Phase 2 Study of REOLYSIN® in Combination With Paclitaxel and Carboplatin for Non-Small Cell Lung Cancer With KRAS or EGFR Activation

Inclusion Criteria: * have histologically or cytologically confirmed stage IIIB (pleural effusion; IVA on revised IASLC staging) or stage IV, or recurrent, non-small cell lung cancer with evidence of RAS- or EGFR- activation in their tumors, as defined by EGFR activating mutations in exons 18 to 21, EGFR FISH amplification, or K-ras mutations in exon 2 (codons 12,13,61). * have evidence of measurable disease. For patients previously irradiated, the measurable lesion(s) must be outside of the treated field. * be chemotherapy naïve for their metastatic or recurrent NSCLC. Prior adjuvant chemotherapy or chemo-XRT for treatment of localized disease is allowed, provided it has been ≥ 6 months since the last chemotherapy infusion. Previous radiation for palliative purposes is also allowed, as long as it has been ≥4 weeks from the last dose. * Patients who have been previously treated with EGFR tyrosine kinase inhibitors as their only systemic treatment are eligible, provided this treatment has been discontinued for ≥4 weeks. Patients who have received erlotinib as first line treatment without chemotherapy and experience tumor progression will be eligible. * have NO continuing acute toxic effects (except alopecia) of any prior radiotherapy, chemotherapy, or surgical procedures, i.e., all such effects must have resolved to Common Terminology Criteria for Adverse Events (CTCAE, version 3.0) Grade ≤ 1. Surgery (except biopsies) must have occurred at least 28 days prior to study enrollment. * have an ECOG Performance Score of ≤ 2. * have a life expectancy of at least 3 months. * have baseline laboratory results as follows: * Absolute neutrophil count (ANC) ≥ 1.5 x 10E9 \[SI units 10\^9/L\] * Platelets ≥ 100 x10E9 \[SI units 10E9/L\] (without platelet transfusion) * Hemoglobin ≥ 9.0 g/dL \[SI units gm/L\] (with or without RBC transfusion) * Serum creatinine ≤ 1.5 x upper limit of normal (ULN) * Bilirubin ≤ 1.5 x ULN * AST/ALT ≤ 2.5 x ULN * Negative pregnancy test for females of childbearing potential. * be willing and able to comply with scheduled visits, the treatment plan, and laboratory tests. Exclusion Criteria: * Receive concurrent therapy with any other anticancer agent while on study. * Received chemotherapy within 6 months, or radiotherapy or EGFR therapy within 4 weeks, prior to entering the study or have not recovered from adverse events due to agents administered more than 4 weeks earlier. * Have brain metastases. Patients with resected oligometastasis are eligible if post resection MRI demonstrates resolution. Gamma knife treated patients are also eligible, if there are no more than two treated metastases confined to the same area of the brain and a post treatment MRI shows a decrease in the metastases. * Have ≥ grade 2 peripheral neuropathy at baseline. * Have uncontrolled cardiac dysfunction, including a myocardial infarction in the preceding 6 months, or known cardiac ejection fraction \< 40%. * Be on immunosuppressive therapy or have known HIV infection or active hepatitis B or C. * Be a pregnant or breast-feeding woman. Female patients of childbearing potential must agree to use effective contraception, must be surgically sterile, or must be postmenopausal. Male patients must agree to use effective contraception or be surgically sterile. Barrier methods are a recommended form of contraception. * Have uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/ social situations that would limit compliance with study requirements. * Have dementia or altered mental status that would prohibit informed consent. * Have any other severe, acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration or may interfere with the interpretation of study results and, in the judgment of the Principal Investigator, would make the patient inappropriate for this study.