Drug Trials Snapshot: HYRNUO
HOW TO USE THIS SNAPSHOT
The information provided in Snapshots highlights who participated in the key clinical trials that supported the original FDA approval of this drug, and whether there were differences among sex, race, age, and ethnic groups. The “MORE INFO” bar shows more detailed, technical content for each section. The Snapshot is intended as one tool for consumers to use when discussing the risks and benefits of the drugs.
LIMITATIONS OF THIS SNAPSHOT:
Do not rely on Snapshots to make decisions regarding medical care. Always speak to your healthcare provider about the benefits and risks of a drug.
Some of the information in this Snapshot is for presentation purposes and does not represent the approved conditions of use of this drug. Refer to the HYRNUO Prescribing Information for all the approved conditions of use of this drug (e.g., indication(s), population(s), dosing regimen(s), safety information).
Snapshots are limited to the information available at the time of the original approval of the drug and do not provide information on who participated in clinical trials that supported later approvals for additional uses of the drug (if applicable).
HYRNUO (sevabertinib)
Her noo' oh
Bayer
Original Approval date: November 19, 2025
DRUG TRIALS SNAPSHOT SUMMARY:
What is the drug for?
HYRNUO is a tyrosine-kinase inhibitor that is indicated for the treatment of adult patients with non-squamous non-small cell lung cancer (NSCLC) caused by abnormal HER2 (ERBB2) gene mutation in the tyrosine kinase domain (TKD) that is locally advanced or has spread to other parts of the body (metastatic), and who have received a prior systemic therapy.
How is this drug used?
HYRNUO is a 10 mg tablet taken by mouth at 20 mg twice daily with food.
Who participated in the clinical trials?
The FDA approved HYRNUO based on evidence from 122 patients with non-squamous NSCLC and HER2 (ERBB2) mutations that had spread beyond the lungs who received HYRNUO 20 mg orally twice daily, enrolled in the SOHO-01 clinical trial (NCT05099172) which was conducted globally at 78 sites in 15 countries including Belgium, Brazil, China, France, Hong Kong, Israel, Italy, Japan, Netherlands, Portugal, Singapore, South Korea, Spain, Taiwan, and the United States.
The efficacy of HYRNUO was evaluated in two subgroups of patients:
- Patients with non-squamous NSCLC with HER2 (ERBB2) TKD mutations that had spread beyond the lungs who had received prior systemic therapy and were HER2-targeted drug naïve (first HER2-targeted drug), classified as Group D. Among these 70 patients the median age was 59 years (range 29 to 77 years); 67% were female; 70% were Asian, 23% were White, 1.4% were Black or African American, 6% were with race not reported; and 2.9% were of Hispanic or Latino ethnicity.
- Patients with non-squamous NSCLC with HER2 (ERBB2) TKD mutations that had spread beyond the lungs who had received prior systemic therapy, including HER2-targeted antibody-drug conjugates (ADCs), classified as Group E. Among these 52 patients the median age was 65 years (range 35 to 91 years); 67% were female; 62% were Asian, 27% were White, 6% were Black or African American, 6% were with race not reported; and 1.9% were of Hispanic or Latino ethnicity.
The safety of HYRNUO was evaluated in 268 patients with NSCLC who received at least one 20 mg twice daily dose of HYRNUO, including 136 patients with HER2 activating mutations who had received prior systemic therapies (Groups D and E). In the 136 patients, the median age was 62 years (range 29 to 91 years); 63% were female; 65% were Asian, 27% White, 3.7% Black or African American; and 2.2% were of Hispanic or Latino ethnicity. The number of patients included in the efficacy analysis differs from the number of patients included in the safety analysis due to different groups of study participants analyzed for efficacy and safety.
How were the trials designed?
The efficacy of HYRNUO was evaluated in 122 patients with non-squamous NSCLC with HER2 mutations that had spread beyond the lungs. This evaluation was conducted across two cohorts (Groups D and E) from the SOHO-01 trial, which is a global, multicenter, single-arm, open-label clinical study with multiple cohorts. Group D included patients who had received prior systemic therapy but were naïve to HER2-targeted therapies (first HER2-targeted drug), while Group E consisted of patients who had received prior systemic therapy, including HER2-targeted antibody-drug conjugates (ADCs). All patients received HYRNUO 20 mg twice daily until either the cancer progressed, or intolerable side effects developed.
