9 2.1 PRIMARY OBJECTIVE ......................................................................................................................... 9 2.2 SECO NDARY OBJECTIVES ................................................................................................................. 9 2.3 EXPLORATORY OBJECTIVES ............................................................................................................ 9 3.0 STUDY DESIGN .................................................................................................................................. 10 3.1 BASIC DESIGN CHARACTERISTICS ............................................................................................... 10 3.2 STUDY POPULATION ........................................................................................................................ 12 3.2.1 Inclusion Criteria ................................................................................................................... 12 3.2.2 Exclusion Criteria .................................................................................................................. 13 3.2.3 Dosing Eligibility .................................................................................................................. 16 3.3 ENDPOINTS ......................................................................................................................................... 17 3.3.1 Primary Endpoint ................................................................................................................... 17 3.3.2 Secondary Endpoints ............................................................................................................. 17 3.3.3 Exploratory Endpoints ........................................................................................................... 17 3.4 RANDOMIZATION AND BLINDING ................................................................................................ 18 3.5 REPLACEMENT OF DROPOUTS ....................................................................................................... 18 3.6 DOSE -LIMITING TOXICITIES ........................................................................................................... 18 4.0 DRUGS AND DOSAGES .................................................................................................................... 20 4.1 IDENTIFICATION AND DESCRIPTION OF CLINICAL TRIAL MATERIAL (CTM) ................... 20 4.1.1 CTM ...................................................................................................................................... 20 4.1.2 Labeling ................................................................................................................................. 21 4.2 DOSING INSTRUCTIONS AND SCHEDULE .................................................................................... 21 4.2.1 Cyclophosphamide ................................................................................................................ 21 4.2.2 CRS -207 ................................................................................................................................ 21 4.2.3 Pemetrexed ............................................................................................................................ 23 4.2.4 Cisplatin ................................................................................................................................. 23 4.2.5 Delaye d Dosing ..................................................................................................................... 24 4.3 STORAGE AND HANDLING OF CLINICAL TRIAL MATERIAL .................................................. 24 4.3.1 Cyclophosphamide ................................................................................................................ 24 4.3.2 CRS -207 ................................................................................................................................ 25 4.3.3 Environmental Precautions .................................................................................................... 25 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 xiii 4.4 PRODUCT ACCOUNTABILITY ......................................................................................................... 26 4.5 PRIOR, CONCOMITANT, AND EXCLUDED THERAPY ................................................................