Drug Trials Snapshots: HERNEXEOS
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 HERNEXEOS 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).
HERNEXEOS (zongertinib)
her-nex-ee-ose
Boehringer Ingelheim Pharmaceuticals, Inc
Approval date: August 8, 2025
DRUG TRIALS SNAPSHOT SUMMARY:
What is the drug for?
HERNEXEOS is a prescription drug used to treat adults 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-approved test, and who have received prior systemic therapy.
How is this drug used?
HERNEXEOS is a tablet that is taken by mouth once daily with or without food.
Who participated in the clinical trials?
The FDA approved HERNEXEOS based on safety and efficacy evidence from one clinical trial (NCT04886804/Beamion LUNG-1) of 105 patients with unresectable or metastatic non-squamous NSCLC whose tumors have HER2 (ERBB2) tyrosine kinase domain activating mutations. All patients had previously received platinum-based chemotherapy. The trial was conducted at 51 sites in 13 countries including the United States, Europe, Israel, Japan, Singapore, South Korea, Australia, and China.
Of the 105 patients, 71 patients had not previously been treated with a HER2-targeted antibody-drug conjugate (ADC), and 34 patients had previously been treated with HER2-targeted ADC. Among the 105 patients, the median age was 61 years (range: 30 to 85 years); 69% were female; 49% were Asian, 40% were White, and 11% were race unknown or not reported; 1.9% were Hispanic or Latino ethnicity; and 9% of patients were from the United States.
How were the trials designed?
The benefits and side effects of HERNEXEOS were evaluated in one clinical trial of 105 patients with NSCLC who had been previously treated with chemotherapy for their advanced cancer and whose tumors harbored HER2 (ERBB2) tyrosine kinase domain activating mutations.
The benefit of HERNEXEOS was evaluated by measuring the percentage of patients who had complete, partial, or minor responses (objective response rate or ORR) assessed by blinded independent central review (BICR) according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, and by measuring the duration of that decrease in tumor size (duration of response or DOR).
Randomization was stratified by prior therapies (<3 versus 3) and baseline brain metastasis (yes versus no). Tumor assessments were conducted every six weeks.
The major efficacy outcome measure was confirmed blinded independent review committee (BIRC) assessed overall response rate (ORR) according to RECIST v1.1. Additional efficacy outcome measure was BIRC-assessed duration of response (DOR).
How were the trials designed?
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 or pneumonitis.
Patients received HERNEXEOS 120 mg orally once daily until disease progression or unacceptable toxicity.
The major efficacy outcome measures were ORR and DOR by RECIST version 1.1 as assessed by BICR.
DEMOGRAPHICS SNAPSHOT
Figure 1 summarizes how many male and female patients were enrolled in the clinical trial used to evaluate the efficacy of HERNEXEOS.
Figure 1. Baseline Demographics by Sex, Efficacy Population
Source: Adapted from HERNEXEOS Prescribing Information
Figure 2 summarizes how many patients by race were enrolled in the clinical trial used to evaluate the efficacy of HERNEXEOS.
Figure 2. Baseline Demographics by Race, Efficacy Population
Adapted from HERNEXEOS Prescribing Information
Figure 3 summarizes how many patients by age were enrolled in the clinical trial used to evaluate the efficacy of HERNEXEOS.
Figure 3. Baseline Demographics by Age, Efficacy Population
Adapted from HERNEXEOS Prescribing Information
Figure 4 summarizes how many patients by ethnicity were enrolled in the clinical trial used to evaluate the efficacy of HERNEXEOS.
