15 5.2.7. Missing, Unused and Incomplete Data ............................ 15 5.3. Timing of Analyses .................................................................... 16 5.4. Subject Disposition ................................................................... 16 5.5. Demographic and Baseline Characteristics ....................... 16 5.6. Prior Anti -Cancer Therapies .................................................... 17 5.7. Medical History ........................................................................... 17 5.8. Concomitant Medications ........................................................ 17 5.9. Other Assessments ................................................................... 17 5.10. Treatment Exposure .................................................................. 17 5.11. Efficacy Evaluation .................................................................... 18 5.11.1. Tumor Evaluations and Overall Tumor Response ........... 18 5.11.2. Exploratory Endpoints ..................................................... 18 5.12. Safety Analyses .......................................................................... 18 5.12.1. Adverse Events ................................................................ 18 5.12.2. Deaths .............................................................................. 19 5.12.3. CRS -207 Infusion- related Reactions ............................... 19 5.12.4. Dose Limiting Toxicities ................................................. 20 5.12.5. Laboratory Data ............................................................... 20 5.12.6. Vital Signs and Physical Examinations ........................... 20 5.12.7. Electrocardiogram ............................................................ 21 5.12.8. ECOG Performance Status .............................................. 21 6. CHANGES TO PLANNED ANALYSES ............................................... 22 7. REFERENCES ......................................................................................... 23 8. LIST OF TABLES, FIGURES AND LISTINGS FOR FINAL ANALYSIS ................................................................................................ 24 Aduro Biotech, Inc. CONFIDENTIAL Protocol ADU -CL-02 Final Version 1 Page 5 of 24 04MAY2018 ABBREVIATIONS Abbreviation Definition AE Adverse Events ALT Alanine aminotransferase ANC Absolute neutrophil count AST Aspartate aminotransferase ATC Anatomic Therapeutic Chemical BMI Body Mass Index BSA Body Surface Area BV Boost Vaccination CFU Colony -forming units CI Confidence Interval CSR Clinical Study Report CR Complete Response CRF Case Report Form Cy Cyclophosphamide DCR Disease control rate DLT Dose L imiting Toxicity DMC Data Monitoring Committee DPFU Diseas e Progression Follow -Up Period ECG Electrocardiogram ECOG Eastern Cooperative Oncology Group ELISPOT Enzyme -Linked Immunosorbent Spot EOC End of Course EOS End of Study FAS Full Analysis Set FDA Food and Drug Administration FEV1 Forced Expiratory Volume in 1 Second FVC Forced Vital Capacity HLA Human leukocyte antigen ICH International Council on Harmonisation IFN-γ Interferon gamma irRC Immune -Related Response Criteria iDAP Immune Data Analysis Plan MedDRA Medical Dictionary for Regulatory Activities MPM Malignant Pleural Mesothelioma mRECIST Modified Response Evaluation Criteria in Solid Tumors MV Maintenance Vaccinations NCI CTCAE National Cancer Institute Common Toxicity Criteria for Adverse Ev ents OS Overall Survival PBMC Peripheral blood mononuclear cell (s) PD Progressive Disease PFS Progression -free Survival PFTs Pulmonary Function Tests PR Partial Response PT Preferred Term Aduro Biotech, Inc. CONFIDENTIAL Protocol ADU -CL-02 Final Version 1 Page 6 of 24 04MAY2018 Abbreviation Definition PV Prime Vaccination RBC Red blood cell RECIST Response Evaluation Criteria in Solid Tumors SAE Serious Adverse Event SAP Statistical Analysis Plan SD Stable Disease , Standard Deviation SI International System of Units SOC System Organ Class TEAE Treatment -emergent Adverse Event TESAE Treatment -emergent Serious Adverse Events TTP Time to Progression ULN Upper limit of normal VC Vital Capacity WBC White blood cell WHO World Health Organization Aduro Biotech, Inc. CONFIDENTIAL Protocol ADU -CL-02 Final Version 1 Page 7 of 24 04MAY2018 1. INTRODUCTION AND OBJ ECTIVES OF ANALYSIS 1.1. Introduction ADU- CL-02 is a phase 1b, multicenter, open- label study in adults with malignant pleural mesothelioma (MPM) who are not eligible for curative surgery. The study consists of two cohorts which received CRS- 207 in combination with pemetrexed and cisplatin chemotherapy (Cohort 1) or low -dose cyclo phosphamide (Cy) prior to each CRS -207 infusion (Cohort 2). The study is intended to determine the safety of CRS -207 (with or without Cy) when administered in combination with pemetrexed and cisplatin and to evaluate the induction of immune response to mesothelin. 