Safety and Efficacy of Listeria in Combination With Chemotherapy as Front-line Treatment for Malignant Pleural Mesothelioma

Inclusion Criteria: * Have histologically confirmed epithelial or biphasic MPM not amenable to potentially curative surgical resection (subjects with biphasic tumors that have a predominantly (≥50%) sarcomatoid component will be excluded) * Be at least 18 years of age * Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 * Have an anticipated life expectancy of greater than 6 months * For women and men of childbearing potential, a medically acceptable method of highly effective contraception (oral hormonal contraceptive, condom plus spermicide, or hormone implants) must be used throughout the study period and for 28 days after their final vaccine administration. (A barrier method of contraception must be employed by all subjects \[male and female\], regardless of other methods.) * Be willing and able to give written informed consent, and be able to comply with all study procedures * Have adequate organ function as defined by specified laboratory values Exclusion Criteria: * A candidate for curative surgery * Surgery within 2 weeks prior to dosing * Prior radiotherapy or biologic therapy * Treatment with an investigational agent within 4 weeks before dosing * Prior systemic chemotherapy * Currently have or have history of certain study-specified heart, liver, kidney, lung, neurological, immune or other medical conditions * Documented and ongoing brain metastases * Have any evidence of hepatic cirrhosis or clinical or radiographic ascites * Have clinically significant and/or malignant pleural effusion * Known or suspected allergy or hypersensitivity to yeast or any other component of CRS-207 (e.g., glycerol), Platinol or platinum-containing compounds, or pemetrexed * Used any systemic steroids within 28 days of study treatment * Use more than 3 g/d of acetaminophen * An artificial (prosthetic) joint or other artificial implant or device that cannot be easily removed (with some exceptions for dental and breast implants and biliary stents and mediports) * Infection with HIV or hepatitis B or C at screening * Any immunodeficiency disease or immunocompromised state or active autoimmune disease or history of autoimmune disease requiring systemic steroids or other immunosuppressive treatment * Be a woman who is pregnant or breastfeeding * Unable to avoid close contact with another individual known to be at high risk of listeriosis (e.g., newborn infant, pregnant woman, HIV-positive individual) during the course of CRS-207 treatment until completion of antibiotic regimen * Conditions, including alcohol or drug dependence, intercurrent illness, or lack of sufficient peripheral venous access, that would affect the patient's ability to comply with study visits and procedures