HYRNUO, NOW APPROVED FOR FIRST LINE
FOR HER2-MUTATED NSCLC.

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-authorized test.

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.

*HER2 is also referred to as ERBB2.

ERBB2 (erb-b2 receptor tyrosine kinase 2).

See resources

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-authorized test.

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.

IN THE 1L SETTING, HYRNUO HAS THE POWER OF DELIVERING A DURABLE RESPONSE1

TREATMENT NAIVE PATIENTS WITH HER2 (ERBB2) TKD-
ACTIVATING MUTATIONS

75 percent displayed inside a circular progress icon

75% OF PATIENTS TREATED WITH HYRNUO ACHIEVED AN
OBJECTIVE RESPONSE1†‡

(95% CI: 64, 85; N=69)
CR: 6% (n=4), PR: 70% (n=48)

Calendar icon displaying 15.1 months

1.5 to 21.6+ MONTHS†‖

(N=52)

  • At ≥6 months, 73% continued to respond to treatment§ 
  • At ≥12 months, 38% continued to respond to treatment§

†Major efficacy outcomes were confirmed ORR and DOR as assessed by BICR using RECIST v1.1.1  

‡ORR (95% CI) calculated using the Clopper-Pearson method.1

§Observed proportion of responding patients with DOR beyond landmark time.1

∥The + symbol refers to an ongoing response.

HYRNUO WAS EVALUATED IN A MULTICOHORT STUDY OF PATIENTS WITH HER2-MUTATED NSCLC1

SOHO-01 was a global, open-label, single-arm, multicohort Phase I/II trial
studying HYRNUO in patients with HER2 (ERBB2) TKD-activating mutations in
locally advanced or metastatic non-squamous NSCLC.1,2

  • The efficacy population presented here includes treatment naive patients (Group 
    F, N=69)
  • Safety was evaluated in 191 patients (Groups D, E, F)1
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    Select inclusion/exclusion criteria

    Select Inclusion Criteria1,2

    • Locally advanced or metastatic non-squamous NSCLC with HER2 (ERBB2) TKD-activating mutations
    • ≥18 years
    • ECOG PS 0 or 1
    • Patients with treated, stable, and asymptomatic brain metastases were 
      eligible

    Select Exclusion Criteria1

    • Patients with symptomatic CNS metastasis, clinically significant
cardiac 
      disease, and history of steroid-dependent interstitial lung disease (ILD)/
      pneumonitis

    HYRNUO 20 mg BID1

    Efficacy and Safety Population

    Eligible patients included:

    • Group F: Treatment naive (N=69)
    • Group D: Pretreated, received prior systemic therapy, but naive to HER2-targeted therapy (N=70)
    • Group E: Pretreated, received prior systemic therapy, including HER2-targeting ADCs (N=52)
      • Safety was evaluated in 191 patients with locally advanced or metastatic non-squamous NSCLC harboring HER2-activating mutations across Groups D, E, and F

    Endpoints1,2

    • Primary:
      • Overall response rate (ORR)
      • Safety profile
    • Secondary:
      • Duration of response (DoR)
    Key patient characteristics

    Treatment naive patients (Group F, N=69)1

    • 61% of patients were female
    • 78% were never-smokers, 22% were former-smokers
    • The median age was 66 years (range 31 to 82)
    • 73% of patients had ECOG PS 1, 26% had ECOG PS 0, and 1.4% had ECOG 
      PS 2
    • 84% of patients had Stage IV NSCLC
    • 12% of patients had stable brain metastases

    ADVERSE REACTIONS WERE ASSESSED IN A POOLED POPULATION OF 287 PATIENTS

    The pooled safety population reflects exposure to HYRNUO at 20 mg orally twice
    daily in 287 patients with locally advanced or metastatic NSCLC harboring HER2
    activating and/or other mutations from the SOHO-1 study.1

    Of the 287 patients who received 20 mg of HYRNUO orally, twice daily1:

    • 61% were exposed for >6 months
    • 37% were exposed for >12 months

    Most common (>20%)
    adverse reactions1

    Diarrhea

    Rash

    Paronychia

    Nausea

    Vomiting

    Stomatitis

    Most common (≥2%) Grade 3 or 4
    laboratory abnormalities1

    Decreased potassium

    Increased lipase

    Decreased phosphate

    Decreased lymphocyte count

    Decreased sodium

    Increased amylase

    Decreased hemoglobin

    Increased ALT

    Increased AST

    Decreased calcium

    AMONG ADVERSE REACTIONS OCCURRING IN ≥15% OF
    PATIENTS, NO GRADE 4 EVENTS WERE REPORTED1

    The established safety profile of HYRNUO is based on data from 191 patients
    with locally advanced or metastatic non-squamous NSCLC harboring HER2
    (ERBB2) TKD-activating mutations in SOHO-01 (Groups D, E, and F).1