1.2. Objectives of the Abbreviated Statistical Analysis Plan (ASAP) This is an abbreviated statistical analysis plan ( ASAP) designed to outline the methods to be used in the analysis of study data for the abbreviated final analysis. The derivation and analysis of selected immunological / tumor marker endpoints will be discussed in another standalone document. The statistical analyses and summary tabulations described in this A SAP will provide the basis for the abbreviated reporting of the final anal ysis results from this trial . Populations for analysis, data handling rules, statistical methods, changes from the study protocol , and formats for data presentation are provided. Aduro Biotech, Inc. CONFIDENTIAL Protocol ADU -CL-02 Final Version 1 Page 8 of 24 04MAY2018 2. STUDY OBJECTIVES 2.1. Primary Objectives To determine the safety of CRS -207 (with or without low -dose cyclophosphamide [Cy] given one day prior to CRS- 207) when administered in combination with pemetrexed and cisplatin and to evaluate the induction of immune response to mesothelin as measured by IFN -γ ELISPOT assay prior to treatment and at time points during and after treatment . 2.2. Secondary Objectives The secondary objectives are to evaluate: • Tumor response • Progression free survival • Time to progression • Overall survival • Predictive value of serum mesothelin for therapeutic response for each treatment regimen 2.3. Exploratory Objectives The exploratory objectives are to: • conduct immune subset analysis (e.g., CD4, CD8, T reg) and gene expression profiling of tumor tissue pre- and post -vaccination; • to assess induction of anti -mesothelin humoral immune response; • to measure tumor marker kinetics as biomarkers of tumor response; • evaluate the association between pulmonary function improvement and tumor response; • evaluate the relationship of tumor response to overall survival. This ASAP will not include the analysis of : immune response to mesothelin, predictive value of serum mesothelin; or any secondary and exploratory objectives. The analysis of mesothelin related objectives will be discussed in another standalone document. Aduro Biotech, Inc. CONFIDENTIAL Protocol ADU -CL-02 Final Version 1 Page 9 of 24 04MAY2018 3. STUDY DESIGN 3.1. Synopsis of Study D esign Up to 16 subjects were originally planned to be enrolled in this study. Up to an additional 44 subjects were then subsequently planned to be enrolled in this study (for a total of up to 60 subjects) to obtain additional safety, immune, and efficacy data. Subjects were enrolled into two mutually exclusive cohorts described below. Cohort 1: A total of 38 subjects receive d 2 prime vaccinations (PV) of CRS -207 (1 × 109 colony -forming units ( CFU) given intravenously (IV) 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 received an additional 2 infusions (boost vaccinations; BV) of CRS- 207 3 weeks apart. Subjects enrolled in Cohort 1 included the 16 subjects originally planned plus a minimum of the first 16 subjects additionally enrolled. Cohort 2: The remaining subjects enrolled ( 22 total) received CRS- 207 in combinati on with chemotherapy at the dose and schedule described above; however, these subjects also received low-dose Cy (200 mg/m2) over 30 minutes 1 day prior to each CRS -207 infusion (i.e., prior to each PV and BV infusion). All subjects were to return to the clinic 4 weeks after their 2nd boost vaccination for an End of Course (EOC) visit. Subjects then had follow- up visits 4 weeks after the EOC visit and every 8 weeks thereafter until treatment discontinuation. Subjects continued to receive maintenance vaccinations (MV) with (Cohort 1) or without Cy (Cohort 2) at each follow- up visit ( following their original schedule) if they were clinically stable and continued to meet dosing eligibility. Subjects could continue on treatment with radiographic disease progression if clinically stable and the investigator believed the treatment may be providing benefit. Subjects were to return to the clinic for follow -up approximately 4 weeks after their EOC visit and every 8 weeks thereafter until disease progression or the investigator determined the subject was no longer receiving benefit from treatment (if a subject continues treatment beyond progression). All subjects were to complete an End of Study ( EOS) visit no more than 4 weeks following the final dose of study medication or prior to receipt of other cancer -related treatment. Following participation in this study, subjects could consent to long- term follow -up in the ADU- CL-03 study , which would follow them every 3 months until death. Death was captured from public record for subjects who did not enroll in ADU -CL-03. To monitor initial safety of the sequential vaccine regimen, no more than one subject was enrolled per week for the first six subjects. If at any point during the study more than 33% of subjects , cumulat ive, experienced a dose limiting toxicity (DLT), the dose would have been lowered from 1 x 109 CFU to 3 x 108 CFU for all subsequent dosing with CRS- 207. Subjects already receiving treatment would have continued to receive CRS- 207 dosing at the lower dose and all subsequent subjects would have received CRS- 207 at the lower dose. Aduro Biotech, Inc. CONFIDENTIAL Protocol ADU -CL-02 Final Version 1 Page 10 of 24 04MAY2018 Subjects who withdr ew consent or were removed from study medication before completing at least two cycles of chemotherapy were considered dropouts and replaced at the discretion of the lead investigator, sponsor, and medical monitor. 3.2.