| Inclusion Criteria: | 1) a. For Subjects Treated in the Dose Escalation Portion of Part A: Subjects have a histologically or cytologically confirmed solid tumor that is metastatic or unresectable and refractory to standard therapy, or for which no known effective therapy exists. (NOTE: Subjects who are ineligible for or have refused treatment with standard therapies may be enrolled with sponsor agreement.) (continued below).
2) Continued from 1) b. For Subjects Treated in the Cohort Expansion Portion of Part A: Subjects have either (1) advanced or recurrent platinum-refractory or platinum-resistant epithelial ovarian carcinoma, including fallopian tube and primary peritoneal cancer, which has been previously treated with a taxane (see NOTE) or (2) advanced or recurrent ovarian endometrial carcinoma (endometrioid, serous, clear cell adenocarcinoma, adenosquamous carcinoma, or mixed histology, any grade.) ( continued below).
3) (continued from above) There are no requirements or restriction for treatments with prior chemotherapy regimens for subjects with endometrial cancer. NOTE: Platinum refractory is defined as progressive disease during a platinum-based chemotherapy. Platinum resistant is defined as disease that has recurred within 6 months of receiving the last platinum-based chemotherapy.c. For All Subjects in Part B: Subjects have unresectable (Stage IIIB or IV) NSCLC. NOTE: For subjects with Stage IIIB or IV NSCLC, no requirements or restrictions for treatments with prior chemotherapy regimens apply.
4) For All Subjects Treated in the Cohort Expansion Portion of Either Part A or Part B: At least 10 unstained slides of tumor tissue, archival or fresh, or a paraffin block or a fresh tumor biopsy must be identified and designated for central laboratory analysis.
5) The subject has measurable or non-measurable lesions by the Response Evaluation Criteria in Solid Tumors (RECIST) criteria.
6) The subject has recovered from the adverse effects of prior therapy at the time of enrollment to ≤ Grade 1 (excluding alopecia).
7) The subject is age >/= 18 years.
8) The subject's weight is >/= 40 kg.
9) The subject has an Eastern Cooperative Oncology Group (ECOG) performance status </= 1 (subjects with performance status 2 may be considered following discussion and agreement with the sponsor).
10) The subject has adequate organ and marrow function, as defined by the following parameters: a. absolute neutrophil count (ANC) >/= 1500/mm3 b. platelets >/= 100,000/mm3 c. hemoglobin >/= 9 g/dL d. total bilirubin </= 1.5 × the upper limit of normal (ULN) e. serum creatinine </= 1.5 × ULN or calculated creatinine clearance >/= 60 mL/min f. For subjects without liver metastases: AST and ALT levels </= 2.5 × ULN
11) The subject has a fasting plasma glucose </= 160 mg/dL.
12) The subject is capable of understanding and complying with the protocol requirements and will sign and date the IRB-approved informed consent document prior to any protocol-specific screening procedures being performed.
13) For female subjects of childbearing potential, a negative serum pregnancy test result is documented at screening. Females of childbearing potential are defined as sexually mature women without prior hysterectomy or who have had any evidence of menses in the past 12 months. However, women who have been amenorrheic for 12 or more months are still considered to be of childbearing potential if the amenorrhea is possibly due to prior chemotherapy, anti-estrogens, or ovarian suppression.
14) Female subjects of child-bearing potential and male subjects whose sexual partners are women of childbearing potential agree to use acceptable methods of conception during the course of the study and for 3 months after the last dose of study treatment. |