Hernexeos Drug Information
Generic name: ZONGERTINIB
Kinase Inhibitor [EPC]
Uses of 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 . 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. 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. 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.
Dosage & Administration of Hernexeos
| 180 mg | 120 mg |
|---|---|
| 120 mg | 60 mg |
| Permanently discontinue HERNEXEOS in patients who are unable to tolerate 60 mg once daily. | |
Side Effects of Hernexeos
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 . 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) . 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
Nausea 25 0.6 Stomatitis* 21 0 Skin and Subcutaneous Tissue Disorders Rash*
32
Nail disorders* 21 0.6 Pruritus 15 0 General Disorders Fatigue* 26 0.6
Headache 16
Respiratory, Thoracic and Mediastinal Disorders Cough* 23 0 Musculoskeletal and Connective Tissue
Disorders Musculoskeletal pain* 23
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
Leukocytes decreased 35 1.1 Activated partial thromboplastin time increased 23 0 Platelets
decreased 20
Chemistry Alanine aminotransferase increased 41 7 Aspartate aminotransferase increased 35 5 Creatinine
kinase increased 28
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
Bicarbonate decreased 22 0 Magnesium decreased 21 1.1 Potassium decreased 21 1.7
Alkaline phosphate increased 20 1.7
Warnings & Cautions for Hernexeos
Hepatotoxicity
HERNEXEOS can cause severe and life-threatening hepatotoxicity, including drug induced liver injury. In the pooled safety population, based on adverse reaction data, hepatotoxicity occurred in 27% of patients treated with HERNEXEOS. Grade 3 drug induced liver injury occurred in 1.4% and Grade 4 in 0.3% of patients treated with HERNEXEOS. Grade 3 hepatic failure occurred in 0.3% of patients treated with HERNEXEOS. Based on laboratory data, 37% of patients treated with HERNEXEOS experienced increased alanine aminotransferase (ALT), including 4.9% Grade 3 and 1% Grade 4. Increased aspartate aminotransferase (AST) occurred in 31% of patients treated with HERNEXEOS, including 3.8% Grade 3 and 0.7% Grade 4. Increased bilirubin occurred in 20% of patients treated with HERNEXEOS, including 1% Grade 3 and 0.3% Grade 4. HERNEXEOS was interrupted for an adverse reaction of hepatotoxicity in 8% of patients, the dose was reduced in 3.8% and permanently discontinued in 1%. Monitor liver function tests including ALT, AST, and total bilirubin at baseline prior to administration of HERNEXEOS, every 2 weeks during the first 12 weeks, and then monthly thereafter as clinically indicated, with more frequent testing in patients who develop transaminase elevations. Interrupt, reduce the dose, or permanently discontinue HERNEXEOS based on the severity of the adverse reaction.
Left Ventricular Dysfunction
HERNEXEOS can cause severe left ventricular dysfunction. Left ventricular ejection fractions (LVEF) decrease occurred with anti-HER2 therapies, including HERNEXEOS. Treatment with HERNEXEOS has not been studied in patients with a history of clinically significant cardiac disease or LVEF less than 50% prior to initiation of treatment. In the pooled safety population, LVEF decrease occurred in 6% of patients treated with HERNEXEOS, including 1.7% Grade 3. Two patients with Grade 3 LVEF decrease required permanent discontinuation of HERNEXEOS. The median time to onset of decreased LVEF was 12 weeks (range: 2.9 to 63 weeks). Before initiating HERNEXEOS, evaluate LVEF and monitor at regular intervals during treatment and as clinically indicated.
Interrupt, reduce the dose, or permanently discontinue HERNEXEOS based on the severity of the adverse reaction.
Interstitial Lung Disease/Pneumonitis
HERNEXEOS can cause severe and life-threatening interstitial lung disease (ILD)/pneumonitis. In the pooled safety population, ILD/pneumonitis occurred in 2.1% of patients treated with HERNEXEOS. The median time to first onset of ILD/pneumonitis was 13 weeks (range: 1.4 to 65 weeks). One patient was able to resume therapy after resolution of pneumonitis. Two patients required permanent discontinuation and one patient died with unresolved pneumonitis > 30 days after discontinuing HERNEXEOS. Monitor patients for new or worsening symptoms indicative of ILD/pneumonitis (e.g., dyspnea, cough, fever). Interrupt, reduce the dose or permanently discontinue HERNEXEOS based on severity of confirmed ILD/pneumonitis.
