Pharmacokinetic Study of Oral IXAZOMIB in Cancer Patients With Liver Dysfunction

Inclusion Criteria:

- 18 years or older

- Patients must have a diagnosis of an advanced malignant solid tumor or hematologic
malignancy for which standard, curative, or life-prolonging treatment does not exist
or is no longer effective

- Total bilirubin and aspartate aminotransferase (AST) levels consistent with normal
hepatic function (total bilirubin and AST ≤ the upper limit of normal), moderate
hepatic impairment (total bilirubin > 1.5 to 3x the upper limit of normal with any
AST level) or severe hepatic impairment (total bilirubin > 3x the upper limit of
normal with any AST level)

- Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1

- Female patients who are postmenopausal for at least 1 year OR are surgically sterile
OR if of childbearing potential, agree to practice 2 effective methods of
contraception at the same time during the entire study through 90 days after the last
dose of study drug OR agree to practice true abstinence

- Male patients who agree to practice effective barrier contraception during the entire
study and through 90 days after the last dose of study drug OR agree to practice true
abstinence

- Voluntary written consent

- Suitable venous access for the conduct of blood sampling

- Appropriate clinical laboratory values as specified in the protocol

Exclusion Criteria:

- Systemic treatment with strong and moderate inhibitors of CYP1A2, strong and moderate
inhibitors of CYP3A, or clinically significant CYP3A inducers or use of Ginkgo biloba
or St. John's wort within 14 days before the first dose of study drug

- Use of any nicotine-containing products within 14 days before the first dose of study
drug

- Central Nervous System Involvement or Symptomatic brain metastasis. Patients with
brain metastases: must have stable neurologic status following local therapy (surgery
or radiation) for at least 2 weeks after completion of the definitive therapy; and
must be without neurologic dysfunction that would confound the evaluation of
neurologic and other AEs

- Female patients who are lactating or breastfeeding or have a positive serum pregnancy
test

- Serious medical or psychiatric illness that could interfere with participation in the
study

- Treatment with any investigational products or radiotherapy within 21 days before the
first dose of study drug

- Systemic anticancer therapy within 14 days before the first dose of study drug

- Exposure to nitrosoureas or mitomycin C within 6 weeks before the first dose of study
drug

- Treatment with therapeutic monoclonal antibodies or antibody-drug conjugates within
60 days before the first dose of study drug

- Radiotherapy or major surgery within the 14 days preceding the first dose of study
drug

- Infection requiring systemic intravenous antibiotic therapy or other serious
infection within 14 days before the first dose of study drug

- Life-threatening illness unrelated to cancer

- Severe CNS, pulmonary, or renal disease not related to the patient's cancer

- Known human immunodeficiency virus (HIV) positive

- Evidence of uncontrolled cardiovascular conditions

- QTc > 500 milliseconds (msec) on a 12-lead ECG obtained during the Screening period

- Known GI disease or GI procedure that could interfere with the oral absorption or
tolerance of IXAZOMIB

- Known allergy to the study medication, its analogues, or excipients in the
formulation