The efficacy of HYRNUO was assessed by measuring the percentage of patients who achieved a complete or partial reduction in their tumors (overall response rate or ORR) according to the Response Evaluation Criteria in Solid Tumors (RECIST v1.1), as evaluated by blinded independent central review (BICR) and by measuring the duration of that benefit before the cancer started to grow again (duration of response or DOR).
SOHO-01 is a global, multicenter, single-arm, open-label clinical trial. Patients were required to have histologically or cytologically confirmed, locally advanced or metastatic, HER2-mutant NSCLC, Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, and measurable disease per RECIST v1.1. Patients received HYRNUO at a dose of 20 mg orally twice daily. The major efficacy outcome measures were confirmed ORR and DOR according to RECIST v1.1 as assessed by a BICR. Tumor assessments with imaging were performed every 6 weeks for the first 36 weeks, every 9 weeks thereafter. The efficacy populations included 122 patients who received prior systemic treatment.
DEMOGRAPHICS SNAPSHOT
Figure 1 summarizes male and female patients enrolled in SOHO-01 of 122 patients with advanced non-squamous NSCLC with HER2 (ERBB2) TKD activating mutations based on prospective local testing.
Figure 1. Baseline Demographics by Sex for Groups D and E, Efficacy Population
Source: Adapted from FDA Review
Figure 2 summarizes baseline demographics by race in SOHO-01.
Figure 2. Baseline Demographics by Race for Groups D and E, Efficacy Population
Source: Adapted from FDA Review
Figure 3 summarizes baseline demographics by age in SOHO-01.
Figure 3. Baseline Demographics by Age for Groups D and E, Efficacy Population
Source: Adapted from FDA Review
Figure 4 summarizes baseline demographics by ethnicity enrolled in SOHO-01.
Figure 4. Baseline Demographics by Ethnicity for Groups D and E, Efficacy Population
Source: Adapted from FDA Review
Who participated in the trials?
Table 1. Baseline Demographics for Groups D and E, Efficacy Population
| Demographic | Group D N=70 n (%) |
Group E N=52 n (%) |
Total N=122 n (%) |
|---|---|---|---|
| Age, years | |||
| <65 | 49 (70.0) | 25 (48.1) | 74 (60.7) |
| ≥65 | 21 (30.0) | 27 (51.9) | 48 (39.3) |
| Sex | |||
| Male | 23 (32.9) | 17 (32.7) | 40 (32.8) |
| Female | 47 (67.1) | 35 (67.3) | 82 (67.2) |
| Race | |||
| Asian | 49 (70.0) | 32 (61.5) | 81 (66.4) |
| White | 16 (22.9) | 14 (26.9) | 30 (24.6) |
| Black or African American | 1 (1.4) | 3 (5.8) | 4 (3.3) |
| Not reported | 4 (5.7) | 3 (5.8) | 7 (5.7) |
| Ethnicity | |||
| Not Hispanic or Latino | 62 (88.6) | 48 (92.3) | 110 (90.2) |
| Hispanic or Latino | 2 (2.9) | 1 (1.9) | 3 (2.5) |
| Not reported | 6 (8.6) | 3 (5.8) | 9 (7.4) |
Source: Adapted from FDA Review
Group D: HER2-targeted therapy naïve
Group E: Prior HER2 ADC
Abbreviations: ADC, antibody-drug conjugate
What are the benefits of this drug?
In Group D of the SOHO-01 trial, 71% of the 70 patients with non-squamous NSCLC and HER2 (ERBB2) TKD mutations who had received prior systemic therapy and were HER2-targeted drug naïve (first HER2-targeted drug) experienced complete or partial shrinkage of their tumors. Among 50 patients who had complete or partial tumor shrinkage, 54% had complete or partial shrinkage of their tumors which lasted more than 6 months, while for 18% this lasted for more than 12 months.
In Group E of the SOHO-01 trial, 38% of the 52 patients with non-squamous NSCLC with HER2 (ERBB2) TKD mutations who had received prior systemic therapy, including HER2-targeted antibody-drug conjugates (ADCs), experienced complete or partial shrinkage of their tumors. Among 20 responding patients, 60% had complete or partial shrinkage of their tumors which lasted more than 6 months, while for 10% this lasted for more than 12 months.
