Teponi (Tepotinib)

Tepotinib is a kinase inhibitor directed against MET, including variants with exon 14 skipping - it inhibits MET phosphorylation and subsequent downstream signaling pathways in order to inhibit tumor cell proliferation, anchorage-independent growth, and migration of MET-dependent tumor cells.

Non–Small Cell Lung Cancer

Indicated for metastatic non–small cell lung cancer (NSCLC) in adults harboring mesenchymal-epithelial transition (MET) exon 14 (ex14) skipping alterations

450 mg PO qDay

Continue until disease progression or unacceptable toxicity

Dosage Modifications

Recommended dose reduction to manage adverse reactions: 225 mg PO qDay

Permanently discontinue if unable to tolerate 225 mg PO qDay

Interstitial lung disease (ILD)/ pneumonitis

• Suspected ILD (any grade): Withhold
• Confirmed ILD: Permanently discontinue

Increased AST/ALT and/or total bilirubin

• Grade 3 increased AST/ALT without increased total bilirubin

  • Withhold until recovery to baseline ALT/AST
  • If recovered to baseline ≤7 days, resume at same dose; otherwise, resume at a reduced dose

• Grade 3 increased total bilirubin without concurrent increased AST/ALT

  • Withhold until recovery to baseline total bilirubin
  • If recovered to baseline ≤7 days, resume at reduced dose; otherwise, permanently discontinue

• Permanently discontinue

  • Grade 4 increased ALT/AST without increased total bilirubin
  • ALT/AST >3x ULN with total bilirubin >2x ULN without cholestasis or hemolysis
  • Grade 4 increased total bilirubin without concurrent increased AST/ALT

Other adverse reactions

• Grade 2: Maintain dose; if intolerable, consider withholding until resolved, then resume at reduced dose
• Grade 3: Withhold until resolved, then resume at reduced dose
• Grade 4: Permanently discontinue

Renal impairment

• Mild-to-moderate (CrCl 30-89 mL/min): No dosage adjustment necessary
• Severe (CrCl <30 mL/min): Recommended dose not established

Hepatic impairment

• Mild-to-moderate (Child-Pugh Class A or B): No dosage adjustment necessary
• Severe (Child-Pugh Class C): Pharmacokinetics and safety not studied