Zongertinib for Liver Disease

Overseen By Boehringer Ingelheim

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Boehringer Ingelheim

Disqualifiers: Severe hepatic impairment, Severe renal, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 4

Duration: 1 week

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to understand how the body processes a medication called zongertinib in individuals with mild or moderate liver problems. Participants will take a single dose of the medication and undergo regular blood tests and check-ups to monitor their health. The study includes individuals with mild or moderate liver issues and those without liver problems for comparison. It suits individuals with stable liver conditions who manage their liver health without recent treatment changes. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new medication.

Do I have to stop taking my current medications for the trial?

The trial does not require you to stop taking your current medications for liver problems, but your medication regimen must be stable for at least 4 weeks before the trial and should remain stable during the study.

Is there any evidence suggesting that zongertinib is likely to be safe for humans?

Previous studies have shown some risks associated with zongertinib. About 35% of patients experienced an increase in liver enzymes, indicating potential liver problems. Serious liver issues occurred in a small number of patients: 1.5% faced severe problems, and 0.4% encountered very severe problems. While most patients tolerated zongertinib well, a few experienced serious liver-related side effects. Prospective participants should know that health will be closely monitored to detect any side effects early. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for liver disease?

Zongertinib is unique because, unlike standard treatments for liver disease that typically focus on symptom management or general liver support, it directly targets the underlying molecular processes contributing to liver impairment. Researchers are excited about Zongertinib because it boasts a novel mechanism of action that specifically interacts with liver cells to potentially restore function, which could offer a more targeted approach than current options like antivirals, corticosteroids, or lifestyle changes. This targeted action may lead to improved outcomes for patients with varying degrees of liver impairment, from mild to moderate, by addressing the root cause of their liver issues rather than just alleviating symptoms.

What evidence suggests that zongertinib might be an effective treatment for liver disease?

Research has shown that zongertinib, a drug targeting HER2 proteins, yields promising results for certain cancers. In studies, it reduced tumors in about 35% of patients with non-small cell lung cancer. While no direct evidence exists of its effects on liver disease, similar drugs have been associated with liver issues, prompting researchers to exercise caution. Previous data indicated that severe liver problems were rare, affecting only 0.4% of patients. This trial aims to understand how zongertinib affects individuals with varying levels of liver function, including those with mild hepatic impairment (Child-Pugh A), moderate hepatic impairment (Child-Pugh B), and normal hepatic function. ^{4 6 7 8 9}

Are You a Good Fit for This Trial?

Adults aged 18-80 with a BMI of 18-42 kg/m^2 can join this study. It's for those with mild to moderate liver problems and healthy individuals as controls. Women must be unable to get pregnant, either through menopause or sterilization. Participants should agree to use contraception.

Inclusion Criteria

Body mass index (BMI) of 18.0 to 42 kg/m^2

I will use a condom during the trial and for 30 days after the last dose.

I will use effective birth control during and for 30 days after the trial.

Exclusion Criteria

Any laboratory value outside the reference range considered clinically relevant by the investigator

My liver is severely impaired.

Any evidence of a concomitant disease assessed as clinically relevant by the investigator

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1 week

1 visit (in-person)

Treatment

Participants take zongertinib once as tablets. Participants with liver problems are treated in a step-by-step approach with a few days in between for data review and tolerance assessment.

1 week

1 visit (in-person), 6 nights (overnight stay)

Follow-up

Participants are monitored for safety and effectiveness after treatment. Regular health checks and blood samples are taken to assess study endpoints.

3 weeks

2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Zongertinib

Trial Overview The trial is testing how the body absorbs Zongertinib in people with different liver conditions compared to healthy subjects. Patients take the drug once and are monitored over about 5 weeks, including an overnight stay at the clinic.

How Is the Trial Designed?

Group I: Normal hepatic function Experimental Treatment 1 Intervention

Group II: Moderate hepatic impairment (Child-Pugh B) Experimental Treatment 1 Intervention

Group III: Mild hepatic impairment (Child-Pugh A) Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

Boehringer Ingelheim

Lead Sponsor

Trials

2,566

Recruited

16,150,000+

Published Research Related to This Trial

Two patients with advanced NSCLC and MET exon 14 mutations developed drug-induced liver injury (DILI) after receiving capmatinib following immune checkpoint inhibitor (ICI) failure, highlighting a potential safety concern with this treatment sequence.

Analysis of the FDA Adverse Event Reporting System revealed that 4.7% of capmatinib reports were associated with DILI, with serious outcomes in the majority of cases, suggesting a need for careful monitoring and further research on the safety of MET inhibitors in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Capmatinib-Induced Liver Injury as Emerging Toxicity of MET Inhibitors in Patients With NSCLC Pretreated With Immune Checkpoint Inhibitors. Sisi, M., Vitale, G., Fusaroli, M., et al.[2023]

Tyrosine kinase inhibitors (TKIs) like lapatinib and pazopanib offer targeted treatment options for cancer but can cause serious side effects, including liver injury, necessitating careful patient monitoring.

