET-mutant medullary thyroid carcinoma(MTC)who require systemic therapy;

　　Adult and pediatric patients aged 12 years and older with advanced or metastatic RET fusion-positive thyroid cancer who require systemic therapy and are refractory to radioactive iodine treatment;

　　Adult patients with locally advanced or metastatic solid tumors harboring a RET gene fusion who have progressed on or following prior systemic therapy,or for whom no satisfactory alternative treatment options are available.

　　【Recommended Dosage】

　　Prior to initiating RETEVMO therapy,the presence of a RET gene fusion(in NSCLC or thyroid cancer)or a specific RET gene mutation(in MTC)should be confirmed using a validated diagnostic assay.

　　The recommended dosage for adult and pediatric patients aged 12 years and older is determined by body weight:

　　①Body weight less than 50 kg:120 mg orally,twice daily;

　　②Body weight 50 kg or greater:160 mg orally,twice daily.

　　Treatment should continue until disease progression or unacceptable toxicity occurs.

　　【Adverse Reactions】

　　The most frequently observed adverse reactions,including laboratory abnormalities,occurring in≥25%of patients include:elevated aspartate aminotransferase(AST),elevated alanine aminotransferase(ALT),hyperglycemia,leukopenia,hypoalbuminemia,hypocalcemia,dry mouth,diarrhea,elevated creatinine,elevated alkaline phosphatase,hypertension,fatigue,edema,thrombocytopenia,hypercholesterolemia,rash,hyponatremia,and constipation.

　　【Pharmacology】

　　This product is a multi-target kinase inhibitor.Selpercatinib demonstrates inhibitory activity against wild-type RET and multiple mutant RET variants,as well as VEGFR1 and VEGFR3,with IC50 values ranging from 0.92 nM to 67.8 nM.In additional in vitro enzymatic assays,selpercatinib also inhibits FGFR1,FGFR2,and FGFR3 at higher concentrations that remain clinically achievable.Cell-based assays indicate that selpercatinib inhibits RET at approximately 60-fold lower concentrations than those required for FGFR1 and FGFR2 inhibition,and at approximately 8-fold lower concentrations than those needed for VEGFR3 inhibition,reflecting its high selectivity for RET.

　　Certain point mutations in the RET gene or chromosomal rearrangements resulting in in-frame fusions between RET and various partner genes can produce constitutively activated chimeric RET fusion proteins that function as oncogenic drivers by promoting tumor cell proliferation.In both in vitro and in vivo tumor models,selpercatinib has demonstrated antitumor activity in cells harboring constitutively activated RET proteins generated by gene fusions and mutations,including CCDC6-RET,KIF5B-RET,RET V804M,and RET M918T.Furthermore,selpercatinib exhibited intracranial antitumor efficacy in murine models bearing intracranially implanted patient-derived RET fusion-positive tumors.

　　【Storage】

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