A Phase 1 Study of CC-486 as a Single Agent and in Combination With Carboplatin or ABI-007 in Subjects With Relapsed or Refractory Solid Tumors

Inclusion Criteria:

1. Men and women, 18 years or older at the time of signing the Informed Consent Document (ICD).
2. Understand and voluntarily sign an ICD prior to any study-related assessments or procedures are conducted.
3. Able to adhere to the study visit schedule and other protocol requirements.
4. With histological or cytological confirmation of advanced unresectable solid tumors, including those who have progressed on (or not been able to tolerate) standard anticancer therapy, or for whom no other effective therapy exists, or for who declines standard therapy.
5. Consent to screening tumor biopsy (for accessible tumors when appropriate [optional in Part 1, mandatory in Part 2]).
6. Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2.

7. The following laboratory values:

   • Absolute neutrophil count (ANC) ≥ 1.5 X 10^9/L
   • Hemoglobin (Hgb) ≥90 g/L
   • Platelets (plt) ≥ 100 x 10^9/L
   • Potassium within normal range, or correctable with supplements;
   • AST and ALT ≤2.5 x Upper Limit Normal (ULN) or ≤5.0 x ULN if liver tumor is present;
   • Serum total bilirubin ≤ 1.5 x ULN
   • Serum creatinine ≤ 1.5 x ULN, or 24-hr clearance ≥ 60ml/min; and
   • Negative serum pregnancy test within 7 days before starting study treatment in females of childbearing potential (FCBP)
8. Part 2 only: Measureable tumor (types to be determined during Part 1)

9. Females of child-bearing potential {defined as a sexually mature women who

   • has not undergone a hysterectomy (the surgical removal of the uterus) or bilateral oophorectomy (the surgical removal of both ovaries) or,

   • has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time during the preceding 24 consecutive months} must

     • agree to the use of a physician- approved contraceptive method (oral, injectable, or implantable hormonal contraceptive ; tubal ligation; intra-uterine device; barrier contraceptive with spermicide; or vasectomized partner) while on oral azacitidine and for 3 months following the last dose of study medication; and
     • have a negative serum pregnancy test during screening
10. Male subjects with female partner of childbearing potential must agree to the use of a physician-approved contraceptive method throughout the course of the study to avoid fathering a child during the course of the study and for 6 months following the last dose of oral azacitidine.

Exclusion Criteria:

1. Any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study.
2. Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study.
3. Any condition that confounds the ability to interpret data from the study.
4. Symptomatic central nervous system metastases. Subjects with brain metastases that have been previously treated and are stable for 6 weeks are allowed.
5. Known acute or chronic pancreatitis.
6. Any peripheral neuropathy ≥ NCI CTCAE grade 2.
7. Persistent diarrhea or malabsorption ≥ NCI CTCAE grade 2, despite medical management.
8. Impaired ability to swallow oral medication.
9. Unstable angina, significant cardiac arrythmia, or New York Heart Association (NYHA) class 3 or 4 congestive heart failure.
10. Prior systemic cancer-directed treatments or investigational modalities ≤ 5 half lives or 4 weeks, whichever is shorter, prior to starting study drug or who have not recovered from side effects of such therapy. (except alopecia).
11. Major surgery ≤ 2 weeks prior to starting a study drug or who have not recovered from side effects of such therapy.
12. Pregnant or breast feeding.
13. Known Human Immunodeficiency Virus (HIV) infection.
14. Known chronic hepatitis B or C virus (HBV/HCV) infection, unless this is a comorbidity in subjects with HCV.