2 LIST OF ABBR EVIATIONS ............................................................................................... 5 AMENDMENT HISTORY ................................................................................................... 8 1 STUDY DETAILS ........................................................................................... 10 1.1 Study objectives................................................................................................ 10 1.1.1 Primary object ives............................................................................................ 10 1.1.2 Secondary object ives........................................................................................ 11 1.1.3 Safety objectives............................................................................................... 12 1.1.4 Exploratory objectives ...................................................................................... 12 1.2 Study design ..................................................................................................... 12 1.3 Number o f patients ........................................................................................... 18 2 ANALYSIS SETS ............................................................................................ 20 2.1 Definit ion of analysis sets ................................................................................. 20 2.2 Violations and deviat ions.................................................................................. 22 3 PRIMARY AND SECONDAR Y VARIABLES ............................................... 27 3.1 Derivat ion of visit tumor responses ................................................................... 27 3.1.1 Derivat ion of RECIST 1.1 visit responses ......................................................... 27 3.1.1.1 Target l esions (TLs) –site Invest igator data ...................................................... 28 3.1.1.2 Non-target l esions (NTLs) and new lesio ns –site Investi gator data. .................. 33 3.1.1.3 Overall visit response –site Invest igator data .................................................... 34 3.2 Efficacy Variables ............................................................................................ 35 3.2.1 Object ive response rate (ORR) .......................................................................... 35 3.2.2 Progression -free survival (PFS) ........................................................................ 35 3.2.3 Overall Survival (OS) ....................................................................................... 37 3.2.4 Durati on of response (DoR) .............................................................................. 38 3.2.5 Best objective response (BoR) .......................................................................... 38 3.2.6 Disease control rate (DCR) ............................................................................... 39 3.2.7 Proporti on alive and progression free at 12 (APF12) and 18 (APF18) months ...39 3.2.8 Overall survival at 12 (OS12) and 24 (OS24) months ........................................ 39 3.3 Safety Variables................................................................................................