Up to an additional 44 subjects will be enrolled in an expansion phase of this study (for a total of up to 60 subjects) to obtain additional safety, immune and efficacy data. Subjects will be enrolled into 2 mutually exclusive cohorts described below. Cohort 1: At least 32 subjects will receive 2 prime vaccinations (PV) of CRS -207 (1 × 109 CFU given i.v. over approximately 1 hour) 2 weeks apart followed 2 weeks later by up to 6 cycles of pemetrexed and cisplatin 3 weeks apart. Three weeks after completion of chemotherapy, subjects will receive an additional 2 infusions (boost vaccinations; BV) of CRS -207 3 weeks apart (Figure 1 ). Subjects enrolled in Cohort 1 include the 16 subjects originally planned plus a minimum of the first 16 subjects enrolled into the expansion phase. Cohort 2: The remaining subjects enrolled in the expansion phase (up to 28 total) will receive CRS -207 in combination with chemotherapy at the dose and schedule described above, however, these subjects will also receive low -dose Cy (200 mg/m 2) over 30 minutes one day prior to each CRS-207 infusion (i.e. prior to each PV and BV infusion). All subjects will return to the clinic 4 weeks after their 2nd boost vaccination for an End of Course (EOC ) visit. Subjects will have follow -up visits 4 weeks after the EOC visit and every 8 weeks thereafter until treatment discontinuation . Subjects will continue to receive maintenance vaccinations (MV) with (Cohort 2) or without Cy (Cohort 1) following their original schedule at each follow- up visit if they are clinically stable and continue to meet dosing eligibility . Subjects may continue on treatment with radiographic disease progression if subject is clinically stable and investigator believes the treatment may be providing benefit. The study will consist of a screening p eriod (within 28 days of the first administration of study drug), followed by administration of test treatments per Figure 2. Tumor assessment by computed tomography (CT) with optional fluorodeoxyglucose positron emission tomography (FDG -PET) or magnetic Aduro Biotech , Inc. Protocol ADU -CL-02-v8 CRS -207 with Pemetrexed and Cisplatin Version 8, 08 March 2018 Page 11 resonance imaging (MRI) will be performed every 6 -8 weeks until subject comes off study. Tumor biopsies, which are optional, will be performed pre -treatment, before start of chemotherapy (i.e. after initial 2 infusions of CRS -207) , after completion of chemotherapy, and after CRS -207 to evaluate tumor lymphocytic (e.g. CD4, CD8 , T reg) infiltrate. A seven -day course of antibiotics will be administered to eliminate any residual CRS -207 beginning 7 days following the second infusion of CRS -207 during the induction phase, and after the final study dose of CRS-207. Figure 2. Study Treatment Timeline, Doses Scheduled and Follow -up *Or investigator believes subject is no longer receiving benefit if treatment continued beyond radio graphic progression To monitor initial safety of the sequential vaccine regimen, no more than 1 subject per week will be enrolled for the first 6 subjects. Dose -limiting toxicities are defined in Section 3.6. If >33% of subjects (i.e. 1 out of 3 subjects) experience a dose- limiting toxicity during the study , the dose will be lowered to 3 × 108 CFU for all subsequent dosing with CRS -207. Blood will be collected at EOS to assess the clearance of CRS -207. Safety will be assessed by collection of data on AEs, vital signs, physical examination, clinical hematology, serum chemistry , and deaths . Induction of CRS-207 q 2 weeks x2 infusions4 3 14 Weeks5 8 11 17 20 23 26 Pemetrexed plus Cisplatin q 3 weeks x up to 6 cyclesCRS-207 q 3 w eeks x 2 infusionsq8wks -Screening30Immune Analysis Follow -up (beginning Week 34) Until Disease Progression*1 Prime Vaccination (PV)Chemotherapy Treatment (CY)Boost Vaccination (BV)Maintenance Vaccinations (MV) CRS-207 (with or without CY given one day prior) q 8 weeks (eligible subjects)(with or without CY given one day prior)(with or without CY given one day prior )I I .J, .J, .J, .J, .J, .J, .J, I I I I I I I I I I I I I lJ tt u u u u u u t t > I I I I Aduro Biotech , Inc. Protocol ADU -CL-02-v8 CRS -207 with Pemetrexed and Cisplatin Version 8, 08 March 2018 Page 12 immune response to mesothelin will be evaluated by ELISPOT assay prior to treatment and at time points during and after treatment. Objective tumor response , progression free survival and time to progression will be measured using modified RECIST for assessment of response in MPM (Appendix A ) and immune -related response criteria. 