General MedicationsORALHigh Alert

HYRNUO

SEVABERTINIB

Standard Dose

2 DOSAGE AND ADMINISTRATION Select patients for treatment with HYRNUO based on the presence of HER2 ( ERBB2 ) TKD activating mutations. ( 2.1 ) Recommended Dosage : 20 mg orally twice daily with food until disease progression or unacceptable toxicity. Swallow tablets whole. ( 2.2 ) 2.1 Patient Selection Select patients for treatment of locally advanced or metastatic non-squamous NSCLC based on the presence of HER2 ( ERBB2 ) TKD activating mutations in tumor specimens [see Clinical Studies (14) ] . Information on FDA-approved tests is available at http://www.fda.gov/CompanionDiagnostics. 2.2 Recommended Dosage The recommended dosage of HYRNUO is 20 mg orally twice daily with food, until disease progression or unacceptable toxicity [see Clinical Pharmacology (12.3) ] . Swallow tablets whole. Do not cut, crush, or chew tablets. Missed Dose If a dose is missed, take the missed dose as soon as you remember prior to the next scheduled dose. Do not take 2 doses at the same time to make up for the missed dose. Vomited Dose If a dose is vomited, do not take an additional dose. Resume dosing at the next scheduled time. 2.3 Dosage Modifications for Adverse Reactions The recommended dosage reductions for adverse reactions are provided in Table 1. Table 1: Recommended HYRNUO Dosage Reductions for Adverse Reactions Dose Reduction Dosage Modification First 10 mg twice daily Second 10 mg once daily Permanently discontinue HYRNUO in patients who are unable to tolerate 10 mg once daily. The recommended dosage modifications for adverse reactions are provided in Table 2. Table 2: Recommended HYRNUO Dosage Modifications for Adverse Reactions Adverse Reaction Severity Grades based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 5.0. Dosage Modification Diarrhea [see Warnings and Precautions (5.1) ] Intolerable Grade 2 or Grade 3 Interrupt HYRNUO until recovery to Grade ≤1. Resume HYRNUO at the same dose or the next lower dose. For recurrence, resume HYRNUO at the next lower dose. Grade 4 Permanently discontinue HYRNUO. Hepatotoxicity [see Warnings and Precautions (5.2) ] Grade 2, 3 or 4 ALT and/or AST without increased total bilirubin or Grade 3 total bilirubin Interrupt HYRNUO until recovery to Grade ≤1 or baseline. Resume HYRNUO at the next lower dose. ALT or AST ≥ 3× ULN with total bilirubin ≥ 2× ULN or Grade 4 total bilirubin Permanently discontinue HYRNUO. Interstitial lung disease (ILD)/pneumonitis [see Warnings and Precautions (5.3) ] Any Grade Permanently discontinue HYRNUO. Ocular toxicity [see Warnings and Precautions (5.4) ] Grade 2 Interrupt HYRNUO until recovery to Grade ≤1. Resume HYRNUO at the next lower dose. For recurrence, permanently discontinue HYRNUO. Grade 3 or Grade 4 Permanently discontinue HYRNUO. Pancreatic Enzyme Elevation [see Warnings and Precautions (5.5) ] Grade 3 Interrupt HYRNUO until recovery to Grade ≤2 or baseline. Resume HYRNUO at the next lower dose. Grade 4 Permanently discontinue HYRNUO. Other adverse reactions [see Adverse Reactions (6.1) ] Intolerable or recurrent Grade 2 or Grade 3 Interrupt HYRNUO until recovery to Grade ≤1. Resume HYRNUO at the same dose or the next lower dose. For recurrence, resume HYRNUO at the next lower dose. Grade 4 Permanently discontinue HYRNUO. 2.4 Dosage Modifications for Strong CYP3A Inhibitors Avoid concomitant use of strong CYP3A inhibitors. If concomitant use cannot be avoided, reduce HYRNUO dosage as shown in Table 3. After the CYP3A inhibitor has been discontinued for 3 to 5 elimination half-lives, resume the HYRNUO dosage that was used prior to initiating the inhibitor [see Drug Interactions (7.1) ]. Table 3: Recommended HYRNUO Dosage Modifications for Concomitant Use with Strong CYP3A Inhibitors Current Dosage Recommended Dosage 20 mg twice daily 10 mg twice daily 10 mg twice daily 10 mg once daily 10 mg once daily Withhold HYRNUO until strong CYP3A inhibitor is discontinued

Max Dose

See official label

Primary Use

1 INDICATIONS AND USAGE HYRNUO is indicated for the treatment of adult patients with locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) whose tumors have HER2 ( ERBB2 ) tyrosine kinase domain (TKD) activating mutations, as detected by an FDA-approved test [see Dosage and Administration (2.1) ] , and who have received a prior systemic therapy.

Summary

This indication is approved under accelerated approval based on objective response rate (ORR) and duration of response (DOR) [see Clinical Studies (14) ] .