    • Diarrhea was the most common adverse reaction and was reported in 90% 
      of patients
      • There were no treatment discontinuations due to diarrhea
    • Serious adverse reactions occurred in 33% of patients
      • Most common (≥2%): diarrhea (3.7%), dyspnea (3.1%), vomiting (3.7%), pneumonia (2.6%), and pleural effusion (2.1%). A fatal adverse reaction of cerebral infarction occurred in one patient (0.5%)
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      See full table for adverse reactions in ≥15% of patients in SOHO-01 (N=191)1

      Adverse reactions in ≥15% of patients in SOHO-01 (N=191)1*

      Of the Adverse Reactions below, no Grade 4 were reported.

      Adverse Reactions*All Grades (%)Grade 3 or 4† (%)
      Gastrointestinal disorders
      Diarrhea‡9014
      Stomatitis‡371
      Nausea222.1
      Vomiting‡194.2
      Skin and subcutaneous tissue disorders
      Rash‡761.6
      Paronychia‡361
      Dry skin‡180
      Pruritus161
      Investigations
      Weight decreased220.5
      Metabolism and nutrition disorders
      Decreased appetite192.6
      Musculoskeletal and connective tissue disorders
      Musculoskeletal pain‡180
      General disorders and administration site conditions
      Fatigue‡172.6
      Eye disorders
      Ocular toxicity‡160.5

      *Graded per NCI CTCAE version 5.

      †No Grade 4 were reported.

      ‡Grouped term.

      LOW DISCONTINUATION RATES DUE TO ADVERSE
      REACTIONS

      Majority of patients continued treatment without dose reductions or
      interruptions

      68% with sample size N equals 130 out of 191

      WERE TREATED WITH NO DOSE REDUCTIONS1

      Dose reductions due to adverse reactions occurred in 32% of patients who received HYRNUO.

      Adverse reactions leading to dose reductions in >2% of patients: 

      diarrhea, hepatotoxicity, rash, potassium decrease, stomatitis, vomiting, decreased appetite.

      51% with sample size N equals 94 out of 191

      WERE TREATED WITH NO TREATMENT INTERRUPTIONS1

      Dose interruptions due to adverse reactions occurred in 49% of patients who received HYRNUO.

      Adverse reactions leading to dose interruptions in >2% of patients:

      diarrhea, potassium decreased, hepatotoxicity, nausea, vomiting, rash, pneumonia, paronychia, decreased appetite, pruritus, acute kidney injury, stomatitis.

      4.2% with sample size N equals 8 out of 191

      DISCONTINUED TREATMENT DUE TO ADVERSE REACTIONS1

      Permanent discontinuation of HYRNUO due to an adverse reaction occurred in 4.2% of patients.

      Adverse reactions leading to discontinuation:

      corneal epithelial microcysts, hepatic function abnormal, blood alkaline phosphatase increased, electrocardiogram QT prolonged, pain in extremity, renal failure, dyspnea (1 patient each).

      IN THE SAFETY POPULATION, DIARRHEA RESULTED IN NO TREATMENT DISCONTINUATIONS

      • The most common adverse reaction was diarrhea (90%). This includes diarrhea 
        and enterocolitis1
      • No Grade 4 diarrhea was reported1
      • Adverse reactions such as diarrhea are often linked to certain TKIs and have 
        established mitigation approaches3

      RECOMMENDATIONS FOR DIARRHEA MANAGEMENT1:

      At first sign of diarrhea or increased bowel movement frequency:

      • Advise patients to start an antidiarrheal treatment such as loperamide
      • Instruct patients to increase fluid and electrolyte intake

      Based on the severity of diarrhea, interrupt, reduce the dose, or permanently
      discontinue HYRNUO dosage.

      For intolerable Grade 2 or Grade 3 diarrhea:

      • 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

      For Grade 4 diarrhea, permanently discontinue HYRNUO.

