Table 1. Dosing-Eligibility Requirements Hematologic Renal Hepatic ANC ≥1,500/µL Platelets ≥100,000/µl Hemoglobin ≥9 g/dL CD4 ≥ 0.2×10 9/L prior to 1st post- chemotherap y CRS-207 boost vaccination Creatinine ≤2.0 × ULN AST/ALT ≤2.5× ULN Bilirubin ≤1.5× ULN or bilirubin ≤ 3× ULN if due to Gilbert’s disease ALT = alanine aminotransferase; ANC = absolute neutrophil count ; AST = aspartate aminotransfera se; ULN = upper limit of normal ; WBC = white blood cell. * Cockcrof t-Gault formula: Creatinine Clearance = {[(140-age) x weight in kilograms] x [0.85 if female]}/[72 x creatinine in mg/dL] Aduro Biotech , Inc. Protocol ADU -CL-02-v8 CRS -207 with Pemetrexed and Cisplatin STUDY SYNOPSIS (continued) Vers ion 8, 08 March 2018 Page ix 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 Prohibited medications: The following therapies are not permitted during the study and may result in early termination of the subject from treatment: •Non-study chemotherapy or immunotherapy (approved or investigational) •Systemically active steroids for more than 3 days or use of any systemic steroids within 14 days before or after dosing , with exception of study- prescribed steroids. •TNF pathway inhibitors or PI3 kinase inhibitors •Any other investigational product In addition, the following therapies should not be administered unless medically necessary, and approval must be obtained from the medical monitor for a subject to continue dosing if therapy is given concurrently with study participation: •General anesthesia or deep sedation •Aspirin >325 mg/d (chronic daily use of aspirin ≤325 mg/d and heparin flushes for central lines are allowed) •More than 4 g/d of acetaminophen •Systemic antibiotics If subjects receive immunosuppressive medications on or after study, prophylactic antibiotics to prevent CRS -207 infection a re strongly recommended for the duration of the treatment with the immunosuppressant (recommended oral 80 mg trimethoprim / 400 mg sulfamethoxazole once daily or 160 mg trimethoprim / 800 mg sulfamethoxazole (DS) three days a week). Filgrastim (Neupogen o r G-CSF) or Sargramostin (Leukine or GM -CSF) should not be administered 14 days prior to or 14 days after any CRS -207 dose. Approval must be obtained from the medical monitor for a subject to continue dosing if administered within this timeframe. Prophyl actic vaccines (e.g. pneumococcal vaccine, influenza vaccine) should not be administered 28 days prior to or 28 days after any CRS -207 dose. Approval must be obtained from the medical monitor for a subject to continue dosing if a prophylactic vaccine is a dministered within this timeframe. Aduro Biotech , Inc. Protocol ADU -CL-02-v8 CRS -207 with Pemetrexed and Cisplatin STUDY SYNOPSIS (continued) Version 8, 08 March 2018 Page x 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 Test product, dose, and mode of administration: CRS -207 [Cohort 1 and Cohort 2] : CRS-207, live -attenuated Lm encoding human mesothelin, will be given i.v. over approximately 1 hour at 1 × 109 colony -forming units (CFU ); reconstituted in approximately 100 mL 0.9% sodium chloride for 2 infusions (prime vaccinations) 2 weeks apart prior to receiving pemetrexed and cisplatin chemotherapy, and for 2 infusions (boost vaccinations) 3 weeks apart following chemotherapy . Subje cts who continue to meet dosing eligibility will receive maintenance vaccinations of CRS -207 beginning at the first follow -up visit and every 8 weeks thereafter during follow -up phase . Pemetrexed [Cohort 1 and Cohort 2] : ALIMTA®, pemetrexed disodium heptahydrate (pemetrexed), has a recommended dose of 500 mg/m2 body surface area ( BSA ) in 100mL 0.9% sodium chloride administered over 10 minutes as an intravenous infusion on Day 1 of a 21- day cycle. Up to 6 cycles of pemetrexed and cisplatin will be given after the initial 2 infusions of CRS- 207. Cisplatin [Cohort 1 and Cohort 2] : Cisplatin, USP (cis -diamminedichloroplatinum) , has a recommended dose of 75 mg/m2 BSA in 1L 0.9% sodium chloride with ma nnitol 30g/L infused over 2 hours, beginning approximately 30 minutes after the end of pemetrexed administration on Day 1 of each 21 -day cycle. Up to 6 cycles of pemetrexed and cisplatin will be given after the initial 2 infusions of CRS -207. Cyclophospha mide [Cohort 2]: 200 mg/m2 in 100 mL normal saline administered by i.v. infusion over 30 minutes one day prior to CRS -207. Study duration: The duration of one full treatment course [i.e. C RS-207 with or without Cy (2 infusions, 2 weeks apart), pemetrexed (500 mg/m2) and cisplatin (75 mg/m2) every 3 weeks × 6 cycles, CRS -207 with or without Cy (2 infusions , 3 weeks apart )] is 25 weeks . Subject s enrolled in Cohort 1 will receive CRS -207 and pemetrexed and cisplatin per the schedule described abo ve. Subjects enrolled in Cohort 2 will receive Cy/CRS -207 and pemetrexed and cisplatin per the schedule described above. Clinical and immune response assessments will be performed 4 weeks after EOC . Eligible subjects will receive maintenance vaccinations of CRS -207 (with or without Cy) beginning at the first follow - up visit and every visit thereafter . Reference therapy, dose, and mode of administration: There is no reference therapy or placebo administered in this study. Criteria for Evaluation: Safety: Safety will be assessed by collection of data on AEs, vital signs, physical examination, clinical hematology, serum chemistry , deaths , and blood cultures for CRS -207 clearance. Efficacy: Induction of immune response to mesothelin will be evaluated by IFN-gamma ELISPOT assay prior to treatment and at time points during and after treatment. Other evaluations will include immune subset analysis ( e.g. CD4, CD8 , T reg) by immunohistochemistry and gene expression profiling of tumor tiss ue pre and post vaccination , 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. Objective tumor response, progression free su rvival and time to progression will be measured using modified RECIST for assessment of response in MPM (Appendix A) and immune -related response criteria (irRC; Appendix B) . Pulmonary function will be measured by forced vital capacity ( FVC ), forced expira tory volume in 1 second (FEV1 ) and vital capacity ( VC). Data analysis: The sample size of the study was originally planned to enroll up to 16 subjects in order to evaluate the induction of Aduro Biotech , Inc. Protocol ADU -CL-02-v8 CRS -207 with Pemetrexed and Cisplatin STUDY SYNOPSIS (continued) Version 8, 08 March 2018 Page xi 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 immune response to mesothelin and initial safety of CRS -207 combined with pemetrexed and cisplatin chemotherapy. Up to 44 additional subjects will be enrolled in an expansion phase to obtain additional safety , immune and preliminary efficacy data.