Pembrolizumab (Anti-PD-1) and AMG386 (Angiopoietin-2 (Ang-2) in Patients With Advanced Solid Tumor

Inclusion Criteria

• Be willing and able to provide written informed consent for the trial.
• Be ≥ 18 years of age on day of signing informed consent.
• Have measurable disease based on RECIST 1.1.
• In dose escalation (Phase I), patients must have histologically or cytologically confirmed metastatic disease from any solid tumor that is incurable and fulfills one of the following criteria:
• Has demonstrated progression of disease following at least one line of effective systemic therapy. Prior treatment with anti-CTLA-4 antibody (including ipilimumab) is allowable OR
• For which effective therapy does not exist
• In dose expansion (part 2), patients must have histologically or cytologically confirmed unresectable or metastatic melanoma, renal cell carcinoma, ovarian cancer, or colorectal cancer.
• Renal cell patients must have had at least one prior VEGF TKI.
• Ovarian cancer patients must be resistant to platinum therapy (i.e. within 6 months of last platinum therapy).
• Patients with colorectal cancer should have progressed on at least one fluorouracil plus irinotecan or oxaliplatin containing regimen.
• Patients with melanoma should have unresectable or metastatic disease. Melanoma patients with BRAF V600E or V600K mutation-positive melanoma who have previously received a BRAF inhibitor with or without a MEK inhibitor) are eligible.
• In the dose expansion cohort patients should be willing to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion (pre-treatment) and post-treatment biopsy. Newly-obtained is defined as a specimen obtained up to 6 weeks (42 days) prior to initiation of treatment on Day 1. Patients for whom newly-obtained samples cannot be provided (e.g., inaccessible, subject safety concern, or unwilling to undergo biopsy) may submit an archived specimen only upon agreement from the Sponsor. An on-treatment biopsy will be collected approximately halfway through the induction period, about 6 weeks from the start of study treatment (sometime between Cycle 2 Day 8 - Cycle 3 Day 1).
• Have a performance status of 0 or 1 on the ECOG Performance Scale (see Appendix A) up to 28 days before treatment initiation
• Demonstrate adequate organ function as defined in Table 1, all screening labs should be performed up to 28 days before treatment initiation.
• System Laboratory Value
• Hematological
• Absolute neutrophil count (ANC) ≥1,500 /mcL
• Platelets ≥100,000 / mcL
• Hemoglobin ≥9 g/dL or ≥5.6 mmol/L without transfusion or EPO dependency (within 7 days of assessment)
• Renal

--Serum creatinine OR Measured or ≤1.5 X upper limit of normal (ULN) OR calculateda creatinine clearance ≥60 mL/min for subject with creatinine levels (GFR can also be used in place of > 1.5 X institutional ULN creatinine or CrCl)

• Hepatic
• Serum total bilirubin ≤ 1.5 X ULN OR Direct bilirubin ≤ ULN for subjects with total bilirubin levels > 1.5 ULN AST (SGOT) and ALT (SGPT) ≤ 2.5 X ULN OR ≤ 5 X ULN for subjects with liver metastases
• Albumin >2.5 mg/dL
• Coagulation
• International Normalized Ratio (INR) ≤1.5 X ULN unless subject is receiving therapy as or Prothrombin Time (PT) long as PT or PTT is within therapeutic range of intended use of anticoagulants
• Activated Partial Thromboplastin Time ≤1.5 X ULN unless subject is receiving (aPTT) anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
• Creatinine clearance should be calculated per institutional standard.
• Negative protein on screening urinalysis
• Female subject of childbearing potential should have a negative serum pregnancy test within 24 hours prior to receiving the first dose of study medication.
• Female subjects of childbearing potential (Section 5.11.2) must be willing to use an adequate method of contraception as outlined in Section 5.11.2 - Contraception, for the course of the study through 120 days after the last dose of study medication. Should a woman become pregnant or suspect she is pre