These Highlights Do Not Include All The Information Needed To Use Hernexeos Safely And Effectively. See Full Prescribing Information For Hernexeos.

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.

Storage and Handling

Store at 20°C to 25°C (68°F to 77°F), excursions permitted to 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature].

Store in the original container to protect from moisture. Keep the bottle tightly closed. Do not remove the desiccants. Once opened, use within 3 months. Discard any unused tablets 3 months after opening the bottle.

Overdose in one patient who ingested 600 mg of HERNEXEOS resulted in nausea and vomiting.

HERNEXEOS tablets for oral administration contain zongertinib, a kinase inhibitor. The chemical name of zongertinib is 2-Propenamide, N-[1-[8-[[3-methyl-4-[(1-methyl-1H-benzimidazol-5-yl)oxy]phenyl] amino]pyrimido[5,4-d]pyrimidin-2-yl]-4-piperidinyl]-. Its molecular formula is C₂₉H₂₉N₉O₂ and the molecular weight is 535.6. The structural formula is:

Zongertinib is a yellow to dark yellow or orange solid. Zongertinib is slightly soluble at pH 1.2, and practically insoluble at pHs 3.6, 4.5, 5.4 and 6.8.

Each film-coated tablet of HERNEXEOS contains 60 mg of zongertinib and the following inactive ingredients: colloidal silicon dioxide, croscarmellose sodium, hypromellose acetate succinate, mannitol, microcrystalline cellulose, and sodium stearyl fumarate. In addition, the film-coating contains the following inactive ingredients: ferric oxide (yellow), glycerol mono and dicaprylocaprate, polyvinyl alcohol, sodium lauryl sulfate, talc, and titanium dioxide.

The safety and effectiveness of HERNEXEOS have not been established in pediatric patients.

Of the 292 patients with non-squamous NSCLC with HER2 (ERBB2) mutations who received HERNEXEOS in clinical studies, 47% were 65 years of age and older and 13% were 75 years and older. No overall differences in safety or effectiveness of HERNEXEOS were observed between older and younger adult patients.

HERNEXEOS can cause severe and life-threatening hepatotoxicity, including drug induced liver injury. In the pooled safety population [see Adverse Reactions (6.1)], 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 [see Dosage and Administration (2.3)].

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).

None.

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)]

• Strong CYP3A Inducers: Avoid concomitant use with strong CYP3A inducers. If concomitant use cannot be avoided, increase HERNEXEOS dose. (7.1)
• BCRP Substrates: Avoid concomitant use with certain BCRP substrates where minimal concentration increase may lead to serious adverse reactions and consider alternative therapies. If concomitant use cannot be avoided, monitor patients closely for adverse reactions and follow recommendations provided in the BCRP substrate approved product labeling. For other BCRP substrates, monitor for increased adverse reactions and adjust the dosages of those substrates as clinically appropriate. (7.2)

The exposure-response relationship and time-course of pharmacodynamic response of zongertinib have not been fully characterized.

Zongertinib pharmacokinetics were observed at steady state in patients with advanced or metastatic solid tumors with HER2 aberrations at the approved recommended dosage and are presented as geometric mean (CV%), unless otherwise specified.

Zongertinib maximum concentration (C_max,ss) is 3.0 (37%) µmol/L and the total systemic exposure (AUC) is 34 (34%) µmol*h/L following HERNEXEOS 120 mg orally daily. Zongertinib C_max and AUC increase in an approximately dose proportional manner across the dose range of 60 mg (0.5 times the approved recommended dosage) to 360 mg (3 times the approved recommended dosage). Zongertinib accumulation is approximately 1.5-fold for AUC and 1.3-fold for C_max at the approved recommended dosage. Steady state is achieved within 2.5 days.

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.

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.

Zongertinib is a kinase inhibitor of human epidermal growth factor receptor 2 (HER2). In vitro, zongertinib inhibited phosphorylation of HER2, downstream signaling of HER2 (phosphorylation of ERK), and proliferation of lung cancer cells harboring HER2 tyrosine kinase domain activating mutations. In vivo, zongertinib demonstrated anti-tumor activity in mouse xenograft models of NSCLC harboring HER2 tyrosine kinase domain activating mutations.

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 [see Use in Specific Populations (8.1, 8.3)].

• 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)

60 mg tablets: yellow, oval, biconvex, film-coated tablets, debossed with "L6" on one side and the Boehringer Ingelheim company symbol on the other side. Each tablet contains 60 mg of zongertinib.