HYRNUO was approved under FDA’s accelerated approval program, which provides earlier patient access to a promising new drug while the company continues to conduct clinical trials to confirm that the drug works well.
What are the benefits of this drug (results of trials used to assess efficacy)?
Table 2. Efficacy Results for SOHO-01, Groups D and E, Efficacy Population
| Efficacy Parameter | Group D N=70 |
Group E N=52 |
|---|---|---|
| Objective response ratea, (95% CI) | 71% (59, 82) | 38% (25, 53) |
Complete response |
2.90% | 6% |
Partial response |
69% | 33% |
| Duration of responsec | N=50 | N=20 |
Median, months (95% CI)b |
9.2 (6.3, 15.0) | 7.0 (5.6, NE) |
DOR ≥6 monthsc |
54% | 60% |
DOR ≥12 monthsc |
18% | 10% |
Source: HYRNUO Prescribing Information
a ORR 95% CI calculated using Clopper-Pearson method
b Kaplan-Meier estimate
c Observed proportion of responding patients with duration of response beyond landmark time
Group D: HER2-targeted therapy naïve
Group E: Prior HER2 ADC
Abbreviations: ADC, antibody-drug conjugate; CI, confidence interval; DOR, duration of response; NE, not evaluable; ORR, objective response rate
Were there any differences in how well the drug worked in clinical trials among sex, race, and age?
Sex: The effect of HYRNUO was similar in females and males.
Race: HYRNUO worked similarly in Asian and White patients. The number of patients of other races was small; therefore, differences in how the drug worked in other races could not be determined.
- Age: HYRNUO appears to work similarly in patients younger and older than 65 years of age; however, the number of enrolled patients older than 65 years old is limited.
Were there any differences in how well the drug worked in clinical trials among sex, race, and age groups?
Table 3. Efficacy Results by Subgroup, Group D, Efficacy Population
| Subgroup | Group D, N=70 | |
|---|---|---|
| n/Ns | ORRa (95% CI) | |
| Overall | 50/70 | 71.4 (59.4, 81.6) |
| Age, years | ||
<65 |
35/49 | 71.4 (56.7, 83.4) |
≥65 |
15/21 | 71.4 (47.8, 88.7) |
| Sex | ||
Male |
17/23 | 73.9 (51.6, 89.8) |
Female |
33/47 | 70.2 (55.1, 82.7) |
| Race | ||
Asian |
34/49 | 69.4 (54.6, 81.7) |
White |
13/16 | 81.3 (54.4, 96.0) |
Otherb |
3/5 | NC |
| Ethnicity | ||
Not Hispanic or Latino |
44/62 | 71.0 (58.1, 81.8) |
Hispanic or Latino |
2/2 | NC |
Not reported |
4/6 | NC |
Source: Adapted from FDA Review
a ORR 95% CI calculated using Clopper-Pearson method
b Other includes Black or African American and not reported
Group D: HER2-targeted therapy naïve
Abbreviations: CI, confidence interval; n, number of patients with complete response or partial response; NC, not calculable; Ns, total number of patients for each specific subgroup and were assigned to that specific arm; ORR, objective response rate
Table 4. Efficacy Results by Subgroup, Group E, Efficacy Population
|
Subgroup |
Group E, N=52 |
|
|---|---|---|
|
n/Ns |
ORRa (95% CI) |
|
|
Overall |
20/52 |
38.5 (25.3, 53.0) |
| Age, years | ||
|
11/25 |
44.0 (24.4,65.1) |
|
9/27 |
33.3 (16.5, 54.0) |
| Sex | ||
|
5/17 |
29.4 (10.3, 56.0) |
|
15/35 |
42.9 (26.3, 60.6) |
| Race | ||
|
15/32 |
46.9 (29.1, 65.3) |
|
3/14 |
21.4 (4.7, 50.8) |
|
2/6 |
33.3 (4.3, 77.7) |
|
Ethnicity | ||
|
19/48 |
39.6 (25.8, 54.7) |
|
1/1 |
NC |
|
0/3 |
NC |
Source: Adapted from FDA Review
a ORR 95% CI calculated using Clopper-Pearson method
b Other includes Black or African American and not reported
Group E: Prior HER2 ADC
Abbreviations: ADC, antibody-drug conjugate; CI, confidence interval; n, number of patients with complete response or partial response; NC, not calculable; Ns, total number of patients for each specific subgroup and were assigned to that specific arm; ORR, objective response rate
What are the possible side effects?
