The Phase 2 study described in this protocol will serve to evaluate the antitumor activity, safety and pharmacokinetic profile of Imprime PGG when combined with bevacizumab and concomitant paclitaxel and carboplatin therapy in patients with previously untreated advanced NSCLC. Additionally, this study will provide guidance for the design of more definitive efficacy studies of Imprime PGG in NSCLC patients.

Inclusion Criteria:

1. Has read, understood and signed the informed consent form (ICF) approved by the Independent Review Board/Ethics Committee (IRB/EC);

2. Is between the ages of 18 and 75 years old, inclusive;

3. Has histologically or cytologically confirmed stage IIIB (malignant pericardial or pleural effusion) or stage IV non-small cell lung cancer;

4. Has non-squamous, non-small cell lung cancer

5. Has measurable disease, defined as at least one tumor that fulfills the criteria for a target lesion according to RECIST;

6. Has an ECOG performance status of 0 or 1;

7. Has a life expectancy of > 3 months;

8. Has adequate hematologic function as evidenced by:

   1. ANC ≥ 1,500/μL
   2. PLT ≥ 100,000/μL
   3. HGB ≥ 9 g/dL obtained within 1 week prior to the first dose of study medication;

9. Has adequate renal function as evidenced by:

   1. Serum creatinine ≤ 1.5 X the upper limit of normal (ULN) for the reference lab
   2. 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;

10. Has adequate hepatic function as evidenced by:

    1. Serum total bilirubin ≤ 1.0 mg/dL
    2. AST ≤ 2.5X ULN for the reference lab (≤ 5X ULN for subjects with known hepatic metastases)
    3. 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;

11. Has adequate coagulation function as evidenced by:

    1. INR ≤ 1.5
    2. PTT ≤ ULN for the reference lab obtained within 1 week prior to the first dose of study medication;

12. 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:

1. Has received prior systemic chemotherapy at any time for lung cancer;

2. Has received previous radiation therapy to >30% of active bone marrow or any radiation therapy within 3 weeks of Day 1;

3. Has a known hypersensitivity to baker's yeast, or has an active yeast infection;

4. Has had previous exposure to Betafectin® or Imprime PGG;

5. Has an active infection;

6. Presents with any of the following medical diagnoses/conditions at the time of screening:

   1. Central nervous system (CNS) metastases
   2. Uncontrolled hypertension (>150/100 mmHg) or hypertension that requires > two agents for adequate control
   3. Peripheral neuropathy ≥ grade 2 from any cause
   4. Fever of >38.5° C within 3 days prior to screening or Day 1, initial dosing
   5. 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

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

   1. Arterial or venous thromboembolic or hemorrhagic disorders including stroke, transient ischemic attack or cerebral infarction
   2. Deep vein thrombosis within 1 year prior to screening
   3. 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
   4. 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

8. Has a known hypersensitivity to bevacizumab, murine proteins, or any component of bevacizumab;

9. Has a know sensitivity to polyethoxylated castor oil;

10. Has previously received treatment with bevacizumab;

11. Has had surgery within 4 weeks of Day 1 or needle or open biopsy within 1 week of Day 1;

12. Has a non-healing wound or gastric ulcer;

13. Has a non-healed bone fracture;

14. Is receiving systemic anti-coagulation therapy (e.g., dipyridalmole (Persantine®), ticlopidine (Ticlid®), clopidogrel (Plavix®) and /or cilostazol (Pletal®);

15. 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;

16. Presents with any of the following medical diagnoses/conditions at the time of screening:

    a. Predominant squamous cell histology

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

    1. Hemoptysis (≥ ½ tsp red blood)
    2. Bleeding diathesis or coagulopathy

18. If female, is pregnant or breast-feeding;

19. 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);

20. Has previously received an organ or progenitor/stem cell transplant.