47 Other evaluations will include overall survival, immune subset analysis (e.g. CD4, CD8, Treg) and gene expression profiling of tumor tissue pr e and post vaccination by immunohistochemistry, evaluating induction of anti -mesothelin humoral immune response by ELISA, assessing tumor marker kinetics by measuring serum levels of mesothelin and CA-125 and plasma osteopontin. 3.2 STUDY POPULATION 3.2.1 Inclusion Criteria To be considered eligible to participate in this study, subjects must meet the inclusion criteria listed below: (1) Subjects must have histologically -confirmed epithelial or biphasic pleural mesothelioma not amenable to potentially curative surgical resection at the time of study entry (subjects with biphasic tumors that have a predominantly ( ≥50%) sarcomatoid component will be excluded) (2) Measurable disease, as defined by modified RECIST for MPM 4 (3) ECOG Performance Status of 0 or 1 (4) Normal organ and marrow function, as defined by: • Absolute neutrophil count (ANC) ≥ 1,500/ µl • Platelet count ≥ 100,000/ µl • Bilirubin ≤ 1.5 × upper limit of normal (ULN), or bilirubin ≤ 3× ULN if due to Gilbert’s disease • AST and ALT ≤ 2.5× ULN • Albumin ≥ 2.5 g/dL • Creatinine clearance ≥ 50 mL/min per Cockcroft -Gault formula (Creatinine clearance = {[(140- age) x weight in kilograms] x [0.85 if female] }/[72 x creatinine in mg/dL]) • CD4 ≥ 0.2× 109/L • Hemoglobin ≥ 9.0 g/dL Aduro Biotech , Inc. Protocol ADU -CL-02-v8 CRS -207 with Pemetrexed and Cisplatin Version 8, 08 March 2018 Page 13 (5) Age 18 years and over (6) Must have pulmonary function testing with documented values for vital capacity ( VC) and forced expiratory volume in 1 second (FEV 1) > 45% of predicted value and oxygen saturation ≥ 90% on room air, as measured by pulse oximeter (7) Antic ipated life expectancy greater than 6 months (8) Female subjects of childbearing potential must consent to use a medically acceptable method of highly effective contraception (oral hormonal contraceptive, condom plus spermicide, or hormone implants) throughout the study period and for 28 days after their final study drug administration (A barrier method of contraception must be employed by all subjects (male and female), regardless of other methods.) (9) Subject provides informed consent and is willing and able to comply with all study procedures 3.2.2 Exclusion Criteria To be eligible for entry into the study, subjects must not meet any of the exclusion criteria listed below: (1) Be a candidate for curative surgery at the time of study entry (2) Have had s urgery or pleurodesis within 2 weeks prior to dosing (3) Have had prior radiotherapy (except palliative extra- thoracic localized radiotherapy) or biologic therapy for MPM within 3 weeks prior to dosing (4) Have had prior systemic chemotherapy for MPM (Prior intracavitary cytotoxic drugs or immunomodulators are not permitted, unless given for the purpose of pleurodesis.) (5) Have an active malignancy with the exception of any of the following: • adequately treated basal cell carcinoma • squamous cell carcinoma of the skin, or in si tu cervical cancer Aduro Biotech , Inc. Protocol ADU -CL-02-v8 CRS -207 with Pemetrexed and Cisplatin Version 8, 08 March 2018 Page 14 • adequately treated Stage I cancer from which the subject is currently in remission and has been in remission for ≥ 3 years • Stage I prostate cancer that does not require treatment • any other cancer from which the subje ct has been disease- free for ≥ 2 years (6) Have documented and ongoing central nervous system (CNS) involvement with their malignant disease (history of CNS involvement is not an exclusion criterion but the CNS metastases should have been adequately treated [radiation or surgical resection] and subjects are neurologically stable for 3 months off steroids) (7) Have any evidence of clinical ly significant ascites (8) Have clinically significant pleural effusion (9) Have clinically significant heart disease (such as uncontrolled angin a, myocardial infarction within 3 months, congestive heart failure of New York Heart Association III or IV) (10) Have valvular heart disease that requires antibiotic prophylaxis for prevention of endocarditis, consistent with American Heart Association (AHA) guidelines (11) History of any autoimmune disease, including patients with a history of inflammatory bowel disease, (including ulcerative colitis and Crohn ’s Disease), patients with a history of symptomatic disease (e.g. rheumatoid arthritis, systemic progressive sclerosis [scleroderma], systemic lupus erythematosus, autoimmune vasculitis [e.g.