Inclusion Criteria:

- Histologically or cytologically confirmed metastatic or unresectable malignancy

- Measurable disease (RECIST version 1.1.)

- Prior therapies

- ALL: No prior PI3K-Akt-mTOR inhibitors

- Dose escalation cohorts: No limits

- Dose expansion (up to n=12 each ):

- Uterine: At least 1 prior chemo required. Hormones allowed

- Renal: At least one anti-VEGF/R treatment (Rx) required.

- Carcinoid: Long-acting somatostatin analogue allowed. Prior regional Rx for
liver mets allowed. Prior anti-VEGF/R Rx allowed

- Age ≥ 18

- ECOG 0-1

- Life expectancy ≥ 12 weeks

- Well controlled blood pressure (BP): ≤140/90 mmHg (anti-hypertension meds allowed)

- Normal organ function

- leukocytes ≥3.0 x 109/L

- absolute neutrophil count ≥1.5 x 109/L

- platelets ≥100 x 109/L

- hemoglobin > 90 g/L (or > 9 g/dL)

- total bilirubin ≤ institutional ULN

- AST(SGOT)/ALT(SGPT)≤2.5 X institutional upper limit of normal if no known liver
metastasis or ≤5 X institutional upper limit of normal if known liver metastasis

- PTT or aPTT ≤1.5 X ULN per institutional laboratory range and INR ≤1.5

- creatinine ≤ institutional ULN OR >40 mL/min per 24 h urine collection or
calculated according to the Cockcroft-Gault formula

- urinary protein ≤30 mg/dL in urinalysis or ≤1+ on dipstick, unless quantitative
protein is <1000 mg in a 24 h urine sample

Exclusion Criteria:

- History of CNS metastases

- History of arterial or venous thromboembolism ≤ 12 months

- Therapeutic anticoagulation (neither with LMWH nor warfarin)

- Clinically significant bleeding ≤ 6 months

- Clinically significant cardiovascular disease

- Major surgery ≤ 28 days

- Current of previous treatment with AMG 386 or other angiopoietins or TIE2 receptor
inhibitors

- Minor surgery ≤ 3 days (7 days if prior VEGF inhibitor)

- Prior (≤ 4 weeks) chemo- or radiotherapy

- Prior treatment (≤ 30 days) with immunomodulators

- Patients who have not yet completed prior Rx at least 21 days (30 days prior for
mAbs)

- Non-healing wound, ulcer, fracture

- Uncontrolled intercurrent illness

- Pregnant women/subjects not consenting for double-barrier contraception

- Not recovery from prior Grade ≥2 toxicities (NCI CTC v4.0)

- Strong inducers or inhibitors of CYP3A4

- Pre-existing clinically significant pulmonary infiltrates

- Patients with an indwelling peritoneal or pleural catheter that is used to manage
malignant effusions.

- Known intra-abdominal inflammatory process or serious gastrointestinal ulceration.

- No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within
the past 6 months

- No gastric or esophageal varices

- Patients with primary bowel tumors in situ or recurrent disease at bowel anastomosis