Do not make unauthorized copies. TABLE OF CONTENTS TABLE OF CONTENTS ............................................................................................................... 2 ABBREVIATIONS ........................................................................................................................ 4 INTRODUCTION ............................................................................................................ 5 STUDY RATIONALE ..................................................................................................... 5 OBJECTIVES ................................................................................................................. 6 Primary ob jective(s) .................................................................................................... 6 Secondary objective(s) ............................................................................................... 6 END POINTS .................................................................................................................. 6 Primary Endpoint ........................................................................................................ 6 Secondary Endpoint .................................................................................................... 6 STUDY DESIGN ............................................................................................................. 7 SCHEDULE OF ASSESSME NTS .................................................................................. 8 SAMPLE SIZE JUSTIFIC ATION ................................................................................... 9 Definition of Progression Free Survival (PFS) ............................................................ 9 ANALYSIS POPULATIONS ........................................................................................ 10 Efficacy Analyses ...................................................................................................... 10 8.1.1 Pr imary Efficacy Analysis .................................................................................. 10 8.1.2 Secondary Efficacy Analyses ............................................................................ 10 8.1.3 Sensitivity Analyses of the Primary Endpoint..................................................... 11 8.1.4 Sensitivity Analysis of Overall Survival .............................................................. 11 8.1.5 Subgroup Analyses of the Primary (PFS) and Key Secondary Endpoints (OS, ORR) 11 Safety Analyses ........................................................................................................ 12 Interim Analysis .........................................................................................................