Study of TAK-733 in Adult Patients With Advanced Nonhematologic Malignancies

Inclusion Criteria:

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

- 18 years or older.

- Have one of the following diagnoses: a nonhematologic malignancy for which standard,
curative, or life-prolonging treatment does not exist or is no longer effective; OR
have stage 3 or stage 4 unresectable melanoma not priorly treated with either MEK or
BRAF inhibitor therapy.

- Melanoma patients should have the V600E BRAF mutation status of their tumor
documented, if available, and tumor tissue must be provided for confirmatory
genotyping by a central laboratory.

- Have a radiographically or clinically evaluable tumor.

- Have suitable venous access for the conduct of blood sampling.

- Provide voluntary written consent, which can be withdrawn by the patient at any time.

- Female patients who: are post-menopausal for at least 1 year before screening; OR are
surgically sterile; OR if they are of childbearing potential agree to practice two
effective methods of birth control from the time of signing the informed consent form
through 30 days after the last dose of the study drug, or agree to completely abstain
from heterosexual intercourse.

- Male patients, even if surgically sterilized, must agree to practice effective
barrier contraception during the entire study treatment period and through 30 days
after the last dose of the study drug; OR agree to completely abstain from
heterosexual intercourse.

Exclusion Criteria:

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

- Female patients who are lactating or have a positive serum pregnancy test during the
Screening period.

- Antineoplastic therapy or radiotherapy within 21 days; or nitrosoureas of mitomycin C
within 42 days

- Prior biologic or immunotherapy ≤ 4 weeks prior to enrollment.

- Grade 2 or greater unresolved toxicity (except alopecia) from previous anticancer
therapy.

- Major surgery within 14 days of the first dose of the study drug.

- An active infection requiring systemic therapy; or other severe infection.

- Symptomatic brain metastases.

- Inability to meet specific laboratory test standards during the Screening period as
specified in the study protocol.

- Human Immunodeficiency (HIV) positive.

- Hepatitis B surface antigen positive or active hepatitis C infection.

- Serious medical or psychiatric illness likely to interfere with the study.

- Uncontrolled cardiovascular condition.

- Abnormalities on 12-lead ECG performed within 28 days before the start of the study
drug that are considered to be clinically significant or rate corrected QT interval >
470 milliseconds.

- Melanoma patients will be excluded if they have had a diagnosis with or treatment for
another malignancy within 2 years of the first dose of the study drug, or have been
previously diagnosed with another malignancy with any evidence of residual disease.

- Treatment with any investigational product within 28 days before the first dose of
the study drug.

- A history of an ongoing or newly diagnosed eye abnormality, such as retinal or
corneal pathologies.

- Abnormal left ventricular ejection fraction (LVEF).

- Receiving therapeutic anticoagulation

- Treatment with any of the following strong CYP3A inhibitors or inducers within 14
days before the first dose of study drug: ketoconazole, itraconazole, voriconazole,
posaconazole, clarithromycin, telithromycin, nefazodone, rifampin, rifapentine, or
rifabutin.