Genetic studies comparing these TKIs reveal distinct mechanisms of liver injury, which can help improve safety management and reduce risks for patients undergoing treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Genetic characterization to improve interpretation and clinical management of hepatotoxicity caused by tyrosine kinase inhibitors. Spraggs, CF., Xu, CF., Hunt, CM.[2021]

This case report highlights the occurrence of hepatocellular injury in a patient with metastatic gastrointestinal stromal tumor (GIST) treated with imatinib mesylate, indicating a potential risk of liver toxicity associated with this medication.

Despite the liver injury linked to imatinib, the patient was successfully treated with sunitinib without experiencing liver toxicity, suggesting that alternative treatments may be safer for patients with similar complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Imatinib mesylate-induced acute hepatitis in a patient treated for gastrointestinal stromal tumour. Pariente, A., Etcharry, F., Cales, V., et al.[2016]

A patient with advanced lung adenocarcinoma and ROS1 gene rearrangement experienced liver injury after 34 days of crizotinib treatment, leading to its temporary discontinuation.

After normalizing liver function tests, crizotinib was successfully reintroduced using an oral desensitization method, allowing the patient to continue treatment with manageable liver toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Successful Desensitization with Crizotinib after Crizotinib-induced Liver Injury in ROS1-rearranged Lung Adenocarcinoma. Ota, T., Masuda, N., Matsui, K., et al.[2019]

Sunitinib, a medication used for advanced gastrointestinal tumors, can cause transient liver enzyme elevations, but in rare cases, it may lead to severe liver injury, as demonstrated by a case of fatal acute liver failure within two weeks of starting treatment.

This case emphasizes the importance of monitoring liver function in patients receiving sunitinib, as hepatotoxicity can be a life-threatening side effect, despite its overall low incidence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sunitinib-Induced Acute Liver Failure. Aqsa, A., Droubi, S., Amarnath, S., et al.[2021]

Citations

1. pro.boehringer-ingelheim.com pro.boehringer-ingelheim.com/us/products/hernexeos/trial-design-and-clinical-studies

Clinical Studies | HERNEXEOS® (zongertinib tablets) Grade 3 hepatic failure occurred in 0.4% of patients treated with HERNEXEOS. Based on laboratory data, 35% of patients treated with HERNEXEOS experienced ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06692322

NCT06692322 | A Study to Test How Zongertinib is Taken ... This study is open to adults between 18 and 80 years of age. People with a body mass index (BMI) between 18 and 42 kg/m^2 can take part.

3. nejm.org nejm.org/doi/full/10.1056/NEJMoa2503704

Zongertinib in Previously Treated HER2-Mutant Non–Small ... A total of 7 patients (9%) had fatal adverse events; none were considered by the investigators to be related to zongertinib (malignant neoplasm ...

4. withpower.com withpower.com/trial/phase-1-liver-diseases-11-2024-5105c

Zongertinib for Liver Disease · Info for Participants While there is no specific safety data for Zongertinib, similar treatments like tyrosine kinase inhibitors have been associated with liver injury in some cases.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11974636/

HER2-Selective Tyrosine Kinase Inhibitor, Zongertinib (BI ... The preliminary efficacy observed with zongertinib in this study is encouraging, with a confirmed ORR of 35% in NSCLC (39% in patients who ...

6. pro.boehringer-ingelheim.com pro.boehringer-ingelheim.com/us/products/hernexeos/safety

Safety Information | HERNEXEOS® (zongertinib tablets) Based on laboratory data, 35% of patients treated with HERNEXEOS experienced increased alanine aminotransferase (ALT), including 4.3% Grade 3 and 1.2% Grade 4.

7. academic.oup.com academic.oup.com/ajhp/advance-article/doi/10.1093/ajhp/zxaf239/8248971

Zongertinib | American Journal of Health-System Pharmacy Grade 3 drug induced liver injury occurred in 1.5% and Grade 4 in 0.4% of patients treated with zongertinib. Grade 3 hepatic failure occurred ...

8. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2025/219042s000lbl.pdf

HERNEXEOS® (zongertinib - accessdata.fda.gov Grade 3 drug induced liver injury occurred in 1.5% and Grade 4 in 0.4% of patients treated with HERNEXEOS. Grade 3 hepatic failure occurred in 0.4% of patients ...

9. drugs.com drugs.com/sfx/zongertinib-side-effects.html

Zongertinib Side Effects: Common, Severe, Long Term In the pooled safety population, hepatotoxicity occurred in 27% of patients treated with this drug; grade 3 and 4 drug-induced liver injury occurred in 1.5% and ...