Up to an additional 44 subjects will be enrolled in an expans ion 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 infusions (prime vaccinations; PV) of CRS -207 (1 × 10 9 CFU given intravenously [ 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. 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 r emaining 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, h owever, these subjects will also receive low-dose Cy (200 mg/m 2) intravenously over 30 minutes one day prior to each CRS -207 infusion ( i.e. prior to each PV and BV infusion). Low-dose Cy inhibits regulatory T cells and enhances immune responses when given in context with vaccine s1-3. Preclinical studies of low -dose Cy given prior to CRS -207 in mouse tumor models have shown improve d immunogenicity and survival ( Section 1.3). All subjects will return to the clinic 4 weeks after their 2 nd 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 I Aduro Biotech , Inc. Protocol ADU -CL-02-v8 CRS -207 with Pemetrexed and Cisplatin STUDY SYNOPSIS (continued) Version 8, 08 March 2018 Page iv Name of Sponsor Company: Aduro Biotech , Inc. Individual Study Table Referring to Part of the Dossier Volume: Page: (For National Authority Use Only) Name of Finished Product: CRS -207; pemetrexed ; cisplatin; cyclophosphamide Name of Active Ingredients: Pemetrexed : C20H19N5Na2O6·7H 2O Cisplatin: PtCl 2H6N2 CRS -207: Lm ΔactA/ΔinlB/hMes o Cyclophosphamide (Cy): C7H15Cl2N2O2P•H 2O discontinuation . Subjects who continue to meet dosing eligibility will receive additional CRS -207 infusions (maintenance vaccinations; MV) , with or without Cy following their original schedule, at every follow -up visit . Subjects may continue on treatment with radiographic disease progression if subject is clinically stable and investigator be lieves the treatment may be providing benefit. See figure below for dosing schedule (based on full regimen of 6 chemotherapy cycles). *Or investigator believes subject is no longer receiving benefit if treatment continued beyond radiographic progressi on Safety and follow -up: The i nitial safety of CRS -207 (with or without Cy), pemetrexed and cisplatin treatment will be monitored closely. Subjects will be followed for AEs and dose -limiting toxicities ( Section 3.6 ) which may warrant either CRS -207 dose reduction or halting treatment after review by the lead investigator, sponsor and medical monitor. A 7-day course of oral amoxicillin or trimethoprim/sulfamethoxazole (in penicillin -allergic subjects ) will be administered to eliminate any residual CRS -207 beginning 7 days following the second dose (prime vaccination) of CRS -207 during the induction phase and after the final study dose of CRS -207. All subjects will complete an End of Study (EOS ) visit no more than four weeks following the final dose of study medication or prior to receipt of other cancer -related 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 "'"' "' "' "' "' "' I I I I I I I I I I I I I u tt tl tl tl tl tl tl t t > I I I I Aduro Biotech , Inc. Protocol ADU -CL-02-v8 CRS -207 with Pemetrexed and Cisplatin STUDY SYNOPSIS (continued) Version 8, 08 March 2018 Page v Name of Sponsor Company: Aduro Biotech , Inc. Individual Study Table Referring to Part of the Dossier Volume: Page: (For National Authority Use Only) Name of Finished Product: CRS -207; pemetrexed ; cisplatin; cyclophosphamide Name of Active Ingredients: Pemetrexed : C20H19N5Na2O6·7H 2O Cisplatin: PtCl 2H6N2 CRS -207: Lm ΔactA/ΔinlB/hMes o Cyclophosphamide (Cy): C7H15Cl2N2O2P•H 2O treatment . To eliminate any potentially residual CRS -207, subjects will be administered a 7 -day course of antibiotics beginning at the EOS visit and prior to receiving any subsequent cancer -related therapy. Blood will be collected at EOS to assess the clearance of CRS -207 . Subjects will return to the study site for an End of Course (EOC) visit approximately 4 weeks after their 2nd boost vaccination for safety , clinical response, and immune resp onse evaluations. Thereafter, 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. Number of subjects (planned): Up to 16 subjects with MPM who meet all eligibility criteria were originally planned to be enrolled in the study. Up to 44 additional subjects (for a total of 60 subjects) with MPM who meet all eligibility criteria will be enrolled in an expansion phase of the study . Subject discontinuation: A subject may be removed from the s tudy for the following reasons: (1) Occurrence of an adverse event that presents an unacceptable consequence or risk to the subject (2) Development of an illness or complication (including progressive disease) that justifies withdrawal from the study, as determined by the investigator and medical monitor (3) Noncompliance: failure