• Establish the maximum tolerated dose and dose-limiting toxicities of the combination of OSI-774 (Tarceva™) and rhuMAb VEGF (Avastin™). [ Time Frame: 33 Months ] [ Designated as safety issue: No ]
  
• Assess response rate and tolerability of the regimen at the dose level established in the phase I portion of this study. [ Time Frame: 33 Months ] [ Designated as safety issue: No ]
  

• Evaluate the pharmacokinetic interaction between the combination. [ Time Frame: 33 Months ] [ Designated as safety issue: No ]
  
• Establish a phase II regimen of the OSI-774/ rhuMAb VEGF combination, for further study alone or in combination with cytotoxic chemotherapy. [ Time Frame: 33 Months ] [ Designated as safety issue: No ]
  

Inclusion:

• Patient has histologically proven stage IIIB with pleural effusion, stage IV or recurrent non-squamous NSCLC.
• Patient has a Karnofsky performance status >=70%.
• Patient has adequate bone marrow function: WBC >= 3,000 cells/mm3, ANC >= 1,500 cells/mm3, platelet count >= 100,000 cells/mm3, Hgb >= 9.0 g/dL.
• Patient has adequate liver function: total bilirubin level <= 2.0 mg/dL, albumin >= 2.5 g/dL.
• Transaminases (SGOT and/or SGPT) and alkaline phosphatase may be up to 2.5 x ULN.
• Patient has adequate renal function: a serum creatinine < 2 mg/dl
• Patient has signed a written informed consent.
• Patient has received at least one prior chemotherapeutic regimen for recurrent or metastatic disease.

Exclusion:

• Patient has not received prior chemotherapeutic regimens for advanced disease.
• Patient has received prior biologic therapy targeting EGFR and/or VEGF.
• Patient has received radiation therapy within the past 3 weeks.
• Patient has signs or symptoms of acute infection requiring systemic therapy.
• Patient exhibits confusion, disorientation, or has a history of major psychiatric illness that may impair patient's understanding of the informed consent.
• Patient requires total parenteral nutrition with lipids.
• Patient has a history of uncontrolled heart disease and/or uncontrolled hypertension (> 150/100 mmHg).
• Because of the possible teratogenic effect, pregnant women and women who are currently breast-feeding may not participate in this study. - All women of childbearing potential must have a negative pregnancy test within 24 hours prior to enrolling in the study.
• Serious infection or other intercurrent illness requiring immediate therapy.
• Clinical/imaging evidence of CNS malignancy or with recently treated CNS malignancy, as well as those experiencing recent CVA or other CNS bleeding.
• Pediatric patients in whom open growth plates would be expected.
• Urine protein qualitative value of > 30 in urinalysis or > +1 in proteinuria testing by dipstick.
• Patient has a clinical history of coagulopathy or thrombosis.
• Patient is currently receiving or intending to receive anti-coagulants.
• Patient has had a recent myocardial infarction (still inside the healing period). Note: a six-month window is optimal.
• Patient is recovering from recent major surgery (e.g., less than 2 weeks since surgery) or is anticipating major surgery.
• Patient has a clinical history of hemoptysis or hematemesis.
• Patient may not have PEG or G tube.