      RECOMMENDED DOSING

      Recommended dosing instructions for HYRNUO

      FIXED ORAL DOSING WITH HYRNUO1

      • No weight-based dosing is required
      • The recommended dose of HYRNUO is 20 mg (two 10 mg tablets) taken orally twice daily with food, for a total daily dose of 40 mg, until disease progression or unacceptable toxicity
        • Swallow tablets whole. Do not cut, crush, or chew tablets
      • Missed dose: Patients must take the missed dose as soon as they 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

      Dose modification options enable treatment
      adjustments when needed, and can help maintain
      uninterrupted treatment with HYRNUO.1

      • First recommended dose reduction: 10 mg twice daily
      • Second recommended dose reduction: 10 mg once daily
      • Permanently discontinue HYRNUO in patients who are unable to tolerate 10 mg once daily

      EXPLORE HELPFUL MATERIALS

      FOR YOUR PATIENTS

      Patient Brochure
      Managing Side Effects
      Patient Support Program Overview

      FOR YOUR PRACTICE

      Product Fact Sheet
      Patient Services Request Form
      Sample Letter of Medical Necessity
      AE Management Tool
      HYRNUO Access Guide
      Sample Letter of Appeal
      HCP Core Brochure

      APPROVED IN-OFFICE DISPENSING PHARMACIES CAN REQUEST A PATIENT SUPPORT KIT VIA THE REQUEST-A-SPECIALIST PAGE.

      Request a Specialist

      BAYER OFFERS PERSONALIZED SUPPORT FOR YOUR HYRNUO PATIENTS

      PERSONALIZED SUPPORT THROUGHOUT YOUR PATIENT’S TREATMENT JOURNEY

      Once you've made the decision to prescribe HYRNUO, you can do so through our dedicated specialty pharmacy, Onco360TM. Onco360TM provides oncology-focused care to your patients.

      Icon of 3 patients, one in purple and two in navy blue

      FOR ALL PATIENTS

      All patients NEW to HYRNUO are eligible for a 1-month free trial to help them start HYRNUO at no cost*

      • One-month supply of HYRNUO allows HCPs and patients to determine if it is the right treatment option at no cost to payer or patient. Enroll through Onco360™
      Insurance card icon for copay program

      FOR PATIENTS WITH COMMERCIAL INSURANCE

      Co-pay program

      Eligible patients may pay as little as $0 for HYRNUO†

      • Eligible patients will automatically be re-enrolled every January
      • Benefit limits apply
      Enroll your patient
      Hand holding heart with cross sign icon

      FOR PATIENTS WITH MEDICARE

      Patients may qualify for help to pay for out-of-pocket costs for HYRNUO

      *Participation in the HYRNUO Free Trial Program is limited to 1 time only per product (patients currently using HYRNUO are not eligible for a Free Trial of their current product). The Free Trial Program includes 1 month supply. The Free Trial Program for HYRNUO is available to patients 18 years of age and older. Bayer reserves the right to rescind, revoke, or amend this offer without notice at any time.

      †Patients are eligible if they are commercially insured and may pay as little as $0 per month. Benefit limitations apply. Patients who are enrolled in any type of government insurance or reimbursement programs are not eligible. As a condition precedent of the co-payment support provided under this program, eg, Co-Pay refunds, participating patients and pharmacies are obligated to inform insurance companies and third-party payers of any benefits they receive and the value of this program, and may not participate if this program is prohibited by or conflicts with their private insurance policy, as required by contract or otherwise. Void where prohibited by law, taxed, or restricted. Patients enrolled in the Bayer US Patient Assistance Foundation are not eligible. Bayer may determine eligibility, monitor participation, equitably distribute product and modify or discontinue any aspect of the HYRNUO $0 Co-Pay Program at any time, including but not limited to this commercial Co-Pay assistance program.

      Bayer US patient assistance foundation logo

      IF YOUR PATIENTS CANNOT AFFORD THEIR PRESCRIPTION MEDICATION, BAYER MAY BE ABLE TO HELP

      The Bayer US Patient Assistance Foundation is a charitable organization that helps eligible patients get their Bayer prescription medicine at no cost. Please have your patient contact the program at 1-866-2BUSPAF (228-7723) Monday–Friday, 9:00 AM–6:00 PM EST, or visit the foundation website at www.patientassistance.bayer.us to see if they might qualify for assistance.

      Important Safety Information

      Warnings & Precautions

      Diarrhea

      HYRNUO can cause severe diarrhea that can lead to dehydration and electrolyte imbalances.

      In the pooled safety population, diarrhea was reported in 89% of patients who received HYRNUO including 16% Grade 3. The median time to first onset of any grade diarrhea was four days. Dosage interruptions occurred in 15% of patients, and dose reductions occurred in 14% of patients.

