TABRECTA

Clinical summary

Indications and usage 1 INDICATIONS AND USAGE TABRECTA is indicated for the treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have a mutation that leads to mesenchymal-epithelial transition (MET) exon 14 skipping as detected by an FDA-approved test. TABRECTA is a kinase inhibitor indicated for the treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have a mutation that leads to mesenchymal-epithelial transition (MET) exon 14 skipping as detected by an FDA-approved test. Dosage and administration 2 DOSAGE AND ADMINISTRATION Select patients for treatment with TABRECTA based on presence of a mutation that leads to MET exon 14 skipping. ( 2.1 ) Recommended Dosage : 400 mg orally twice daily with or without food. ( 2.2 ) 2.1 Patient Selection Select patients for treatment with TABRECTA based on the presence of a mutation that leads to MET exon 14 skipping in tumor or plasma specimens [see Clinical Studies (14)] . If a mutation that leads to MET exon 14 skipping is not detected in a plasma specimen, test tumor tissue if feasible. Information on FDA-approved tests is available at: http://www.fda.gov/CompanionDiagnostics . 2.2 Recommended Dosage The recommended dosage of TABRECTA is 400 mg orally twice daily with or without food. Swallow TABRECTA tablets whole. Do not break, crush or chew the tablets. If a patient misses or vomits a dose, instruct the patient not to make up the dose, but to take the next dose at its scheduled time. 2.3 Dosage Modifications for Adverse Reactions The recommended dose reductions for the management of adverse reactions are listed in Table 1. Table 1: Recommended TABRECTA Dose Reductions for Adverse Reactions Dose reduction Dose and schedule First 300 mg orally twice daily Second 200 mg orally twice daily Permanently discontinue TABRECTA in patients who are unable to tolerate 200 mg orally twice daily. The recommended dosage modifications of TABRECTA for adverse reactions are provided in Table 2. Table 2: Recommended TABRECTA Dosage Modifications for Adverse Reactions Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; ILD, interstitial lung disease; ULN, upper limit of normal. Grading according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Adverse reaction Severity Dosage modification Interstitial Lung Disease (ILD)/Pneumonitis [see Warnings and Precautions (5.1)] Any grade Permanently discontinue TABRECTA. Increased ALT and/or AST without increased total bilirubin [see Warnings and Precautions (5.2)] Grade 3 Withhold TABRECTA until recovery to baseline ALT/AST. If recovered to baseline within 7 days, then resume TABRECTA at the same dose; otherwise resume TABRECTA at a reduced dose. Grade 4 Permanently discontinue TABRECTA. Increased ALT and/or AST with increased total bilirubin in the absence of cholestasis or hemolysis [see Warnings and Precautions (5.2)] ALT and/or AST greater than 3 times ULN with total bilirubin greater than 2 times ULN Permanently discontinue TABRECTA. Increased total bilirubin without concurrent increased ALT and/or AST [see Warnings and Precautions (5.2)] Grade 2 Withhold TABRECTA until recovery to baseline bilirubin. If recovered to baseline within 7 days, then resume TABRECTA at the same dose; otherwise resume TABRECTA at a reduced dose. Grade 3 Withhold TABRECTA until recovery to baseline bilirubin. If recovered to baseline within 7 days, then resume TABRECTA at a reduced dose; otherwise permanently discontinue TABRECTA. Grade 4 Permanently discontinue TABRECTA. Increased lipase or amylase [see Warnings and Precautions (5.3)] Grade 3 Withhold TABRECTA until ≤ Grade 2 or baseline. If recovered to baseline or ≤ Grade 2 within 14 days, resume TABRECTA at a reduced dose; otherwise permanently discontinue TABRECTA. Grade 4 Permanently discontinue TABRECTA. Pancreatitis [see Warnings and Precautions (5.3)] Grade 3 or Grade 4 Permanently discontinue TABRECTA. Hypersensitivity [see Warnings and Precautions (5.4)] All Grades If hypersensitivity is suspected based on clinical judgment, withhold TABRECTA until resolution of the event. Permanently discontinue TABRECTA in patients who develop serious hypersensitivity reactions. Other adverse reactions [see Adverse Reactions (6.1)] Grade 2 Maintain dose level. If intolerable, consider withholding TABRECTA until resolved, then resume TABRECTA at a reduced dose. Grade 3 Withhold TABRECTA until resolved, then resume TABRECTA at a reduced dose. Grade 4 Permanently discontinue TABRECTA. Warnings and cautions 5 WARNINGS AND PRECAUTIONS Interstitial Lung Disease (ILD)/Pneumonitis : Monitor for new or worsening pulmonary symptoms indicative of ILD/pneumonitis. Permanently discontinue TABRECTA in patients with ILD/pneumonitis. ( 2.3 , 5.1 ) Hepatotoxicity : Monitor liver function tests. Withhold, dose reduce, or permanently discontinue TABRECTA based on severity. ( 2.3 , 5.2 ) Pancreatic Toxicity