Structured Monograph

Clinical summary

Indications and usage 1 INDICATIONS AND USAGE HYRNUO is indicated for the treatment of adult patients with locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) whose tumors have HER2 ( ERBB2 ) tyrosine kinase domain (TKD) activating mutations, as detected by an FDA-approved test [see Dosage and Administration (2.1) ] , and who have received a prior systemic therapy. This indication is approved under accelerated approval based on objective response rate (ORR) and duration of response (DOR) [see Clinical Studies (14) ] . Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. HYRNUO is a kinase inhibitor indicated for the treatment of adult patients with locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) whose tumors have HER2 ( ERBB2 ) tyrosine kinase domain (TKD) activating mutations, as detected by an FDA-approved test, and who have received a prior systemic therapy. ( 1 ) This indication is approved under accelerated approval based on objective response rate (ORR) and duration of response (DOR). Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. Dosage and administration 2 DOSAGE AND ADMINISTRATION Select patients for treatment with HYRNUO based on the presence of HER2 ( ERBB2 ) TKD activating mutations. ( 2.1 ) Recommended Dosage : 20 mg orally twice daily with food until disease progression or unacceptable toxicity. Swallow tablets whole. ( 2.2 ) 2.1 Patient Selection Select patients for treatment of locally advanced or metastatic non-squamous NSCLC based on the presence of HER2 ( ERBB2 ) TKD activating mutations in tumor specimens [see Clinical Studies (14) ] . Information on FDA-approved tests is available at http://www.fda.gov/CompanionDiagnostics. 2.2 Recommended Dosage The recommended dosage of HYRNUO is 20 mg orally twice daily with food, until disease progression or unacceptable toxicity [see Clinical Pharmacology (12.3) ] . Swallow tablets whole. Do not cut, crush, or chew tablets. Missed Dose If a dose is missed, take the missed dose as soon as you remember prior to the next scheduled dose. Do not take 2 doses at the same time to make up for the missed dose. Vomited Dose If a dose is vomited, do not take an additional dose. Resume dosing at the next scheduled time. 2.3 Dosage Modifications for Adverse Reactions The recommended dosage reductions for adverse reactions are provided in Table 1. Table 1: Recommended HYRNUO Dosage Reductions for Adverse Reactions Dose Reduction Dosage Modification First 10 mg twice daily Second 10 mg once daily Permanently discontinue HYRNUO in patients who are unable to tolerate 10 mg once daily. The recommended dosage modifications for adverse reactions are provided in Table 2. Table 2: Recommended HYRNUO Dosage Modifications for Adverse Reactions Adverse Reaction Severity Grades based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 5.0. Dosage Modification Diarrhea [see Warnings and Precautions (5.1) ] Intolerable Grade 2 or Grade 3 Interrupt HYRNUO until recovery to Grade ≤1. Resume HYRNUO at the same dose or the next lower dose. For recurrence, resume HYRNUO at the next lower dose. Grade 4 Permanently discontinue HYRNUO. Hepatotoxicity [see Warnings and Precautions (5.2) ] Grade 2, 3 or 4 ALT and/or AST without increased total bilirubin or Grade 3 total bilirubin Interrupt HYRNUO until recovery to Grade ≤1 or baseline. Resume HYRNUO at the next lower dose. ALT or AST ≥ 3× ULN with total bilirubin ≥ 2× ULN or Grade 4 total bilirubin Permanently discontinue HYRNUO. Interstitial lung disease (ILD)/pneumonitis [see Warnings and Precautions (5.3) ] Any Grade Permanently discontinue HYRNUO. Ocular toxicity [see Warnings and Precautions (5.4) ] Grade 2 Interrupt HYRNUO until recovery to Grade ≤1. Resume HYRNUO at the next lower dose. For recurrence, permanently discontinue HYRNUO. Grade 3 or Grade 4 Permanently discontinue HYRNUO. Pancreatic Enzyme Elevation [see Warnings and Precautions (5.5) ] Grade 3 Interrupt HYRNUO until recovery to Grade ≤2 or baseline. Resume HYRNUO at the next lower dose. Grade 4 Permanently discontinue HYRNUO. Other adverse reactions [see Adverse Reactions (6.1) ] Intolerable or recurrent Grade 2 or Grade 3 Interrupt HYRNUO until recovery to Grade ≤1. Resume HYRNUO at the same dose or the next lower dose. For recurrence, resume HYRNUO at the next lower dose. Grade 4 Permanently discontinue HYRNUO. 2.4 Dosage Modifications for Strong CYP3A Inhibitors Avoid concomitant use of strong CYP3A inhibitors. If concomitant use cannot be avoided, reduce HYRNUO dosage as shown in Table 3. After the CYP3A inhibitor has been discontinued for 3 to 5 elimination half-lives, resume the HYRNUO dosage that was used prior to initiating the inhibitor [see Drug Interactions (7.1) ]. Table 3: Recommende

Monitoring

• 5 WARNINGS AND PRECAUTIONS Diarrhea : At the first sign of diarrhea or increased bowel movement frequency, instruct patients to start an antidiarrheal treatment, and to increase their fluid and electrolyte intake.
• Interrupt, reduce the dose, or permanently discontinue HYRNUO based on severity.
• ( 5.1 ) Hepatotoxicity : Monitor liver function tests including ALT, AST, and total bilirubin at baseline prior to administration of HYRNUO, every 2 weeks during the first month, and then monthly thereafter as clinically indicated, with more frequent testing in patients who develop transaminase elevations.
• Interrupt, reduce the dose, or permanently discontinue HYRNUO based on severity.

Interaction Notes

• 7 DRUG INTERACTIONS Strong CYP3A Inhibitors: Avoid concomitant use with strong CYP3A inhibitors.
• If concomitant use cannot be avoided, reduce HYRNUO dosage.
• ( 2.4 , 7.1 ).
• Moderate CYP3A Inhibitors: Monitor patients for increased HYRNUO-associated adverse reactions ( 2.3 , 7.1 ) Strong and Moderate CYP3A Inducers: Avoid concomitant use with strong or moderate CYP3A inducers.