      At the first sign of diarrhea or increased bowel movement frequency, instruct patients to start an antidiarrheal treatment (e.g., loperamide), and to increase their fluid and electrolyte intake. Interrupt, reduce the dose, or permanently discontinue HYRNUO based on severity.

      Hepatotoxicity

      HYRNUO can cause severe hepatotoxicity characterized by elevations of liver function tests.

      In the pooled safety population, based on adverse reaction data, hepatotoxicity occurred in 29% of patients treated with HYRNUO, including 3.1% Grade 3 and 0.3% Grade 4.

      Based on laboratory data, 41% of patients treated with HYRNUO experienced increased alanine aminotransferase (ALT), including 2.5% Grade 3 and 0.4% Grade 4. Increased aspartate aminotransferase (AST) occurred in 44% of patients treated with HYRNUO, including 2.5% Grade 3. Increased bilirubin occurred in 15% of patients treated with HYRNUO. The median time to first onset of AST or ALT elevation was 1.4 (range: 0.2 to 24.1) months.

      HYRNUO was interrupted for an adverse reaction of hepatotoxicity in 4.2% of patients, the dose was reduced in 4.9%, and permanently discontinued in 0.3%.

      Monitor liver function tests including ALT, AST, and total bilirubin at baseline prior to the first administration of HYRNUO, every 2 weeks for 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.

      Interstitial Lung Disease/Pneumonitis

      HYRNUO can cause severe interstitial lung disease (ILD)/pneumonitis.

      In the pooled safety population, ILD/pneumonitis occurred in four patients (1.4%) treated with HYRNUO, including 0.3% Grade 3. One patient required interruption of HYRNUO.

      Monitor patients for new or worsening symptoms indicative of ILD/pneumonitis (e.g., dyspnea, cough, fever). Discontinue HYRNUO upon confirmation of ILD/pneumonitis.

      Left Ventricular Dysfunction

      HYRNUO can cause severe left ventricular dysfunction. Left ventricular ejection fraction (LVEF) decrease has occurred with anti-HER2 therapies, including HYRNUO.

      Treatment with HYRNUO 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 one patient (0.3%) treated with HYRNUO. This Grade 3 LVEF decrease required permanent discontinuation of HYRNUO, and the event recovered.

      Evaluate LVEF prior to initiation of HYRNUO and monitor at regular intervals during treatment and as clinically indicated. Interrupt, reduce the dose, or permanently discontinue HYRNUO based on severity.

      Ocular Toxicity

      HYRNUO can cause ocular toxicity.

      In the pooled safety population, ocular toxicity occurred in 17% of patients treated with HYRNUO, including 11% Grade 1, 4.9% Grade 2, and 0.3% Grade 3 (one case of corneal epithelial microcysts with temporary unilateral blindness).

      Promptly refer patients presenting with new or worsening eye symptoms to an ophthalmologist. Interrupt, reduce the dose, or permanently discontinue HYRNUO based on severity.

      Pancreatic Enzyme Elevation

      HYRNUO can cause elevations of amylase and lipase levels.

      In the pooled safety population, based on laboratory data, increased amylase occurred in 39% of patients treated with HYRNUO, including 3.9% Grade 3 and 0.7% Grade 4. Increased lipase occurred in 48% of patients treated with HYRNUO, including 13% Grade 3 and 1.1% Grade 4. Four patients (1.4%) required interruption of HYRNUO due to increased lipase and three (1%) required interruption of HYRNUO due to increased amylase. One patient (0.3%) required dose reduction of HYRNUO due to increased amylase. The median time to onset of increased amylase/lipase was 0.7 months (range: 0.2 to 20.4 months).

      Monitor amylase and lipase regularly during treatment with HYRNUO. Interrupt, reduce the dose, or permanently discontinue HYRNUO based on severity.

      Embryo-Fetal Toxicity

      Based on findings from animal studies and its mechanism of action, HYRNUO can cause fetal harm when administered to a pregnant woman. In embryo-fetal development studies, oral administration of sevabertinib to pregnant rats during the period of organogenesis resulted in alterations to growth at maternal exposures ≥0.18 times the human exposure based on area under the curve (AUC) at the clinical dose of 20 mg twice daily. Animal studies with disrupted or depleted HER2/EGFR and in vitro assays have demonstrated that inhibition of HER2 and/or EGFR results in structural abnormalities, alteration to growth, and embryo-fetal and infant mortality.

      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 HYRNUO and for 1 week after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with HYRNUO and for 1 week after the last dose.