Embryo-Fetal Toxicity
Based on findings from animal studies and its mechanism of action, HERNEXEOS can cause fetal harm when administered to a pregnant woman. In an animal reproduction study, oral administration of zongertinib to pregnant rats during the period of organogenesis caused structural abnormalities and alterations to growth at maternal exposures ≥ 19 times the human exposure based on AUC at the recommended dose. Advise pregnant women and females of reproductive potential of the potential risk to a fetus.
Advise females of reproductive potential to use effective contraception during treatment with HERNEXEOS and for 2 weeks after the last dose.
Drug Interactions with Hernexeos
Effects of Other Drugs on
HERNEXEOS Avoid concomitant use of HERNEXEOS with strong CYP3A inducers. If concomitant use cannot be avoided, increase HERNEXEOS dose as recommended. Zongertinib is a CYP3A substrate.
Strong CYP3A4 inducers decrease zongertinib exposure , which may reduce effectiveness of HERNEXEOS.
Effects of
HERNEXEOS on Other Drugs BCRP Substrates Avoid concomitant use of HERNEXEOS with certain BCRP substrates where minimal concentration changes may lead to serious adverse reactions. If coadministration cannot be avoided, monitor for increased adverse reactions and follow recommendations provided in the approved product labeling for the BCRP substrate. For other BCRP substrates, monitor for increased adverse reactions and adjust the dosages of those substrates as clinically appropriate.
Zongertinib is a BCRP inhibitor. HERNEXEOS increases exposure of BCRP substrates , which may increase the risk of adverse reactions related to these substrates.
Pregnancy Safety for Hernexeos
Pregnancy Risk Summary Based on findings from animal studies and its mechanism of action, HERNEXEOS can cause fetal harm when administered to a pregnant woman. There are no available data on the use of HERNEXEOS in pregnant women to inform a drug-associated risk. Oral administration of zongertinib to pregnant rats during the period of organogenesis caused structural abnormalities and alterations to growth at maternal exposures ≥ 19 times the human exposure based on AUC at the recommended dose . Advise pregnant women and females of reproductive potential of the potential risk to a fetus.
In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Animal Data In an embryo-fetal development study, pregnant rats received oral doses of 10, 30, or 60 mg/kg/day of zongertinib during the period of organogenesis (gestation day 7 to 18). Zongertinib caused decreased fetal weights, delayed development of the urinary system, and kidney hydronephrosis at 60 mg/kg/day (approximately 19 times the human exposure based on AUC at the recommended dose). In an embryo-fetal development study in rabbits, there were no adverse embryo-fetal findings in pregnant animals administered oral doses of zongertinib up to 120 mg/kg/day (2.4 times the human exposure based on AUC at the recommended dose) during the period of organogenesis (gestation day 6 to 19). A literature-based assessment of the effects on reproduction demonstrated that mice expressing catalytically inactive HER2 die at mid-gestation due to cardiac dysfunction.
Pediatric Use of Hernexeos
Pediatric Use The safety and effectiveness of HERNEXEOS have not been established in pediatric patients.
Overdosage Information for Hernexeos
Overdose in one patient who ingested 600 mg of HERNEXEOS resulted in nausea and vomiting.
Clinical Studies of Hernexeos
was evaluated in Beamion LUNG-1 (NCT04886804), a single arm, open-label, multi-center, multi-cohort trial. Eligible patients were required to have unresectable or metastatic NSCLC with HER2 (ERBB2) mutations. Patients with stable brain metastases were eligible to enroll.
The study excluded patients who had a history of non-infectious interstitial lung disease/pneumonitis. Patients received HERNEXEOS 120 mg orally once daily until disease progression or unacceptable toxicity. The major efficacy outcome measures were objective response rate (ORR) and duration of response (DOR) by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 as assessed by blinded independent central review (BICR). Previously Untreated Unresectable or Metastatic Non-Squamous NSCLC The efficacy population included 72 patients with unresectable or metastatic, non-squamous NSCLC with HER2 (ERBB2) tyrosine kinase domain (TKD) mutations based on prospective local testing, who had not received prior systemic therapy for advanced disease.
