HERNEXEOS

HERNEXEOS is an FDA-registered drug product whose active ingredient is ZONGERTINIB. It is labelled by Boehringer Ingelheim Pharmaceuticals, Inc. taken by oral and marketed as a human prescription drug product. Identifiers on file: NDC 0597-9257, application NDA219042, label effective 20260813. This page reproduces the FDA-approved label text so you can check what a product is, who makes it and how it is supplied before discussing it with a pharmacist or prescriber.

Across FDA labelling, products containing ZONGERTINIB are most often described in connection with: treatment adult, unresectable metastatic, non-squamous non-small, cell lung, cancer nsclc, erbb tyrosine, kinase domain, activating mutations. Wording differs between labels, and the full indications section on this page takes precedence when it is present.

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) ] . This indication is approved under accelerated approval based on objective response rate and duration of response [see Clinical Studies (14) ] . Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. HERNEXEOS is a kinase inhibitor 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. ( 1 ) This indication is approved under accelerated approval based on objective response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. ( 1 )

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 or plasma specimens [see Clinical Studies (14) ] . If no mutation is detected in a plasma specimen, test tumor tissue. 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.

4 CONTRAINDICATIONS None. None. ( 4 )

6 ADVERSE REACTIONS The following adverse reactions are discussed in greater detail in other sections of the labeling: Hepatotoxicity [see Warnings and Precautions (5.1) ] Left Ventricular Dysfunction [see Warnings and Precautions (5.2) ] Interstitial Lung Disease/Pneumonitis [see Warnings and Precautions (5.3) ] Most common adverse reactions (≥ 20%) are diarrhea, rash, hepatotoxicity, fatigue, nausea, musculoskeletal pain, and upper respiratory tract infection. ( 6.1 ) The most common (≥ 2%) Grade 3 or 4 laboratory abnormalities were decreased lymphocytes, increased alanine aminotransferase, increased aspartate aminotransferase, increased gamma glutamyl transferase, decreased potassium, and decreased neutrophils. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Boehringer Ingelheim Pharmaceuticals, Inc. at 1-800-542-6257 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. The pooled safety population described in WARNINGS AND PRECAUTIONS reflects exposure to HERNEXEOS in 292 patients with unresectable or metastatic non-squamous NSCLC with HER2 (ERBB2) mutations who received HERNEXEOS as a single agent at 120 mg orally once daily until disease progression or unacceptable toxicity in Beamion LUNG-1 [see Clinical Studies (14) ] . Among 292 patients who received HERNEXEOS, 59% of patients were exposed for 6 months or longer and 28% were exposed for greater than one year. In this pooled safety population, the most common (≥ 20%) adverse reactions were diarrhea (54%), rash (28%), hepatotoxicity (27%), fatigue (25%), nausea (23%), musculoskeletal pain (21%), and upper respiratory tract infection (20%). The most common (≥ 2%) Grade 3 or 4 laboratory abnormalities were decreased lymphocytes (10%), increased alanine aminotransferase (6%), increased aspartate aminotransferase (4.5%), increased gamma glutamyl transferase (2.8%), decreased potassium (2.4%), and decreased neutrophils (2.4%). Beamion LUNG-1 The safety of HERNEXEOS was evaluated in Beamion LUNG-1 in 177 patients with unresectable or metastatic non-squamous NSCLC with HER2 tyrosine kinase domain (TKD) mutations; 72 patients had not received prior treatment; 105 patients had received prior platinum-based chemotherapy, and out of those patients, 34 patients had received prior treatment with a HER2-directed antibody drug conjugate (ADC) [see Clinical Studies (14) ] . Patients received HERNEXEOS as a single agent at 120 mg once daily until disease progression or unacceptable toxicity. Among patients who received HERNEXEOS, 74% were exposed for 6 months or longer and 42% were exposed for greater than one year. The median age of patients who received HERNEXEOS was 63 years (range 30 to 88), 61% were female, 41% White, 48% Asian, and 0.6% Black or African American; 11% had unknown race data; 3.4% were of Hispanic or Latino ethnicity; and 38% had an Eastern