Efficacy/Safety of Imprime PGG® Injection With Bevacizumab and Paclitaxel/Carboplatin in Patients With Untreated Advanced Non-Small Cell Lung Cancer (NSCLC)

Inclusion criteria

• Has read, understood and signed the informed consent form (ICF) approved by the Independent Review Board/Ethics Committee (IRB/EC);
• Is between the ages of 18 and 75 years old, inclusive;
• Has histologically or cytologically confirmed stage IIIB (malignant pericardial or pleural effusion) or stage IV non-small cell lung cancer;
• Has non-squamous, non-small cell lung cancer
• Has measurable disease, defined as at least one tumor that fulfills the criteria for a target lesion according to RECIST;
• Has an ECOG performance status of 0 or 1;
• Has a life expectancy of > 3 months;
• Has adequate hematologic function as evidenced by:

• ANC ≥ 1,500/μL
• PLT ≥ 100,000/μL
• HGB ≥ 9 g/dL obtained within 1 week prior to the first dose of study medication;
• Has adequate renal function as evidenced by:

• Serum creatinine ≤ 1.5 X the upper limit of normal (ULN) for the reference lab
• Urine dipstick for proteinuria of < 1+ (i.e., either 0 or trace) within 2 weeks of Day 1 If urine dipstick is ≥ 1+, then urine protein excretion must be ≤ 500 mg over a 24 hour collection obtained within 1 week prior to the first dose of study medication;
• Has adequate hepatic function as evidenced by:

• Serum total bilirubin ≤ 1.0 mg/dL
• AST ≤ 2.5X ULN for the reference lab (≤ 5X ULN for subjects with known hepatic metastases)
• ALT ≤ 2.5X ULN for the reference lab (≤ 5X ULN for subjects with known hepatic metastases) obtained within 1 week prior to the first dose of study medication;
• Has adequate coagulation function as evidenced by:

• INR ≤ 1.5
• PTT ≤ ULN for the reference lab obtained within 1 week prior to the first dose of study medication;
• If a woman of childbearing potential or a fertile man (and his partners), must agree to use an effective form of contraception (hormonal contraceptive, double-barrier method or abstinence) during the study.

Exclusion criteria

• Has received prior systemic chemotherapy at any time for lung cancer;
• Has received previous radiation therapy to >30% of active bone marrow or any radiation therapy within 3 weeks of Day 1;
• Has a known hypersensitivity to baker's yeast, or has an active yeast infection;
• Has had previous exposure to Betafectin® or Imprime PGG;
• Has an active infection;
• Presents with any of the following medical diagnoses/conditions at the time of screening:

• Central nervous system (CNS) metastases
• Uncontrolled hypertension (>150/100 mmHg) or hypertension that requires > two agents for adequate control
• Peripheral neuropathy ≥ grade 2 from any cause
• Fever of >38.5° C within 3 days prior to screening or Day 1, initial dosing
• Known HIV/AIDs, Hepatitis B, Hepatitis C, connective tissue or autoimmune disease, or other clinical diagnosis, ongoing or intercurrent illness that in the physician's opinion could interfere with participation
• Has a history of any of the following medical diagnoses/conditions:

• Arterial or venous thromboembolic or hemorrhagic disorders including stroke, transient ischemic attack or cerebral infarction
• Deep vein thrombosis within 1 year prior to screening
• Myocardial infarction or an unstable or uncontrolled disease or condition related to or impacting cardiac function (e.g., unstable angina, congestive heart failure) within the previous 6 months
• Second malignancy within the previous 5 years, other than basal cell carcinoma, cervical intra-epithelial neoplasia or curatively treated prostate cancer with a PSA of <2.0 ng/mL
• Has a known hypersensitivity to bevacizumab, murine proteins, or any component of bevacizumab;
• Has a know sensitivity to polyethoxylated castor oil;
• Has previously received treatment with bevacizumab;
• Has had surgery within 4 weeks of Day 1 or needle or open biopsy within 1 week of Day 1;
• Has a non-healing wound or gastric ulcer;
• Has a non-healed bone fracture;
• Is receiving systemic anti-coagulation therapy (e.g., dipyridalmole (Persantine®), ticlopidine (Ticlid®), clopidogrel (Plavix®) and /or cilostazol (Pletal®);
• Is receiving chronic daily treatment with aspirin (>100 mg/day) or other nonsteroidal anti-inflammatory agents known to inhibit platelet function within 1 week of Day 1;
• Presents with any of the following medical diagnoses/conditions at the time of screening:

a. Predominant squamous cell histology

• Has a history of any of the following medical diagnoses/conditions:

• Hemoptysis (≥ ½ tsp red blood)
• Bleeding diathesis or coagulopathy
• If female, is pregnant or breast-feeding;
• Is receiving concurrent investigational therapy or has received investigational therapy within a period of 30 days prior to the first scheduled day of dosing (investigational therapy is defined as treatment for which there is currently no regulatory-authority-approved indication);
• Has previously received an organ or progenitor/stem cell transplant.