Of those, tumor tissue samples from 60% (43/72) of patients were retrospectively tested using Oncomine™ Dx Target Test (Life Technologies Corporation, Tissue-test). While 86% (37/43) of samples were positive for HER2 (ERBB2) TKD mutations; 14% (6/43) were unevaluable. The baseline demographic and disease characteristics of the efficacy population were: 67 years (range: 35 to 88); 50% female, 47% Asian, 42% White, 1.4% Black or African American; 10% had unknown race data; 6% were of Hispanic or Latino ethnicity; 44% Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 and 56% ECOG PS 1; 65% never smoked; 100% had metastatic disease; and 31% had brain metastases. Efficacy results are summarized in Table 5. Table 5 Efficacy Results for Beamion LUNG-1 in Previously Untreated Non-Squamous NSCLC Efficacy Parameter HERNEXEOS N = 72 Abbreviation: CI = Confidence Interval, +: Ongoing response. 1 Based on Wilson confidence interval. 2 Based on observed duration of response.
Objective Response Rate (ORR), % (95% CI) 1 76 Complete response, % 11 Partial response, % 65 Duration of Response (DOR) N = 55 Range, months 1.4, 18+ DOR ≥ 6 months, 2 % 64 DOR ≥ 12 months, 2 % 44 Previously Treated Unresectable or Metastatic Non-Squamous NSCLC The efficacy population included 71 patients with unresectable or metastatic, non-squamous NSCLC with HER2 (ERBB2) TKD mutations based on prospective local testing. Of those, tumor tissue samples from 52% (37/71) of patients were retrospectively tested using Oncomine™ Dx Target Test (Life Technologies Corporation, Tissue-test). While 84% (31/37) of samples were positive for HER2 (ERBB2) TKD mutations, 2.7% (1/37) did not have HER2 (ERBB2) TKD mutations identified, and 13.5% (5/37) were unevaluable. The baseline demographic and disease characteristics of the efficacy population were: 62 years (range: 30 to 80); 70% female, 55% Asian, 35% White, 0% Black or African American; 10% had unknown race data; 1.4% were of Hispanic or Latino ethnicity; 39% Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 and 61% ECOG PS 1; 65% never smoked; 100% metastatic disease; and 37% with brain metastases.
The median number of prior therapies was 1 (range: 1 to 10); 100% of patients had prior platinum therapy and 78% had prior treatment with anti-PD-1/PD-L1 antibody. No patient had received previous treatment with a HER2-targeted tyrosine kinase inhibitor (TKI) or HER2-targeted antibody-drug conjugate (ADC). Efficacy results are summarized in Table 6. Table 6 Efficacy Results for Beamion LUNG-1 in Previously Treated Non-Squamous NSCLC Efficacy Parameter HERNEXEOS N = 71 Abbreviation: CI = Confidence Interval, +: Ongoing response. 1 Based on Wilson confidence interval. 2 Based on observed duration of response. Objective Response Rate (ORR), % (95% CI) 1 75 Complete response, % 6 Partial response, % 69 Duration of Response (DOR) N = 53 Range, months 1.3+, 15+ DOR ≥ 6 months, 2 % 58 Among the 71 patients, 5 patients had measurable CNS metastases at baseline as assessed by BICR and had not received radiation therapy to the brain within 2 months prior to treatment with HERNEXEOS. Based on Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) criteria per BICR, responses were observed in 3 patients.
HERNEXEOS was also evaluated in 34 patients with unresectable or metastatic HER2 (ERBB2) TKD mutation-positive non-squamous NSCLC who had received previous treatment with platinum-based chemotherapy and a HER2-targeted ADC. Eligibility criteria were otherwise similar to the efficacy population described above. The median age was 58 years (range: 31 to 85); 65% female, 35% Asian, 50% White, 0% Black or African American; 15% had unknown race data; and 2.9% were of Hispanic or Latino ethnicity. Baseline ECOG performance status was 0 (21%) or 1 (79%); 65% never smoked; 100% of patients had metastatic disease and 74% had brain metastases.
The median number of prior therapies was 3 (range: 1 to 8); 100% of patients had prior platinum therapy and 77% had prior treatment with anti-PD-1/PD-L1 antibody; 2.9% of patients had received previous treatment with a HER2-targeted TKI. Confirmed ORR by RECIST v1.1 based on BICR was 44% (95% CI 29, 61), with 2.9% of patients having a complete response. Median DOR was 5.4 months (95% CI 2.8, not estimable), and 27% of responders had an observed DOR ≥ 6 months.
Drug information sourced from the FDA. This content is for informational purposes only and does not constitute medical advice. Consult a healthcare professional before making any medication decisions.
Ready to save on Hernexeos?
Compare prescription prices at over 70,000 pharmacies and start saving today—no enrollment required.
Compare Hernexeos Prices