Cooperative Oncology Group (ECOG) performance score of 0 and 62% had an ECOG performance score of 1. Serious adverse reactions occurred in 36% of patients receiving HERNEXEOS. Serious adverse reactions in ≥ 2% of patients included pulmonary embolism (4%), dyspnea (3.4%), pneumonia (2.8%), hepatotoxicity, pleural effusion, and pericardial effusion (2.3%). Fatal adverse reactions occurred in one patient (0.6%) who received HERNEXEOS, due to pneumonia. Permanent discontinuation of HERNEXEOS due to an adverse reaction occurred in 6% of patients. Adverse reactions which resulted in permanent discontinuation of HERNEXEOS were hepatotoxicity, decreased ejection fraction, anemia, increased blood alkaline phosphatase, diarrhea, dyspnea, increased gamma-glutamyl transferase, hemoptysis, pericardial effusion, pneumonitis, and pyrexia. Dosage interruption of HERNEXEOS due to an adverse reaction occurred in 34% of patients. Adverse reactions which required dosage interruption in ≥ 2% of patients were hepatotoxicity, decreased ejection fraction, diarrhea, COVID-19, rash, and vomiting. Dose reductions of HERNEXEOS due to adverse reactions occurred in 9% of patients. Adverse reactions which required dose reductions in ≥ 1% of patients were hepatotoxicity, decreased ejection fraction, and diarrhea. Tables 3 and 4 summarize adverse reactions and laboratory abnormalities observed in Beamion LUNG-1. Table 3 Adverse Reactions (≥ 15%) in Patients with Non-Squamous NSCLC with HER2 TKD Mutations Who Received HERNEXEOS in Beamion LUNG-1 Adverse Reaction HERNEXEOS N = 177 All Grades 1 % Grade 3 or 4 % Events were graded using NCI CTCAE version 5.0. 1 No Grade 4 or Grade 5 adverse reactions occurred. *Grouped term. Gastrointestinal Disorders Diarrhea* 56 2.8 Nausea 25 0.6 Stomatitis* 21 0 Skin and Subcutaneous Tissue Disorders Rash* 32 0.6 Nail disorders* 21 0.6 Pruritus 15 0 General Disorders Fatigue* 26 0.6 Headache 16 0.6 Respiratory, Thoracic and Mediastinal Disorders Cough* 23 0 Musculoskeletal and Connective Tissue Disorders Musculoskeletal pain* 23 2.3 Infections and Infestations Upper respiratory tract infections* 23 0 Clinically relevant adverse reactions in < 15% of patients who received HERNEXEOS included vomiting, dyspnea, dysgeusia, and dry skin. Table 4 Select Laboratory Abnormalities (≥ 20%) in Patients with Non-Squamous NSCLC with HER2 TKD Mutations Who Received HERNEXEOS in Beamion LUNG-1 Laboratory Parameter HERNEXEOS N = 177 All Grades 1 % Grade 3 or 4 % Events were graded using NCI CTCAE version 5.0. 1 No Grade 5 adverse reactions occurred. Hematology Lymphocytes decreased 56 12 Hemoglobin decreased 37 1.1 Leukocytes decreased 35 1.1 Activated partial thromboplastin time increased 23 0 Platelets decreased 20 1.1 Chemistry Alanine aminotransferase increased 41 7 Aspartate aminotransferase increased 35 5 Creatinine kinase increased 28 1.7 Calcium decreased 28 0.6 Albumin decreased 26 0 Bilirubin increased 25 1.1 Lipase increased 25 0 Triglycerides increased 25 0 Sodium decreased 22 0.6 Bicarbonate decreased 22 0 Magnesium decreased 21 1.1 Potassium decreased 21 1.7 Alkaline phosphatase increased 20 1.7

5 FDA recall record(s) match this product name or manufacturer. A match means the firm or product name appears in the enforcement report; confirm lot numbers and dates against the official FDA notice before acting.

What is HERNEXEOS used for?
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) ] . This indication is approved under accelerated approval based on objective …

Who makes HERNEXEOS?
Boehringer Ingelheim Pharmaceuticals, Inc. is the labeler of record for HERNEXEOS.

What form does HERNEXEOS come in?
administered by oral. Strengths and pack sizes vary by label, so compare the NDC on your pack with the identifier listed on this page.

Is HERNEXEOS prescription or over-the-counter?
The FDA label for this product is recorded as human prescription drug. Marketing status can differ between strengths and countries, so check the dispensing rules where you live.

Has HERNEXEOS been recalled?
5 FDA recall record(s) match this product name or manufacturer. Review the recall and safety notices section on this page and confirm lot numbers against the official FDA enforcement report.

Where does this information come from?
All content is reproduced from FDA Structured Product Labelling data via openFDA. It is provided for identification and reference only and is not medical advice.