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%).

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 [see Adverse Reactions (6.1)], 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 [see Dosage and Administration (2.3)].

Advise the patient to read the FDA-approved patient labeling (Patient Information).

60 mg tablets: yellow, oval, biconvex, film-coated, debossed with "L6" on one side and the Boehringer Ingelheim company symbol on the other side. They are packaged in a bottle containing two silica gel desiccants and with a child-resistant closure, available as follows:

Avoid concomitant use of HERNEXEOS with strong CYP3A inducers. If concomitant use cannot be avoided, increase HERNEXEOS dose as recommended [see Dosage and Administration (2.4)].

Zongertinib is a CYP3A substrate. Strong CYP3A4 inducers decrease zongertinib exposure [see Clinical Pharmacology (12.3)], which may reduce effectiveness of HERNEXEOS.

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.

HERNEXEOS can cause severe and life-threatening interstitial lung disease (ILD)/pneumonitis.

In the pooled safety population [see Adverse Reactions (6.1)], 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 [see Dosage and Administration (2.3)].

In a 4-week repeat-dose toxicology study in dogs, oral administration of zongertinib induced lesions of the oral mucosa (hard palate, buccal mucosa, tongue, lips) at doses ≥ 10 mg/kg/day (≥ 0.3 times the human exposure based on AUC at the recommended dose), which correlated with histologic erosion/ulcer and impaired food consumption. These findings were not present following a 4-week recovery period.

The recommended dose reductions for adverse reactions are presented in Table 1.

The recommended dosage modifications for adverse reactions are presented in Table 2.

Based on findings from animal studies and its mechanism of action, HERNEXEOS can cause embryo-fetal harm when administered to a pregnant woman [see Use in Specific Populations (8.1)].

NDC 0597-9257-59

HERNEXEOS^®

(zongertinib tablets)

60 mg

Pharmacist: Store and dispense in the

original container to protect from moisture.

30 tablets

Rx only

Boehringer

Ingelheim

NDC 0597-9257-86

HERNEXEOS^®

(zongertinib tablets)

60 mg

Pharmacist: Store and dispense in the

original container to protect from moisture.

60 tablets

Rx only

Boehringer

Ingelheim

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.

Storage and Handling

Store at 20°C to 25°C (68°F to 77°F), excursions permitted to 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature].

Store in the original container to protect from moisture. Keep the bottle tightly closed. Do not remove the desiccants. Once opened, use within 3 months. Discard any unused tablets 3 months after opening the bottle.

Overdose in one patient who ingested 600 mg of HERNEXEOS resulted in nausea and vomiting.

HERNEXEOS tablets for oral administration contain zongertinib, a kinase inhibitor. The chemical name of zongertinib is 2-Propenamide, N-[1-[8-[[3-methyl-4-[(1-methyl-1H-benzimidazol-5-yl)oxy]phenyl] amino]pyrimido[5,4-d]pyrimidin-2-yl]-4-piperidinyl]-. Its molecular formula is C₂₉H₂₉N₉O₂ and the molecular weight is 535.6. The structural formula is:

Zongertinib is a yellow to dark yellow or orange solid. Zongertinib is slightly soluble at pH 1.2, and practically insoluble at pHs 3.6, 4.5, 5.4 and 6.8.

Each film-coated tablet of HERNEXEOS contains 60 mg of zongertinib and the following inactive ingredients: colloidal silicon dioxide, croscarmellose sodium, hypromellose acetate succinate, mannitol, microcrystalline cellulose, and sodium stearyl fumarate. In addition, the film-coating contains the following inactive ingredients: ferric oxide (yellow), glycerol mono and dicaprylocaprate, polyvinyl alcohol, sodium lauryl sulfate, talc, and titanium dioxide.

The safety and effectiveness of HERNEXEOS have not been established in pediatric patients.

Of the 292 patients with non-squamous NSCLC with HER2 (ERBB2) mutations who received HERNEXEOS in clinical studies, 47% were 65 years of age and older and 13% were 75 years and older. No overall differences in safety or effectiveness of HERNEXEOS were observed between older and younger adult patients.

HERNEXEOS can cause severe and life-threatening hepatotoxicity, including drug induced liver injury. In the pooled safety population [see Adverse Reactions (6.1)], 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 [see Dosage and Administration (2.3)].

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).