Figure 4. Baseline Demographics by Ethnicity, Efficacy Population
Source: Adapted from HERNEXEOS Prescribing Information
Baseline Demographics of Efficacy Trials by Age, Race, Sex, and Ethnicity
Table 1. Number of Patients Enrolled by Sex, Race, Age, and Ethnicity
| Demographic variable | Without Previous HER2-Targeted ADC N=71 |
With Previous HER2‑Targeted ADC |
Overall |
|---|---|---|---|
| All patients | 71 (100) |
34 (100) |
105 (100) |
| Sex | |||
| Female | 50 (70) |
22 (65) |
72 (69) |
| Male | 21 (30) |
12 (35) |
33 (31) |
| Race | |||
| Asian | 39 (55) |
12 (35) |
51 (49) |
| White | 25 (35) |
17 (50) |
42 (40) |
| Missing | 7 (10) |
5 (15) |
12 (11) |
| Ethnicity | |||
| Hispanic or Latino | 1 (1.4) |
1 (2.9) |
2 (1.9) |
| Not Hispanic or Latino | 64 (90) |
29 (85) |
93 (89) |
| Missing | 6 (9) |
4 (12) |
10 (10) |
| Age, years | |||
| 18 to <65 | 41 (58) |
22 (65) |
63 (60) |
| 65 to <75 | 23 (32) |
8 (24) |
31 (30) |
| ≥75 | 7 (10) |
4(12) |
11 (10) |
Source: HERNEXEOS Prescribing Information
Abbreviations: ADC, antibody-drug conjugate
What are the benefits of this drug?
In the Beamion LUNG-1 trial, 75% of the 71 patients previously treated with platinum-based chemotherapy but had not been previously treated with a HER2-targeted tyrosine kinase inhibitor or ADC experienced complete or partial shrinkage of their tumors; 58% of these patients had complete or partial shrinkage of their tumors which lasted 6 months or longer.
In this trial, 44% of the 34 patients previously treated with platinum-based chemotherapy and a HER2-targeted ADC experienced complete or partial shrinkage of their tumors; 27% of these patients had complete or partial shrinkage of their tumors which lasted 6 months or longer.
HERNEXEOS 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 summarizes the results of the major efficacy outcome measures, ORR, and DOR as determined by BICR according to RECIST v1.1 in the 71 patients who received prior platinum-based chemotherapy without previous HER2-targeted ADC and 34 patients who received prior platinum-based chemotherapy and a HER2-targeted ADC.
Table 2. Efficacy Results for Unresectable or Metastatic NSCLC With HER2 (ERBB2) Tyrosine Kinase Domain Activating Mutations Previously Treated
| Efficacy Parameter | Without Previous HER2‑Targeted ADC |
With Previous HER2‑Targeted ADC |
|---|---|---|
| ORR, % (95% CI)1 | 75 (63, 83) |
44(29, 61) |
| Complete response, % | 6 |
2.9 |
| Partial response, % | 69 |
41 |
| DOR | N=53 |
N=15 |
| Range, months | 1.3+, 15+ |
1.7, 12.5+ |
| DOR ≥6 months,2 % | 58 |
27 |
Source: HERNEXEOS Prescribing Information
1 Based on Wilson confidence interval.
2 Based on observed duration of response.
Abbreviation: +, ongoing response; ADC, antibody-drug conjugate; CI, confidence Interval; DOR, duration of response; NSCLC, non-small cell lung cancer; ORR, objective response rate
Were there any differences in how well the drug worked in clinical trials among sex, race, and age?
- Sex: HERNEXEOS worked similarly in males and females.
- Race: HERNEXEOS worked similarly in Asian and White patients. The number of patients in other races was small; therefore, differences in how the drug worked in other races could not be determined.
- Age: HERNEXEOS worked similarly in patients younger and older than 65 years of age.
Were there any differences in how well the drug worked in clinical trials among sex, race, and age groups?