HYRNUO may cause serious side effects including diarrhea; liver problems; lung problems; eye problems; pancreas problems, and harm to an unborn baby (if taken while pregnant).
The most common side effects of HYRNUO include:
- diarrhea
- rash
- paronychia (nail problems)
- stomatitis (mouth sores)
- nausea
- changes in certain blood tests
What are the possible side effects (results of trials used to assess safety)?
Table 5 and Table 6 summarize adverse reactions and laboratory abnormalities that occurred in NSCLC patients with HER2 activating mutations who received prior systemic therapies (Groups D and E).
Table 5. Adverse Reactions (≥10%) in Patients With NSCLC With HER2 Activating Mutations Who Received HYRNUO in SOHO-01, Groups D and E
| Adverse Reactiona | HYRNUO, N=136 | |
|---|---|---|
| All Grades % | Grade 3 or 4b % | |
| Gastrointestinal disorders | ||
Diarrhea1 |
87 | 18 |
Stomatitis2 |
29 | 1.5 |
Nausea |
21 | 1.5 |
Vomiting |
15 | 2.2 |
Abdominal pain3 |
10 | 0 |
Skin and subcutaneous tissue disorders | ||
Rash4 |
66 | 1.5 |
Paronychia5 |
33 | 0 |
Dry skin6 |
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 | ||
Fatigue7 |
13 | 0.7 |
| Eye disorders | ||
Ocular toxicity8 |
16 | 0.7 |
| Respiratory disorders | ||
Dyspnea9 |
10 | 1.5 |
Source: HYRNUO Prescribing Information
a Graded per NCI CTCAE version 5.
b All were grade 3, except for dyspnea (0.7%, grade 4).
1 Includes diarrhea and enterocolitis.
2 Includes cheilitis, mouth ulceration, mucosal inflammation, and stomatitis.
3 Includes abdominal pain and abdominal pain upper.
4 Includes dermatitis acneiform, eczema, eczema asteatotic, palmar-plantar erythrodysaesthesia syndrome, rash, rash erythematous, rash maculopapular, rash pruritic, rash pustular, and skin exfoliation.
5 Includes ingrowing nail, nail disorder, onychoclasis, onycholysis, onychomadesis, and paronychia.
6 Includes dry skin and xeroderma.
7 Includes asthenia and fatigue.
8 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, and xerophthalmia.
9 Includes dyspnea and dyspnea exertional.
Group D: HER2-targeted therapy naïve
Group E: Prior HER2 ADC
Abbreviations: ADC, antibody-drug conjugate; NCI CTCAE, National Cancer Institute Common Terminology Criteria for Adverse Events; NSCLC, non-small cell lung cancer
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, and tachycardia), and alopecia (3.7%).
Table 6. 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=136a | |
|---|---|---|
| All Grades %c | Grade 3 or 4b% | |
| 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 increasedd |
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 |
Source: HYRNUO Prescribing Information
a 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.
b All were grade 3, except for calcium decreased (0.7%, grade 4) and amylase increased (1.5%; grade 4)
c Graded per NCI CTCAE version 5.0 using only numeric values.
d Graded per NCI CTCAE version 4.03 using only numeric values.
Group D: HER2-targeted therapy naïve
Group E: Prior HER2 ADC
Abbreviations: ADC, antibody-drug conjugate; NCI CTCAE, National Cancer Institute Common Terminology Criteria for Adverse Events; NSCLC, non-small cell lung cancer
Laboratory abnormalities in <20% of patients who received HYRNUO include blood bilirubin increased (14%; all were grades 1 and 2).
Were there any differences in side effects among sex, race, and age?
- Sex: The occurrence of side effects was similar in males and females. The occurrences of adverse reactions leading to dose reductions were higher in female patients compared to male patients.
- Race: The occurrence of side effects wassimilar across races. The occurrences of grade 3 or higher adverse reactions, and adverse reactions leading to treatment interruptions or dose reductions were higher in White patients compared to Asian patients.
- Age: The occurrence of side effects was similar in patients younger and older than 65 years of age; severe diarrhea was more common in adults 75 years and older (23%) than younger patients (14%). The occurrences of adverse reactions leading to treatment interruptions or dose reductions were higher in patients who were older than 65 years of age compared to patients 65 years old or younger.
