Phase I Study of TAK-701 in Adult Patients With Advanced Nonhematological Malignancies

Inclusion criteria

• Male or female patients aged 18 years or older.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
• Diagnosis of a nonhematologic malignancy for which standard curative or lifeprolonging treatment does not exist or is no longer effective.
• Radiographically or clinically evaluable tumor; however, measurable disease is not required for participation in this study (eg, patients with pleural effusion or ascites).
• Female patients who:

• Are postmenopausal for at least 1 year before the screening visit, or
• Are surgically sterile, or
• If they are of childbearing potential, agree to practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent form through 3 months after the last dose of study drug, or agree to completely abstain from heterosexual intercourse.

Male patients, even if surgically sterilized (ie, status postvasectomy), who:

• Agree to practice effective barrier contraception during the entire study drug treatment period and through 3 months after the last dose of TAK-701, or
• Agree to completely abstain from heterosexual intercourse.
• Voluntary written consent must be given before performance of any study-related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care.

Exclusion criteria

• Female patients who are lactating or have a positive serum pregnancy test during the screening period.
• Major surgery within 14 days before the first dose of TAK-701 or any planned/anticipated surgery during the study period.
• Positive test for Hepatitis B or C infection.
• Active alcohol abuse
• Active infection requiring systemic therapy, or other serious infection.
• Antineoplastic therapy (including unconjugated therapeutic antibodies and toxin immunoconjugates) or any experimental therapy within 21 days before the first dose of TAK-701.
• Radiotherapy within 21 days before the first dose of TAK-701.
• Nitrosoureas or mitomycin-C within 6 weeks before the first dose of TAK-701.
• Autologous stem cell transplant within 3 months before the first dose of TAK-701, or prior allogeneic stem cell transplant at any time.
• Any prior exposure to anti-HGF therapy (eg, AMG-102, AV-299).
• The patient has symptomatic brain metastasis.
• Absolute neutrophil count < 1,500/mm3; platelet count < 100,000/mm3.
• Calculated creatinine clearance < 50mL/minute
• Any of the following clinical laboratory results during screening (ie, within 28 days before the first dose of TAK-701):

• Bilirubin > 1.5 times the upper limit of the normal range (ULN).
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2.5 times the ULN. AST and ALT may be elevated up to 5 times the ULN if their elevation can be reasonably ascribed to the presence of metastatic disease to liver and/or to bone.
• Known human immunodeficiency virus (HIV) positive.
• Serious medical or psychiatric illness likely to interfere with participation in this clinical study.
• Uncontrolled cardiovascular condition, including ongoing cardiac arrhythmias, congestive heart failure, angina, or myocardial infarction within the past 6 months.
• Patients having QTc > 470 msec on a 12-lead ECG obtained within 28 days before first study drug administration.
• Presence of serious or nonhealing wound, ulcer or bone fracture.