HYRNUO
Generic: SEVABERTINIB
Basic Information
Manufacturer
Bayer HealthCare Pharmaceuticals Inc.
Product Type
HUMAN PRESCRIPTION DRUG
Route of Administration
ORAL
FDA Set ID
d7a11334-6e7a-445b-9a16-bdcd9acbe61f
Indications & 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.
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.
Adverse Reactions
6 ADVERSE REACTIONS The following clinically significant adverse reactions are discussed in greater detail in other sections of the labeling: Diarrhea [see Warnings and Precautions (5.1) ] Hepatotoxicity [see Warnings and Precautions (5.2) ] Interstitial Lung Disease (ILD)/Pneumonitis [see Warnings and Precautions (5.3) ] Ocular Toxicity [see Warnings and Precautions (5.4) ] Pancreatic Enzyme Elevation [see Warnings and Precautions (5.5) ] Most common adverse reactions (>20%) : diarrhea, rash, paronychia, stomatitis, and nausea.
Most common Grade 3 or 4 laboratory abnormalities (≥2%) : decreased potassium, increased lipase, decreased lymphocyte count, decreased sodium, increased amylase, increased ALT, and increased AST.
( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Bayer HealthCare Pharmaceuticals Inc.
at 1-888-842-2937 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .
6.1 Clinical Trial 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 practice.
The pooled safety population in the WARNINGS AND PRECAUTIONS reflects exposure to HYRNUO at 20 mg orally twice daily in 268 patients with locally advanced or metastatic NSCLC harboring HER2 and/or other mutations from the SOHO-01 study [see Clinical Studies (14) ] .
Among 268 patients who received HYRNUO, 35% were exposed for greater than 6 months and 12% were exposed for greater than 1 year.
In this pooled safety population, the most common (>20%) adverse reactions were diarrhea, rash, stomatitis, and paronychia.
The most common (≥2%) Grade 3 or 4 laboratory abnormalities were decreased potassium, increased lipase, decreased lymphocyte count, decreased sodium, increased amylase, increased ALT, and increased AST.
The safety of HYRNUO at 20 mg orally twice daily was evaluated in 136 patients with locally advanced or metastatic NSCLC harboring HER2 activating mutations who had received prior systemic therapy in the SOHO-01 study [see Clinical Studies (14) ] .
Among 136 patients who received HYRNUO, 46% were exposed greater than 6 months and 15% were exposed for greater than 1 year.
The median age of patients who received HYRNUO was 62 years (range: 29 to 91); 63% female; 65% Asian, 27% White, 3.7% Black or African American; and 2.2% were of Hispanic or Latino ethnicity.
The most common adverse reactions (>20%) in patients who received HYRNUO were diarrhea, rash, paronychia, stomatitis, and nausea.
The most common Grade 3 or 4 laboratory abnormalities (≥2%) were potassium decreased, lipase increased, lymphocyte count decreased, sodium decreased, amylase increased, aspartate aminotransferase (AST) increased, and alanine aminotransferase (ALT) increased.
Serious adverse reactions occurred in 31% of patients who received HYRNUO.
Serious adverse reactions in ≥2% of patients were diarrhea (6%), pneumonia (3.7%), dyspnea (2.2%), and pleural effusion (2.2%).
Permanent discontinuation of HYRNUO due to an adverse reaction occurred in 3.7% of patients.
Adverse reactions which resulted in permanent discontinuation were corneal epithelial microcysts, hepatic function abnormal, electrocardiogram QT prolonged, pain in extremity and dyspnea (0.7%, 1 patient each).
Dosage interruptions of HYRNUO due to an adverse reaction occurred in 46% of patients.
Adverse reactions which resulted in dosage interruptions in >3% of patients were diarrhea, hypokalemia, nausea, decreased appetite, and pneumonia.
Dose reductions of HYRNUO due to adverse reactions occurred in 28% of patients.
Adverse reactions which resulted in dose reductions in >2% of patients were diarrhea, rash, and hypokalemia.
Table 4 summarizes the adverse reactions in SOHO-01 (Groups D and E).
Table 4: Adverse Reactions (≥10%) in Patients with NSCLC with HER2 Activating Mutations Who Received HYRNUO in SOHO-01 (Groups D and E) Adverse Reaction Graded per NCI CTCAE version 5.
HYRNUO N = 136 All Grades (%) Grade 3 or 4 All were Grade 3, except for dyspnea (0.7%, Grade 4).
(%) Gastrointestinal disorders Diarrhea Includes diarrhea, enterocolitis.
87 18 Stomatitis Includes cheilitis, mouth ulceration, mucosal inflammation, stomatitis.
29 1.5 Nausea 21 1.5 Vomiting 15 2.2 Abdominal pain Includes abdominal pain, abdominal pain upper.