Were there any differences in side effects of the clinical trials among sex, race, and age groups?
Table 7. Side Effects by Sex for Patients Who Received HYRNUO 20 mg Twice Daily in Groups D and E
| Parameter | Male N=50 n (%) |
Female N=86 n (%) |
|---|---|---|
| All-grade TEAEs | 50 (100.0) | 86 (100.0) |
| Grade ≥3 TEAEs | 26 (52.0) | 41 (47.7) |
| Serious TEAEs | 17 (34.0) | 25 (29.1) |
| TEAEs leading to dose reductions | 10 (20.0) | 28 (32.6) |
| TEAEs leading to dose interruptions/delays | 21 (42.0) | 42 (48.8) |
| TEAEs leading to permanent discontinuation of study drug | 2 (4.0) | 3 (3.5) |
Source: Adapted from FDA Review
Group D: HER2-targeted therapy naïve
Group E: Prior HER2 ADC
Abbreviations: ADC, antibody-drug conjugate; TEAE, treatment-emergent adverse event
Table 8. Side Effects by Race for Patients Who Received HYRNUO 20 mg Twice Daily in Groups D and E
| Parameter | Asian N=89 n (%) |
White N=33 n (%) |
Other1 N=14 n (%) |
|---|---|---|---|
| All-grade TEAEs | 89 (100.0) | 33 (100.0) | 14 (100.0) |
| Grade ≥3 TEAEs | 42 (47.2) | 21 (63.6) | 4 (28.6) |
| Serious TEAEs | 27 (30.3) | 13 (39.4) | 2 (14.3) |
| TEAEs leading to dose reductions | 23 (25.8) | 14 (42.4) | 1 (7.1) |
| TEAEs leading to dose interruptions/delays | 36 (40.4) | 24 (72.7) | 3 (21.4) |
| TEAEs leading to permanent discontinuation of study drug | 3 (3.4) | 1 (3.0) | 1 (7.1) |
Source: Adapted from FDA Review
1 Other includes Black or African American and not reported
Group D: HER2-targeted therapy naïve
Group E: Prior HER2 ADC
Abbreviations: ADC, antibody-drug conjugate; TEAE, treatment-emergent adverse event
Table 9. Side Effects by Age for Patients Who Received HYRNUO 20 mg Twice Daily in Groups D and E
| Parameter | ≤65 Years N=82 n (%) |
>65 Years N=54 n (%) |
|---|---|---|
| All-grade TEAEs | 82 (100.0) | 54 (100.0) |
| Grade ≥3 TEAEs | 41 (50.0) | 26 (48.1) |
| Serious TEAEs | 24 (29.3) | 18 (33.3) |
| TEAEs leading to dose reductions | 19 (23.2) | 19 (35.2) |
| TEAEs leading to dose interruptions/delays | 32 (39.0) | 31 (57.4) |
| TEAEs leading to permanent discontinuation of study drug | 3 (3.7) | 2 (3.7) |
Source: Adapted from FDA Review
Group D: HER2-targeted therapy naïve
Group E: Prior HER2 ADC
Abbreviations: ADC, antibody-drug conjugate; TEAE, treatment-emergent adverse event
GLOSSARY
CLINICAL TRIAL: Voluntary research studies conducted in people and designed to answer specific questions about the safety or effectiveness of drugs, vaccines, other therapies, or new ways of using existing treatments.
COMPARATOR: A previously available treatment or placebo used in clinical trials that is compared to the actual drug being tested.
EFFICACY: How well the drug achieves the desired response when it is taken as described in a controlled clinical setting, such as during a clinical trial.
PLACEBO: An inactive substance or “sugar pill” that looks the same as, and is given the same way as, an active drug or treatment being tested. The effects of the active drug or treatment are compared to the effects of the placebo.
SUBGROUP: A subset of the population studied in a clinical trial. Demographic subsets include sex, race, and age groups.
Legal Disclaimer:
EIN Presswire provides this news content "as is" without warranty of any kind. We do not accept any responsibility or liability for the accuracy, content, images, videos, licenses, completeness, legality, or reliability of the information contained in this article. If you have any complaints or copyright issues related to this article, kindly contact the author above.
