Zongertinib for Liver Disease

Recruiting in Palo Alto (17 mi)

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: Boehringer Ingelheim

Disqualifiers: Severe hepatic impairment, Severe renal, others

No Placebo Group

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 am between 18 and 80 years old.

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

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

Trial 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 (Tyrosine Kinase Inhibitor)

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

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

American Research Corporation at the Texas Liver Institute San Antonio, TX

Who Is Running the Clinical Trial?

Boehringer Ingelheim Lead Sponsor

References

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

Imatinib mesylate-induced acute hepatitis in a patient treated for gastrointestinal stromal tumour. [2016] We report the first case of hepatocellular injury occurring in a patient treated for metastatic gastrointestinal stromal tumour (GIST) with imatinib mesylate, with two positive rechallenges including one with 2.5% of the current therapeutic dosage. The patient could be treated later with sunitinib without liver toxicity. Grade 3-4 liver toxicity could occur in one out of 40 treated patients with imatinib for GIST, and fatalities have been reported. Regular monitoring of liver function tests is essential in patients treated with imatinib.

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

Genetic characterization to improve interpretation and clinical management of hepatotoxicity caused by tyrosine kinase inhibitors. [2021] Tyrosine kinase inhibitors (TKIs) represent important therapeutic alternatives to, or combinations with, traditional cytotoxic chemotherapy. Despite their selective molecular targeting and demonstrated clinical benefit, TKIs produce a range of serious adverse events, including drug-induced liver injury, that require careful patient management to maintain treatment benefit without harm. Genetic characterization of serious adverse events can identify mechanisms of injury and improve safety risk management. This review presents pharmacogenetic comparisons of two approved TKIs, lapatinib and pazopanib, which reveal different mechanisms of injury and inform the characteristics and risk of serious liver injury in treated patients. The data presented demonstrate the utility of genetic studies to investigate drug-induced liver injury and potentially support its management in patients.

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] Safety data on MET inhibitors in patients with advanced NSCLC harboring MET exon 14 mutation and treated with frontline immune checkpoint inhibitors (ICIs) are still limited. Here, we describe clinical characteristics, liver biopsy features, and management of liver injury of two patients with a diagnosis of MET exon 14-mutant NSCLC receiving capmatinib after ICI failure. On the basis of histologic findings and exclusion of other potential causes, a diagnosis of drug-induced liver injury (DILI) associated with portal fibrosis was made in both cases. The use of hepatoprotective drugs, in addition to oral ursodeoxycholic acid, resulted in liver blood tests normalization. To provide a global safety perspective, we queried the Food and Drug Administration Adverse Event Reporting System and detected a robust disproportionality signal. Out of the 918 total reports with capmatinib from the Food and Drug Administration Adverse Event Reporting System database, DILI was recorded in 43 cases (4.7%), mostly serious (93.0%) with hospitalization and death recorded in 25.6% and 16.3% of the cases, respectively. The median time to onset was 42 days, with discontinuation and positive dechallenge documented in 41.9% and 39.5% of the cases, respectively. Anti-programmed cell death protein-1 agents were coreported in 11 DILI cases. Only two cases of DILI out of 105 reports were found for tepotinib. Our data support a potential association between capmatinib and DILI in patients who have also been previously exposed to immunotherapy. Considering the potential implications for sequence strategy and timing of ICI and MET inhibitor, further investigation is warranted.

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

Sunitinib-Induced Acute Liver Failure. [2021] Drug-induced liver injury is an uncommon but life-threatening entity. Sunitinib is a tyrosine kinase inhibitor used for advanced and imatinib-refractory gastrointestinal stromal tumors. It causes transient elevation in liver enzymes. The incidence of fatal acute liver failure is rare. Five cases of sunitinib-induced acute liver injury have been reported in the literature thus far. We present a case of fatal acute liver failure and cardiomyopathy within 2 weeks of sunitinib therapy initiation for advanced pancreatic neuroendocrine carcinoma. We believe our case is unique due to the rarity of its presentation. It highlights hepatotoxicity as a potentially fatal side effect of sunitinib therapy.

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

Successful Desensitization with Crizotinib after Crizotinib-induced Liver Injury in ROS1-rearranged Lung Adenocarcinoma. [2019] Crizotinib has been approved for patients with advanced lung adenocarcinoma harboring rearrangements of the c-ROS-1 (ROS1) and anaplastic lymphoma kinase (ALK) genes. We report a patient with ROS1-rearranged lung adenocarcinoma who developed a crizotinib-induced mixed/cholestatic type of liver injury. The patient discontinued crizotinib after 34 days due to liver toxicity. Twenty-four days later, when transaminases and C reactive protein (CRP) were normalized, crizotinib was resumed using an oral desensitization method. The patient was successfully treated for manageable recurrence of liver injury and has been able to continue the treatment.