10 0 Skin and subcutaneous tissue disorders Rash Includes dermatitis acneiform, eczema, eczema asteatotic, palmar-plantar erythrodysaesthesia syndrome, rash, rash erythematous, rash maculopapular, rash pruritic, rash pustular, skin exfoliation.
66 1.5 Paronychia Includes ingrowing nail, nail disorder, onychoclasis, onycholysis, onychomadesis, paronychia.
33 0 Dry skin Includes dry skin, xeroderma.
20 0 Pruritus 14 1.5 Metabolism and nutrition disorders Decreased appetite 18 2.9 Investigations Weight decreased 19 0.7 General disorders and administration site conditions Fatigue Includes asthenia, fatigue.
13 0.7 Eye disorders Ocular toxicity Includes blindness unilateral, cataract, conjunctivitis, conjunctivitis allergic, corneal epithelial microcysts, dry eye, eye discharge, eye pain, lacrimation increased, ocular hyperemia, ocular hypertension, ocular toxicity, vision blurred, visual acuity reduced, visual impairment, xerophthalmia.
16 0.7 Respiratory disorders Dyspnea Includes dyspnea, dyspnea exertional.
10 1.5 Clinically relevant adverse reactions in <10% of patients who received HYRNUO included edema (8%), cardiac arrhythmia (6%; includes arrhythmia, atrioventricular block complete, electrocardiogram QT prolonged, sinus bradycardia, sinus tachycardia, supraventricular extrasystoles, supraventricular tachycardia, tachycardia) and alopecia (3.7%).
Table 5 summarizes the laboratory abnormalities observed in SOHO-01 (Groups D and E).
Table 5: Select Laboratory Abnormalities (≥20%) That Worsened from Baseline in Patients with NSCLC with HER2 Activating Mutations in SOHO-01 (Groups D and E) Laboratory Abnormality HYRNUO N=136 The denominator used to calculate the rate varied from 103 to 135 based on the number of patients with a baseline value and at least one post-treatment value.
All Grades (%) Graded per NCI CTCAE version 5 using only numeric values.
Grade 3 or 4 All were Grade 3, except for calcium decreased (0.7%, Grade 4) and amylase increased (1.5%; Grade 4) (%) Hematology Hemoglobin decreased 47 1.5 Lymphocyte count decreased 32 6 White blood cell decreased 21 0.7 Chemistry Lipase increased 48 12 Potassium decreased 45 13 Aspartate aminotransferase increased 41 3 Magnesium decreased 40 0 Alanine aminotransferase increased 37 3 Glucose increased Graded per NCI CTCAE version 4.03 using only numeric values.
36 0.7 Albumin decreased 32 1.5 Amylase increased 31 3.8 Calcium decreased 28 1.5 Creatinine increased 27 0 Sodium decreased 26 4.4 Alkaline phosphatase increased 24 0 Triglycerides increased 22 0 Laboratory abnormalities in <20% of patients who received HYRNUO include blood bilirubin increased (14%; all were Grades 1 and 2).
Most common Grade 3 or 4 laboratory abnormalities (≥2%) : decreased potassium, increased lipase, decreased lymphocyte count, decreased sodium, increased amylase, increased ALT, and increased AST.
( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Bayer HealthCare Pharmaceuticals Inc.
at 1-888-842-2937 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .
6.1 Clinical Trial 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 practice.
The pooled safety population in the WARNINGS AND PRECAUTIONS reflects exposure to HYRNUO at 20 mg orally twice daily in 268 patients with locally advanced or metastatic NSCLC harboring HER2 and/or other mutations from the SOHO-01 study [see Clinical Studies (14) ] .
Among 268 patients who received HYRNUO, 35% were exposed for greater than 6 months and 12% were exposed for greater than 1 year.
In this pooled safety population, the most common (>20%) adverse reactions were diarrhea, rash, stomatitis, and paronychia.
The most common (≥2%) Grade 3 or 4 laboratory abnormalities were decreased potassium, increased lipase, decreased lymphocyte count, decreased sodium, increased amylase, increased ALT, and increased AST.
The safety of HYRNUO at 20 mg orally twice daily was evaluated in 136 patients with locally advanced or metastatic NSCLC harboring HER2 activating mutations who had received prior systemic therapy in the SOHO-01 study [see Clinical Studies (14) ] .
Among 136 patients who received HYRNUO, 46% were exposed greater than 6 months and 15% were exposed for greater than 1 year.
The median age of patients who received HYRNUO was 62 years (range: 29 to 91); 63% female; 65% Asian, 27% White, 3.7% Black or African American; and 2.2% were of Hispanic or Latino ethnicity.
The most common adverse reactions (>20%) in patients who received HYRNUO were diarrhea, rash, paronychia, stomatitis, and nausea.
The most common Grade 3 or 4 laboratory abnormalities (≥2%) were potassium decreased, lipase increased, lymphocyte count decreased, sodium decreased, amylase increased, aspartate aminotransferase (AST) increased, and alanine aminotransferase (ALT) increased.
