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

32 Participants Needed

Trial Summary

What is the purpose of this trial?

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. Women can only participate if they cannot get pregnant. This study includes people with mild liver problems, people with moderate liver problems, and people without liver problems as a matching control. The purpose of this study is to find out how mild and moderate liver problems affect how the body handles a medicine called zongertinib. 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 the doctors to review the data and make sure the participants can tolerate the treatment. Participants may continue their regular treatment for their liver problems during the study. Participants are in the study for about 5 weeks. During this time, they visit the study site 4 times. This also includes an overnight stay for 6 nights. During study visits, the doctors regularly check participants' health and take note of any unwanted effects. To assess the study endpoints, the study staff regularly takes blood samples.

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.

What safety data exists for Zongertinib or similar treatments in humans?

While there is no specific safety data for Zongertinib, similar treatments like tyrosine kinase inhibitors have been associated with liver injury in some cases. It's important to monitor liver function regularly when using these types of medications. ^{1 2 3 4 5}

Eligibility Criteria

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

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Imatinib mesylate-induced acute hepatitis in a patient treated for gastrointestinal stromal tumour. [2016]

2. England pubmed.ncbi.nlm.nih.gov

Genetic characterization to improve interpretation and clinical management of hepatotoxicity caused by tyrosine kinase inhibitors. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

Capmatinib-Induced Liver Injury as Emerging Toxicity of MET Inhibitors in Patients With NSCLC Pretreated With Immune Checkpoint Inhibitors. [2023]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Sunitinib-Induced Acute Liver Failure. [2021]

5. Japan pubmed.ncbi.nlm.nih.gov

Successful Desensitization with Crizotinib after Crizotinib-induced Liver Injury in ROS1-rearranged Lung Adenocarcinoma. [2019]