Study of Orally Administered TAK-960 in Patients With Advanced Nonhematologic Malignancies

A Phase 1, Open-Label, Dose-Escalation Study of Orally Administered TAK-960, a Polo-Like Kinase 1 Inhibitor, in Patients With Advanced Nonhematologic Malignancies

Overview of Study Design: This is a phase 1, multicenter, open-label, multiple-dose, dose-escalation study designed to evaluate the safety, tolerability, pharmacokinetics (PK), and antitumor activity of TAK-960 in patients with advanced nonhematologic malignancies. This study will be the first to administer TAK-960 to humans. The patient population will consist of adults with a nonhematologic malignancy for which standard treatment is no longer effective or does not offer curative or life-prolonging potential, or for which no standard treatment is available.

Inclusion Criteria:

Each patient must meet all of the following inclusion criteria to be enrolled in the study:

• Male or female 18 years or older
• Clinical laboratory values as specified in protocol
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Histologically and/or cytologically confirmed diagnosis of metastatic, unresectable, advanced evaluable nonhematologic malignancy for which standard treatment is not available or no longer effective
• Radiographically or clinically evaluable tumor
• Suitable venous access for study-required blood sampling
• Female patients who are postmenopausal, surgically sterile or agree to practice 2 effective methods of contraception or abstain from heterosexual intercourse
• Male patients who agree to practice effective barrier contraception or agree to abstain from heterosexual intercourse
• Voluntary written consent
• Willing to undergo biopsy procedures (expansion phase only)
• Weight at least 40 kg
• Recovered from the reversible effects of prior antineoplastic therapy to Grade ≤ 1 or to patient's baseline values, excluding alopecia

Exclusion Criteria:

Patients meeting any of the following exclusion criteria are not to be enrolled in the study:

• Diagnosis of primary central nervous system malignancy or carcinomatous meningitis
• Patient has symptomatic brain metastasis. Patients with brain metastases must: have stable neurologic status for at least 2 weeks following completion of local therapy AND be without neurologic dysfunction that would confound the evaluation of adverse events
• Prior allogeneic bone marrow or stem cell transplant
• Prior therapy or treatment as specified in protocol
• Female patients who are lactating or who have a positive serum pregnancy test during the screening period of within 3 days before the first dose of TAK-960
• Myocardial infarction within 6 months before first dose of TAK-960
• Any of the cardiovascular conditions or values as specified in the study protocol within 6 months before the first dose of TAK-960
• Infection requiring systemic anti-infective therapy within 14 days before the start of TAK-960, or other severe infection
• Known human immunodeficiency virus (HIV) positive, hepatitis B surface antigen-positive or known suspected active hepatitis C infection
• A diagnosis of or treated for another malignancy within 2 years before the first dose of TAK-960 or previous diagnosis of another malignancy and any evidence of residual disease. Patients with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection
• Any serious medical or psychiatric illness that could potentially interfere with the completion of treatment
• Recurrent nausea or vomiting or requirement for antiemetic therapy within 14 days before the first dose of TAK-960
• Known gastrointestinal (GI) disease or GI procedure that could interfere with the oral absorption or tolerability of TAK-960, including difficulty swallowing capsules
• Treatment with any investigational products within 21 days before the first dose of TAK-960
• Systemic use of strong CYP3A inhibitors or inducers within 14 days before the first dose of TAK-960
• Patients enrolled in the expansion cohorts where tumor biopsies are required must meet additional criteria according to the study protocol