26 5.0 EXPERIMENTAL PROCEDURES ................................................................................................... 29 5.1 OVERVIEW: SCHEDULE OF TIME AND EVENTS ......................................................................... 29 5.2 STUDY PROCEDURES ........................................................................................................................ 36 5.2.1 Screening Period (28 days prior to first study dose) .............................................................. 36 5.2.2 Treatment Period ................................................................................................................... 38 5.2.3 Study Follow -up Period/End of Study (EOS) ........................................................................ 45 5.3 LABORATORY EVALUATIONS ....................................................................................................... 46 5.3.1 Immune Monitoring Assessments ......................................................................................... 46 5.3.2 Tumor Markers ...................................................................................................................... 47 5.3.3 Tumor Biopsy ........................................................................................................................ 48 5.3.4 Blood Cultures for CRS -207 Surveillance ............................................................................. 49 6.0 PROCEDURES FOR HANDLING AES AND SAES ....................................................................... 50 6.1 DEFINITION OF AN ADVERSE EVENT ........................................................................................... 50 6.2 DEFINITION OF A SERIOUS ADVERSE EVENT (SAE) ................................................................. 51 6.3 RECORDING AEs AND SAEs ............................................................................................................. 52 6.4 ASSESSMENT OF GRADE ................................................................................................................. 53 6.5 ASSESSMENT OF CAUSALITY ......................................................................................................... 54 6.6 REPORTING OF SAEs ......................................................................................................................... 55 6.7 FOLLOW -UP OF AEs AND SAEs ....................................................................................................... 57 6.8 ADVERSE EVENTS OF SPECIAL INTEREST .................................................................................. 57 6.8.1 Suspected Infection with CRS -207 or Listeria ...................................................................... 57 7.0 STUDY OR STUDY SITE TERMINATION AND SUBJECT DISCONTINUATION ................. 59 7.1 PREMATURE STUDY OR STUDY SITE TERMINATION ............................................................... 59 7.2 SUBJECT DISCONTINUATION ......................................................................................................... 59 7.2.1 Adverse Event ....................................................................................................................... 60 7.2.2 Intercurrent Illness ................................................................................................................. 60 7.2.3 Noncompliance ...................................................................................................................... 60 7.2.4 Refusal of CTM Administration ............................................................................................ 61 8.0 DATA COLLECTION AND PROCESSING AND STATISTICAL ANALYSIS .......................... 62 8.1 DATA COLLECTION AND PROCESSING ........................................................................................ 62 8.2 STATISTICAL ANALYSIS .................................................................................................................. 63 8.2.1 General Overview .................................................................................................................. 63 8.2.2 Populations of Interest ........................................................................................................... 63 8.2.3 Baseline Comparability ......................................................................................................... 63 8.2.4 Efficacy Analysis ................................................................................................................... 64 8.2.5 Safety Analysis ...................................................................................................................... 65 8.2.6 Pharmacokinetic Analysis ..................................................................................................... 65 8.2.7 Interim Analysis .................................................................................................................... 65 8.2.8 Sample Size ........................................................................................................................... 65 Aduro Biotech , Inc. Protocol ADU -CL-02-v8 CRS -207 with Pemetrexed and Cisplatin TABLE OF CONTENTS (continued) Page Version 8, 08 March 2018 Page xiv 9.0 CLINICAL STUDY ADMINISTRATION ........................................................................................ 67 9.1 INFORMED CONSENT AND AUTHORIZATION FOR USE AND DISCLOSURE OF PHI ...........