Table 3. Efficacy Results by Sex, Race, Age, and Ethnicity in Patients Without Previous HER2-Targeted ADC
Table 3. Efficacy Results by Sex, Race, and Age, Efficacy Population
| Subgroup | Number of Patients |
ORR |
|---|---|---|
| Sex | ||
| Female | 50 |
78 (64, 88) |
| Male | 21 |
67 (43, 85) |
| Race | ||
| Asian | 39 |
77 (61, 89) |
| White | 25 |
72 (51, 88) |
| Missing | 7 |
71 (29, 96) |
| Ethnicity | ||
| Hispanic or Latino | 1 |
NC |
| Not Hispanic or Latino | 64 |
75 (63, 85) |
| Missing | 6 |
67 (22, 96) |
| Age, years | ||
| <65 | 41 |
68 (52, 82) |
| ≥65 | 30 |
83 (65, 94) |
Source: HERNEXEOS Prescribing Information
1 Based on exact confidence interval.
Abbreviations: ADC, antibody-drug conjugate; CI, confidence Interval; NC, not calculated; ORR, objective response rate
Table 4. Efficacy Results by Sex, Race, Age, and Ethnicity in Patients With Previous HER2-Targeted ADC
| Subgroup | Number of Patients |
ORR |
|---|---|---|
| Sex | ||
| Female | 22 |
55 (32, 76) |
| Male | 12 |
>25 (5, 57) |
| Race | ||
| Asian | 12 |
58 (28, 85) |
| White | 17 |
29 (10, 56) |
| Missing | 5 |
60 (15, 95) |
| Ethnicity | ||
| Hispanic or Latino | 1 |
NC |
| Not Hispanic or Latino | 29 |
41 (24, 61) |
| Missing | 4 |
75 (19, 99) |
| Age, years | ||
| <65 | 22 |
41 (21, 64) |
| ≥65 | 12 |
50 (21, 79) |
Source: HERNEXEOS Prescribing Information
1 Based on exact confidence interval.
Abbreviation: ADC, antibody-drug conjugate; CI, confidence interval; NC, not calculated; ORR, objective response rate
What are the possible side effects?
HERNEXEOS may cause severe and life-threatening liver problems and lung problems. It can also cause severe heart problems that may affect your heart’s ability to pump blood, and harm to unborn babies.
The most common side effects of HERNEXEOS include diarrhea, liver problems, rash, feeling tired, and nausea.
The most common severe abnormal blood tests include decreased white blood cell count and increased liver function tests.
What are the possible side effects (results of trials used to assess safety)?
Table 5. Adverse Reactions (≥15%) in Patients With Non-Squamous NSCLC With HER2 TKD Mutations Who Received HERNEXEOS in Beamion LUNG-1
| Laboratory Parameter | HERNEXEOS, N=105 |
|
|---|---|---|
All Grades1 |
Grade 3 or 4 |
|
| Gastrointestinal disorders | ||
| Diarrhea | 52 | 1 |
| Nausea | 24 | 1 |
| Vomiting | 15 | 1.9 |
| Skin and subcutaneous tissue disorders | ||
| Rash | 32 | 1 |
| Nail disorders | 19 | 0 |
| General disorders | ||
| Fatigue | 25 | 0 |
| Respiratory, thoracic and mediastinal disorders | ||
| Cough | 24 | 0 |
| Dyspnea | 15 | 6 |
| Musculoskeletal and connective tissue disorders | ||
| Musculoskeletal pain | 24 | 1.9 |
| Infections and infestations | ||
| Upper respiratory tract infections | 21 | 0 |
Source: HERNEXEOS Prescribing Information
1 No Grade 4 or Grade 5 adverse reactions occurred.
Events were graded using NCI CTCAE version 5.0.
