A Phase 1, Open-label, Single-dose Study to Assess the Influence of Hepatic Impairment on the Pharmacokinetics of BAY 2927088
This is a research study to understand how liver impairment affects the way the body processes a new cancer medicine called sevabertinib (BAY 2927088). Sevabertinib is an experimental drug being developed to treat certain types of cancers that have specific genetic changes called HER2 mutations. This includes lung cancer, tumors that have spread to other parts of the body (metastatic), and tumors that cannot be removed with surgery (unresectable). Before this medicine can be given to cancer patients with liver problems, researchers need to understand how liver disease might change the way the body handles the drug. The study will include about 20 people divided into two groups: 10 people with moderate liver problems (called Child-Pugh B liver impairment) and 10 healthy people with normal liver function. The healthy volunteers will be matched to the liver patients by age, sex, and weight to make fair comparisons. All participants will take a single 20 mg dose of sevabertinib by mouth and stay in the research clinic for 5 days. During this time, researchers will take blood samples at specific times to measure how much drug is in the blood and how long it stays in the body. They will also monitor participants closely for any side effects. The main goal is to see if people with liver problems have different drug levels in their blood compared to healthy people. This information will help doctors determine if cancer patients with liver disease need different doses of sevabertinib to be safe and effective. The study will also look at the safety and tolerability of sevabertinib in both groups. Participants will have follow-up visits to ensure their continued health and safety. This research is important because many cancer patients also have liver problems, and understanding how liver disease affects this new cancer treatment will help ensure it can be used safely and effectively in all patients who might benefit from it.
• Participant must be 18 to 79 years of age inclusive, at the time of signing the informed consent.
• Normal hepatic function or moderate hepatic impairment.
• Body weight of at least 50 kg and BMI of within the range 18 to 40 kg/m2 inclusive.
• Female, of non childbearing potential only. Females must not be pregnant or breastfeeding, and must be documented as of non-childbearing potential (WONCBP). A negative pregnancy test is required.
• Male study participants of reproductive potential must agree to use adequate contraception when sexually active from signing the Informed Consent Form (ICF) until at least 3 months after the last dose of study intervention, and refrain from sperm donation during study intervention and for 3 months after the last dose of study intervention.
• Signed ICF.
• Documented liver disease with findings consistent with cirrhosis confirmed by histopathology, laparoscopy, fibroscan, CT, MRI, or ultrasound, AND
• Hepatic impairment (Child-Pugh B), AND
• Stable liver disease (i.e., same Child-Pugh class for at least 2 months prior to screening).
• Have normal hepatic function, AND
• Fulfil Arm A matching criteria (sex, age, and body weight).