Serious adverse reactions occurred in 31% of patients who received HYRNUO.
Serious adverse reactions in ≥2% of patients were diarrhea (6%), pneumonia (3.7%), dyspnea (2.2%), and pleural effusion (2.2%).
Permanent discontinuation of HYRNUO due to an adverse reaction occurred in 3.7% of patients.
Adverse reactions which resulted in permanent discontinuation were corneal epithelial microcysts, hepatic function abnormal, electrocardiogram QT prolonged, pain in extremity and dyspnea (0.7%, 1 patient each).
Dosage interruptions of HYRNUO due to an adverse reaction occurred in 46% of patients.
Adverse reactions which resulted in dosage interruptions in >3% of patients were diarrhea, hypokalemia, nausea, decreased appetite, and pneumonia.
Dose reductions of HYRNUO due to adverse reactions occurred in 28% of patients.
Adverse reactions which resulted in dose reductions in >2% of patients were diarrhea, rash, and hypokalemia.
Table 4 summarizes the adverse reactions in SOHO-01 (Groups D and E).
Table 4: Adverse Reactions (≥10%) in Patients with NSCLC with HER2 Activating Mutations Who Received HYRNUO in SOHO-01 (Groups D and E) Adverse Reaction Graded per NCI CTCAE version 5.
HYRNUO N = 136 All Grades (%) Grade 3 or 4 All were Grade 3, except for dyspnea (0.7%, Grade 4).
(%) Gastrointestinal disorders Diarrhea Includes diarrhea, enterocolitis.
87 18 Stomatitis Includes cheilitis, mouth ulceration, mucosal inflammation, stomatitis.
29 1.5 Nausea 21 1.5 Vomiting 15 2.2 Abdominal pain Includes abdominal pain, abdominal pain upper.
10 0 Skin and subcutaneous tissue disorders Rash Includes dermatitis acneiform, eczema, eczema asteatotic, palmar-plantar erythrodysaesthesia syndrome, rash, rash erythematous, rash maculopapular, rash pruritic, rash pustular, skin exfoliation.
66 1.5 Paronychia Includes ingrowing nail, nail disorder, onychoclasis, onycholysis, onychomadesis, paronychia.
33 0 Dry skin Includes dry skin, xeroderma.
20 0 Pruritus 14 1.5 Metabolism and nutrition disorders Decreased appetite 18 2.9 Investigations Weight decreased 19 0.7 General disorders and administration site conditions Fatigue Includes asthenia, fatigue.
13 0.7 Eye disorders Ocular toxicity Includes blindness unilateral, cataract, conjunctivitis, conjunctivitis allergic, corneal epithelial microcysts, dry eye, eye discharge, eye pain, lacrimation increased, ocular hyperemia, ocular hypertension, ocular toxicity, vision blurred, visual acuity reduced, visual impairment, xerophthalmia.
16 0.7 Respiratory disorders Dyspnea Includes dyspnea, dyspnea exertional.
10 1.5 Clinically relevant adverse reactions in <10% of patients who received HYRNUO included edema (8%), cardiac arrhythmia (6%; includes arrhythmia, atrioventricular block complete, electrocardiogram QT prolonged, sinus bradycardia, sinus tachycardia, supraventricular extrasystoles, supraventricular tachycardia, tachycardia) and alopecia (3.7%).
Table 5 summarizes the laboratory abnormalities observed in SOHO-01 (Groups D and E).
Table 5: Select Laboratory Abnormalities (≥20%) That Worsened from Baseline in Patients with NSCLC with HER2 Activating Mutations in SOHO-01 (Groups D and E) Laboratory Abnormality HYRNUO N=136 The denominator used to calculate the rate varied from 103 to 135 based on the number of patients with a baseline value and at least one post-treatment value.
All Grades (%) Graded per NCI CTCAE version 5 using only numeric values.
Grade 3 or 4 All were Grade 3, except for calcium decreased (0.7%, Grade 4) and amylase increased (1.5%; Grade 4) (%) Hematology Hemoglobin decreased 47 1.5 Lymphocyte count decreased 32 6 White blood cell decreased 21 0.7 Chemistry Lipase increased 48 12 Potassium decreased 45 13 Aspartate aminotransferase increased 41 3 Magnesium decreased 40 0 Alanine aminotransferase increased 37 3 Glucose increased Graded per NCI CTCAE version 4.03 using only numeric values.
36 0.7 Albumin decreased 32 1.5 Amylase increased 31 3.8 Calcium decreased 28 1.5 Creatinine increased 27 0 Sodium decreased 26 4.4 Alkaline phosphatase increased 24 0 Triglycerides increased 22 0 Laboratory abnormalities in <20% of patients who received HYRNUO include blood bilirubin increased (14%; all were Grades 1 and 2).