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.