      Adverse Reactions

      In SOHO-01, serious adverse reactions occurred in 33% of patients who received HYRNUO. Serious adverse reactions in ≥2% of patients were diarrhea (3.7%), dyspnea (3.1%), vomiting (3.7%), pneumonia (2.6%), and pleural effusion (2.1%). A fatal adverse reaction of cerebral infarction occurred in one patient (0.5%) who received HYRNUO.

      The most common adverse reactions (>20%) in patients who received HYRNUO were diarrhea (90%), rash (76%), stomatitis (37%), paronychia (36%), nausea (22%) and weight decreased (22%).

      The most common (≥2%) Grade 3 or 4 laboratory abnormalities were lipase increased (18%), potassium decreased (18%), phosphate decreased (13%), lymphocyte count decreased (4.6%), sodium decreased (5%), amylase increased (5%), hemoglobin decreased (3.7%), ALT increased (3.2%), and increased AST (2.6%). Laboratory abnormalities in <20% of patients who received HYRNUO include bilirubin increased (19%; all were Grades 1 and 2), platelet count decreased, and neutrophil count decreased (16% each).

      Clinically relevant adverse reactions in <15% of patients who received HYRNUO included abdominal pain (14%), cardiac arrhythmia (10%; including arrhythmia, atrial fibrillation, atrial tachycardia, atrioventricular block complete, atrioventricular block first degree, electrocardiogram QT prolonged, sinus arrhythmia, sinus bradycardia, sinus tachycardia, supraventricular extrasystoles, supraventricular tachycardia, tachycardia, and ventricular extrasystoles), and alopecia (7%).

      Drug Interactions

      Effects of Other Drugs on HYRNUO – Sevabertinib is a CYP3A substrate. Concomitant use with a strong or moderate CYP3A inhibitor may increase sevabertinib plasma concentrations, which may increase the risk of HYRNUO-associated adverse reactions. Monitor patients for increased HYRNUO-associated adverse reactions with moderate CYP3A inhibitors. Avoid concomitant use of HYRNUO with strong CYP3A inhibitors. If concomitant use cannot be avoided, reduce HYRNUO dose.

      Concomitant use with a strong or moderate CYP3A inducer may decrease sevabertinib plasma concentrations, which may decrease the effectiveness of HYRNUO. Avoid concomitant use of HYRNUO with strong or moderate CYP3A inducers.

      Effects of HYRNUO on Other Drugs – Sevabertinib is a weak to moderate CYP3A inhibitor. Sevabertinib increases exposure of CYP3A substrates, which may increase the risk of adverse reactions related to these substrates. Avoid concomitant use of HYRNUO with CYP3A substrates where minimal increases in the concentration may lead to serious adverse reactions unless otherwise recommended in the Prescribing Information of the CYP3A substrate.

      Sevabertinib is a P-gp inhibitor. Sevabertinib increases exposure of P-gp substrates, which may increase the risk of adverse reactions related to these substrates. Refer to the Prescribing Information for P-gp substrates where minimal increases in the concentration may lead to serious adverse reactions.

      Sevabertinib is an inhibitor of CYP1A1 in vitro. Sevabertinib may increase exposure of CYP1A1 substrates, which may increase the risk of adverse reactions related to these substrates. Refer to the Prescribing Information of CYP1A1 substrates.

      You are encouraged to report side effects or quality complaints of products to the FDA by visiting www.fda.gov/medwatch or calling 1-800-FDA-1088.

      Please see full Prescribing Information. 

      Indication

      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-authorized test.

      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.

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        Abbreviations

        1L=first-line; ALT=alanine aminotransferase; AST=aspartate aminotransferase; BICR=blinded independent central review; BID=twice a day; Cl=confidence interval; CNS=central nervous system; CR=complete response; DoR=duration of response; ECOG PS=Eastern Cooperative Oncology Group Performance Status; ERBB2=erythroblastic oncogene B; HER2=human epidermal growth factor receptor 2; ILD=interstitial lung disease; NE=not estimable; NSCLC=non–small cell lung cancer; ORR=objective response rate; PR=partial response; QT=represents the duration of time taken from the onset of ventricular depolarization to the end of ventricular repolarization; RECIST=Response Evaluation Criteria in Solid Tumors; TKD=tyrosine kinase domain; TKI=tyrosine kinase inhibitor.

        References

        1. HYRNUO (sevabertinib). Prescribing Information. 2026.

        2. ClinicalTrials.gov. NCT05099172. Available at: https://clinicaltrials.gov/study/NCT05099172. Accessed May 20, 2026.

        3. Yin X, et al. Clin Transl Sci. 2021;14(3):919-933.

        Site last modified 09/2026

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