Abbreviations: NCI CTCAE, National Cancer Institute Common Terminology Criteria for Adverse Events; NSCLC, non-small cell lung cancer; TKD, tyrosine kinase domain
Table 6. 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=105 |
|
|---|---|---|
All Grades1 |
Grade 3 or 4 |
|
| Hematology | ||
| Lymphocytes decreased | 52 |
15 |
| Leukocytes decreased | 43 |
1 |
| Hemoglobin decreased | 37 |
0 |
| Activated partial thromboplastin time increased | 25 |
0 |
| Platelets decreased | 23 |
1 |
| Chemistry | ||
| Alanine aminotransferase increased | 39 |
7 |
| Aspartate aminotransferase increased | 33 |
2.9 |
| Lipase increased | 30 |
0 |
| Bilirubin increased | 26 |
1 |
| Triglycerides increased | 26 |
0 |
| Calcium decreased | 25 |
0 |
| Amylase increased | 24 |
0 |
| Sodium decreased | 23 |
0 |
| Creatinine kinase increased | 22 |
0 |
| Albumin decreased | 21 |
0 |
| Cholesterol increased | 20 |
1.4 |
| Alkaline phosphatase increased |
20
|
1 |
| Magnesium decreased | 20 |
1 |
| Potassium decreased | 20 |
0 |
Source: HERNEXEOS Prescribing Information
1 No Grade 5 adverse reactions occurred.
Events were graded using NCI CTCAE version 5.0.
Abbreviations: NCI CTCAE, National Cancer Institute Common Terminology Criteria for Adverse Events; NSCLC, non-small cell lung cancer; TKD, tyrosine kinase domain
Were there any differences in side effects among sex, race, and age?
- Sex: The occurrence of side effects was similar in males and females.
- Race: The occurrence of side effects was similar in Asian and White patients. The number of patients in other races was small; therefore, differences in the occurrence of side effects in other races could not be determined.
- Age: The occurrence of side effects was similar in patients younger and older than 65 years of age.
Were there any differences in side effects of the clinical trials among sex, race, and age groups?
Table 7. Side Effects by Sex, Race, and Age, Safety Population
| Adverse Reaction | HERNEXEOS, N=105 |
|
|---|---|---|
All Grades | ||
| Sex | Male |
Female |
| Number of patients | 33 (100) |
72 (100) |
| Diarrhea | 10 (30) |
44 (61) |
| Nausea | 3 (9) |
22 (30) |
| Aspartate aminotransferase increased | 4 (12) |
20 (28) |
| Rash | 3 (9) |
21 (29) |
| Anemia | 7 (21) |
16 (22) |
| Cough | 5 (15) |
17 (24) |
| Alanine aminotransferase increased | 3 (9) |
17 (24) |
| Blood creatinine increased | 7 (21) |
9 (13) |
| Race | Asian |
White |
| Number of patients | 51 (100) |
42 (100) |
| Diarrhea | 24 (47) |
25 (60) |
| Nausea | 9 (18) |
12 (29) |
| Aspartate aminotransferase increased | 13 (26) |
8 (19) |
| Rash | 15 (29) |
9 (21) |
| Anemia | 15 (29) |
7 (17) |
| Alanine aminotransferase increased | 12 (24) |
5 (12) |
| Fatigue | 4 (8) |
9 (21) |
| Dyspnea | 4 (8) |
10 (24) |
| White blood cell count decreased | 12 (24) |
3 (7) |
| Neutrophil count decreased | 11 (22) |
1 (2.4) |
| Dry skin | 2 (3.9) |
9 (21) |
| Age group, years | <65 |
≥65 |
| Number of patients | 63 (100) |
42 (100) |
| Diarrhea | 30 (48) |
24 (57) |
| Nausea | 15 (24) |
10 (24) |
| Aspartate aminotransferase increased | 12 (19) |
12 (29) |
| Rash | 13 (21) |
11 (26) |
| Cough | 13 (21) |
9 (21) |
| Anemia | 12 (19) |
11 (26) |
| Alanine aminotransferase increased | 10 (16) |
10 (24) |
| Blood creatinine increased | 7 (11) |
9 (21) |
Source: Adapted from FDA Review
Events were graded using NCI CTCAE version 5.0.
1 No Grade 5 adverse reactions occurred.
Abbreviations: NCI CTCAE, National Cancer Institute Common Terminology Criteria for Adverse Events
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.
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