This study is being done to look at how tucatinib could affect the way other drugs work. This study will look at healthy volunteers and how tucatinib affects their liver enzymes. Liver enzymes can change how drugs work in the body. There are 5 parts to this study. Parts A and C are looking at how the body breaks down tucatinib when there are lower levels of certain liver enzymes. Part B is looking at how the body breaks down tucatinib when there are high levels of certain liver and stomach enzymes. Parts D and E are looking at how tucatinib could change the levels of some liver and stomach enzymes in the body. This will help us know more about how tucatinib should be given to patients.

This is a fixed-sequence, drug-drug interaction study of tucatinib conducted in 5 parts in healthy subjects. Part A will evaluate the effect of the strong CYP3A4 inhibitor itraconazole on the pharmacokinetics (PK) of tucatinib. Part B will evaluate the effect of rifampin, a strong inducer of CYP3A4 and CYP2C8, on the PK of tucatinib. Part C will evaluate the effect of the strong CYP2C8 inhibitor gemfibrozil on the PK of tucatinib. Part D will evaluate the effects of tucatinib on the PK of substrate probes of the metabolizing enzymes CYP2C8 (repaglinide), CYP2C9 (tolbutamide), and CYP3A4 (midazolam). Part E will evaluate the effect of tucatinib on the PK of a substrate probe of the transporter P-gp (digoxin). Parts A, B, C, D, and E of the study are independent of one another and do not need to be conducted in a particular order.

Inclusion Criteria:

• Body mass index (BMI) between 18 and 32 kg/m^2
• In good health, determined be no clinically significant findings from medical history, physical examination, and screening evaluations
• Female subjects must be of nonchildbearing potential
• Male subjects must agree to use contraception or must be surgically sterile for at least 90 days prior to enrollment
• Able to understand and sign informed consent form

Exclusion Criteria:

• Any condition affecting drug absorption (including stomach or intestinal surgery)
• Significant history of metabolic, allergic, dermatological, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, neurological, respiratory, endocrine, or psychiatric disorder
• History of hypersensitivity, intolerance, or allergy to any drug compounds, food, or other substance (unless approved by Investigator)
• Participation in a clinical study involving an investigational drug within the past 30 days
• Use or intend to any prescription medications within 28 days prior to check in
• Use of tobacco- or nicotine-containing products within 28 days prior to check in
• History of hyperbilirubinemia
• History of alcoholism or drug abuse within 2 years
• History of regular alcohol consumption exceeding 7 drinks/week for female subjects or 14 drinks/week for male subjects
• Positive hepatitis panel and/or positive human immunodeficiency virus (HIV) test