None.

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)]

• Strong CYP3A Inducers: Avoid concomitant use with strong CYP3A inducers. If concomitant use cannot be avoided, increase HERNEXEOS dose. (7.1)
• BCRP Substrates: Avoid concomitant use with certain BCRP substrates where minimal concentration increase may lead to serious adverse reactions and consider alternative therapies. If concomitant use cannot be avoided, monitor patients closely for adverse reactions and follow recommendations provided in the BCRP substrate approved product labeling. For other BCRP substrates, monitor for increased adverse reactions and adjust the dosages of those substrates as clinically appropriate. (7.2)

The exposure-response relationship and time-course of pharmacodynamic response of zongertinib have not been fully characterized.

Zongertinib pharmacokinetics were observed at steady state in patients with advanced or metastatic solid tumors with HER2 aberrations at the approved recommended dosage and are presented as geometric mean (CV%), unless otherwise specified.

Zongertinib maximum concentration (C_max,ss) is 3.0 (37%) µmol/L and the total systemic exposure (AUC) is 34 (34%) µmol*h/L following HERNEXEOS 120 mg orally daily. Zongertinib C_max and AUC increase in an approximately dose proportional manner across the dose range of 60 mg (0.5 times the approved recommended dosage) to 360 mg (3 times the approved recommended dosage). Zongertinib accumulation is approximately 1.5-fold for AUC and 1.3-fold for C_max at the approved recommended dosage. Steady state is achieved within 2.5 days.

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.

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.

Zongertinib is a kinase inhibitor of human epidermal growth factor receptor 2 (HER2). In vitro, zongertinib inhibited phosphorylation of HER2, downstream signaling of HER2 (phosphorylation of ERK), and proliferation of lung cancer cells harboring HER2 tyrosine kinase domain activating mutations. In vivo, zongertinib demonstrated anti-tumor activity in mouse xenograft models of NSCLC harboring HER2 tyrosine kinase domain activating mutations.

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 [see Use in Specific Populations (8.1, 8.3)].

• 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)

60 mg tablets: yellow, oval, biconvex, film-coated tablets, debossed with "L6" on one side and the Boehringer Ingelheim company symbol on the other side. Each tablet contains 60 mg of zongertinib.

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%).

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 [see Adverse Reactions (6.1)], 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 [see Dosage and Administration (2.3)].

Advise the patient to read the FDA-approved patient labeling (Patient Information).

60 mg tablets: yellow, oval, biconvex, film-coated, debossed with "L6" on one side and the Boehringer Ingelheim company symbol on the other side. They are packaged in a bottle containing two silica gel desiccants and with a child-resistant closure, available as follows:

Avoid concomitant use of HERNEXEOS with strong CYP3A inducers. If concomitant use cannot be avoided, increase HERNEXEOS dose as recommended [see Dosage and Administration (2.4)].

Zongertinib is a CYP3A substrate. Strong CYP3A4 inducers decrease zongertinib exposure [see Clinical Pharmacology (12.3)], which may reduce effectiveness of HERNEXEOS.

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.

HERNEXEOS can cause severe and life-threatening interstitial lung disease (ILD)/pneumonitis.

In the pooled safety population [see Adverse Reactions (6.1)], 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 [see Dosage and Administration (2.3)].

In a 4-week repeat-dose toxicology study in dogs, oral administration of zongertinib induced lesions of the oral mucosa (hard palate, buccal mucosa, tongue, lips) at doses ≥ 10 mg/kg/day (≥ 0.3 times the human exposure based on AUC at the recommended dose), which correlated with histologic erosion/ulcer and impaired food consumption. These findings were not present following a 4-week recovery period.

The recommended dose reductions for adverse reactions are presented in Table 1.

The recommended dosage modifications for adverse reactions are presented in Table 2.

Based on findings from animal studies and its mechanism of action, HERNEXEOS can cause embryo-fetal harm when administered to a pregnant woman [see Use in Specific Populations (8.1)].

NDC 0597-9257-59

HERNEXEOS^®

(zongertinib tablets)

60 mg

Pharmacist: Store and dispense in the

original container to protect from moisture.

30 tablets

Rx only

Boehringer

Ingelheim

NDC 0597-9257-86

HERNEXEOS^®

(zongertinib tablets)

60 mg

Pharmacist: Store and dispense in the

original container to protect from moisture.

60 tablets

Rx only

Boehringer

Ingelheim