HERNEXEOS

2 DOSAGE AND ADMINISTRATION Select patients for treatment with HERNEXEOS based on the presence of HER2 (ERBB2) tyrosine kinase domain activating mutations. ( 2.1 ) The recommended dosage of HERNEXEOS is based on body weight: ( 2.2 ) Patients weighing less than 90 kg: 120 mg ( 2.2 ) Patients weighing 90 kg or greater: 180 mg ( 2.2 ) Take HERNEXEOS orally once daily with or without food until disease progression or unacceptable toxicity. ( 2.2 ) 2.1 Patient Selection Select patients for treatment of unresectable or metastatic NSCLC based on the presence of HER2 (ERBB2) tyrosine kinase domain activating mutations in tumor specimens [see Clinical Studies (14) ] . Information on FDA-authorized tests for HER2 (ERBB2) tyrosine kinase domain activating mutations is available at: http://www.fda.gov/CompanionDiagnostics. 2.2 Recommended Dosage and Administration The recommended dosage of HERNEXEOS is based on body weight: Patients weighing less than 90 kg: 120 mg Patients weighing 90 kg or greater: 180 mg Take HERNEXEOS orally once daily with or without food until disease progression or unacceptable toxicity. Swallow HERNEXEOS tablets whole with water. Do not split, crush, or chew tablets. Missed Dose If a dose is missed within 12 hours, take the dose. If a dose is missed by more than 12 hours, skip the missed dose and take the next scheduled dose. Vomited Dose If a dose is vomited, do not take an additional dose. Take the next dose at the regularly scheduled time. 2.3 Dosage Modifications for Adverse Reactions The recommended dose reductions for adverse reactions are presented in Table 1. Table 1 Recommended HERNEXEOS Dose Reductions for Adverse Reactions Current HERNEXEOS Dose First Reduction Second Reduction 180 mg 120 mg 60 mg 120 mg 60 mg Permanently discontinue Permanently discontinue HERNEXEOS in patients who are unable to tolerate 60 mg once daily. The recommended dosage modifications for adverse reactions are presented in Table 2. Table 2 Recommended HERNEXEOS Dosage Modifications for Adverse Reactions Adverse Reaction Severity* Dosage Modification ALT = alanine aminotransferase; AST = aspartate aminotransferase; ULN = upper limit of normal *Based on Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 Hepatotoxicity [see Warnings and Precautions (5.1) ] Grade 3 or 4 ALT and/or AST without increased total bilirubin Interrupt HERNEXEOS until recovered to ≤ Grade 1 or baseline. Resume HERNEXEOS at reduced dose level. Grade 3 total bilirubin Interrupt HERNEXEOS until recovered to ≤ Grade 1 or baseline. Resume HERNEXEOS at reduced dose level. Grade 4 total bilirubin Permanently discontinue HERNEXEOS. ALT or AST ≥ 3× ULN with total bilirubin ≥ 2× ULN Permanently discontinue HERNEXEOS. Left Ventricular Dysfunction [see Warnings and Precautions (5.2) ] LVEF 40 to 50% and decrease from baseline of 10 to 19% Interrupt HERNEXEOS until recovered to ≤ Grade 1 or within 10% from baseline. If recovered to ≤ Grade 1 in ≤ 4 weeks, resume HERNEXEOS at the same dose level. If not recovered to ≤ Grade 1 within 4 weeks, permanently discontinue HERNEXEOS. LVEF 20 to 39% or ≥ 20% decrease from baseline Interrupt HERNEXEOS until recovered to ≤ Grade 1 or within 10% from baseline. If recovered to ≤ Grade 1 in ≤ 4 weeks, resume HERNEXEOS at the reduced dose level. If not recovered to ≤ Grade 1 within 4 weeks, permanently discontinue HERNEXEOS. Symptomatic Congestive Heart Failure Permanently discontinue HERNEXEOS. Interstitial Lung Disease/Pneumonitis [see Warnings and Precautions (5.3) ] Grade 2 Withhold HERNEXEOS until resolution. Resume HERNEXEOS at reduced dose level. Permanently discontinue HERNEXEOS for recurrent ILD/pneumonitis. Grade 3 or Grade 4 Permanently discontinue HERNEXEOS. Diarrhea [see Adverse Reactions (6.1) ] Grade 2 Maintain HERNEXEOS dose. Initiate anti-diarrheal treatment. Grade 2 lasting ≥ 2 days despite anti-diarrheal treatment Interrupt HERNEXEOS until recovered to ≤ Grade 1. Resume HERNEXEOS at reduced dose level. Grade 3 or Grade 4 Interrupt HERNEXEOS until recovered to ≤ Grade 1. Resume HERNEXEOS at reduced dose level. Permanently discontinue HERNEXEOS if diarrhea does not resolve to ≤ Grade 1 within 14 days, despite optimal supportive care (including anti-diarrheal treatment) and treatment interruption. Other Adverse Reactions [see Adverse Reactions (6.1) ] Grade 3 Interrupt HERNEXEOS until recovered to ≤ Grade 1 or baseline. Resume HERNEXEOS at reduced dose level. Grade 4 Permanently discontinue HERNEXEOS. 2.4 Dosage Modifications for Drug Interactions Strong CYP3A Inducers Avoid concomitant use of strong CYP3A inducers with HERNEXEOS . If concomitant use cannot be avoided, increase the HERNEXEOS dose based on body weight [see Drug Interactions (7.1) ] : Patients weighing less than 90 kg: from 120 mg to 240 mg Patients weighing 90 kg or greater: from 180 mg to 360 mg After discontinuing a CYP3A inducer, resume the HERNEXEOS dose (7 to 14 days after discontinuing the CYP3A inducer) that was taken prior to initiating the CYP3A inducer.

See official label

1 INDICATIONS AND USAGE HERNEXEOS is indicated for the treatment of adult patients with unresectable or metastatic non-squamous non-small cell lung cancer (NSCLC) whose tumors have HER2 (ERBB2) tyrosine kinase domain activating mutations, as detected by an FDA-authorized test [see Dosage and Administration (2.1) ] .