to receive clinical study medication or treatment as mandated by the protocol, or failure to comply with protocol requirements (4) Study discontinued by the sponsor Subjects who withdraw consent or are removed from the study before completing at least 4 cycles of chemotherapy may be replaced at the discretion of the investigator and Aduro Biotech, Inc . (Aduro). Subjects may continue on treatment with radiographic disease progression if subject is clinically stable and the investigator believes the treatment is providing benefit. Aduro Biotech, Inc. Protocol ADU-CL-02-v8 CRS-207 with Pemetrexed and Cisplatin STUDY SYNOPSIS (continued) Version 8, 08 March 2018 Page vi Name of Sponsor Company: Aduro Biotech, Inc. Individual Study Table Referring to Part of the Dossier Volume: Page: (For National Authority Use Only) Name of Finished Product: CRS-207; pemetrexed; cisplatin; cyclophosphamide Name of Active Ingredients: Pemetrexed: C 20H19N5Na2O6ꞏ7H 2O Cisplatin: PtCl 2H6N2 CRS-207: Lm ΔactA/ΔinlB /hMeso Cyclophosphamide (Cy): C7H15Cl2N2O2P•H 2O Inclusion criteria: Subjects must meet all of the following criteria to be eligible to participate in the study: (1) Subjects must have histologically-confirmed epithelial or bipha sic pleural mesothelioma not amenable to potentially curative surgical resection at the time of study en try (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) Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 (4) Normal organ and marrow function, as defined by:  ANC ≥ 1,500/µl  Platelet count ≥ 100,000/µl  Bilirubin ≤ 1.5 × upper limit of n ormal (ULN), or bilirubin ≤ 3 × ULN if due to G ilbert’s disease  AST and ALT ≤ 2.5× ULN  Albumin ≥ 2.5 g/dL  Creatinine clearance ≥ 50 mL/min per Cockcroft-Gault formula (C reatinine 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 (5) Age 18 years and over (6) Must have pulmonary function testing with documented values for VC and FEV 1 > 45% of predicted value and oxygen saturation ≥ 90% on room air, as measured by pulse oxime ter (7) Anticipated 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 spermic ide, or hormone implants) throughout the study period and for 28 days after their final study drug administrat ion (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 willin g and able to compl y with all stud y procedures Exclusion criteria: Subjects must not meet any of th e following criteria to be eligible to participate in the study: (1) Be a candidate for curative surgery at the time of study entry (2) Have had surgery or pleurodesis within 2 weeks prior to dosing (3) Have had prior radiotherapy (e xcept palliative extra-thoracic l ocalized radiotherapy) o r biologic therapy for MPM within 3 weeks prior to dosing (4) Have had prior systemic chemot herapy for MPM. P rior intracavita ry 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 foll owing:  adequately treated basal cell carcinoma  squamous cell carcinoma of the skin, or in situ cervical cancer  adequately treated Stage I cancer from which the subject is cur rently 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 subject has been disease-free f or ≥ 2 years (6) Have documented and ongoing central nervous system (CNS) involv ement with their malignant disease [history of CNS involvement is not an exc lusion criterion but the CNS me tastases should have been adequatel y treated Aduro Biotech, Inc. Protocol ADU-CL-02-v8 CRS-207 with Pemetrexed and Cisplatin STUDY SYNOPSIS (continued) Version 8, 08 March 2018 Page vii Name of Sponsor Company: Aduro Biotech, Inc. Individual Study Table Referring to Part of the Dossier Volume: Page: (For National Authority Use Only) Name of Finished Product: CRS-207; pemetrexed; cisplatin; cyclophosphamide Name of Active Ingredients: Pemetrexed: C 20H19N5Na2O6ꞏ7H 2O Cisplatin: PtCl 2H6N2 CRS-207: Lm ΔactA/ΔinlB /hMeso Cyclophosphamide (Cy): C7H15Cl2N2O2P•H 2O (radiation or surgical resection) and subjects are neurological ly stable for 3 months off steroids] (7) Have any evidence of clinically significant ascites (8) Have clinically significant pleural effusion (9) Have clinically significant heart disease (such as uncontrolled angina, myocardial infarction within 3 months, congestive heart failure of New York Heart Association III or I V) (10) Have valvular heart disease that requires antibiotic prophylaxi s for prevention of endoc arditis, consistent with American Heart Associa tion (AHA) guidelines (11) History of any autoimmune disease, including patients with a hi story of inflammatory bowel disease, (including ulcerative colitis and Crohn’s Dis ease), patients with a history of symptomatic disease (e.g. rheumatoid arthritis, systemic progressive sclerosis [ scleroderma], systemic lupus er ythematosus, autoimmune vasculitis [e.g.