A Study of MNRP1685A in Combination With Bevacizumab With or Without Paclitaxel in Patients With Locally Advanced or Metastatic Solid Tumors

Inclusion Criteria:

• Adequate hematologic and end organ function
• Evaluable disease or measurable disease per Response Evaluation Criteria In Solid Tumors (RECIST)
• Agreement to use an effective form of contraception for the duration of the study

Inclusion Criteria Unique to Arm A:

• Histologically or cytologically documented, incurable, locally advanced, or metastatic solid malignancy that has progressed on, or failed to respond to, at least one prior regimen

Inclusion Criteria Unique to Arm B:

• Histologically or cytologically documented, incurable, locally advanced, or metastatic solid malignancy; a maximum of two prior chemotherapy regimens is allowed

Exclusion Criteria:

• Any anti-cancer therapy, including chemotherapy, hormonal therapy, or radiotherapy, within 3 weeks or 5 half-lives (for systemic agents), whichever is shorter, prior to initiation of study treatment with the following exceptions: hormonal therapy with gonadotropin-releasing hormone (GnRH) agonists or antagonists for prostate cancer; herbal therapy > 1 week prior to Day 1; hormone-replacement therapy or oral contraceptives; palliative radiotherapy for bone metastases > 2 weeks prior to Day 1
• Any condition requiring full-dose anticoagulants, such as warfarin, heparin, or thrombolytics, or a filter of the inferior vena cava
• Leptomeningeal disease as a manifestation of the current malignancy
• Active infection requiring IV antibiotics
• Active autoimmune disease that is not controlled by nonsteroidal anti-inflammatory drugs, inhaled corticosteroids, or the equivalent of ≤ 10 mg/day prednisone
• Bisphosphonate therapy for symptomatic hypercalcemia
• Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis, or cirrhosis
• Known human immunodeficiency virus (HIV) infection
• Known primary CNS malignancy, or untreated or active CNS metastases
• Pregnancy, lactation or breast feeding
• Inadequately controlled hypertension
• History of hypertensive crisis or hypertensive encephalopathy
• History of myocardial infarction or unstable angina within 6 months prior to Day 1
• New York Heart Association (NYHA) Class II or greater CHF
• History of stroke or transient ischemic attack (TIA) within 6 months prior to Day 1
• Significant vascular disease (e.g., aortic aneurysm requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to Day 1
• History of hemoptysis within 1 month prior to Day 1
• Evidence of bleeding diathesis or significant coagulopathy in the absence of stable therapeutic anticoagulation
• Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 1 or anticipation of need for major surgical procedure during the course of the study
• Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to Day 1
• History of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 6 months prior to Day 1
• Clinical signs or symptoms of gastrointestinal obstruction or requirement for parenteral hydration, parenteral nutrition, or tube feeding because of an active gastrointestinal condition
• Evidence of abdominal free air not explained by paracentesis or recent surgical procedure
• Serious, non-healing wound, active gastrointestinal ulcer, or untreated bone fracture
• Intrathoracic lung carcinoma of squamous cell histology
• Grade ≥ 2 sensory neuropathy
• Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that, in the investigator's opinion, gives reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the patient at high risk from treatment complications
• Known hypersensitivity to recombinant human antibodies

Exclusion Criterion Unique to Arm B:

• Known significant hypersensitivity to paclitaxel or other drugs using the vehicle cremophor