Date of issue Reason for update 1.0 03MAR2017 Initial version for REC/HRA and MHRA submission. 2.0 15MAY 2017 Revised version post initial review by the MHRA and REC. 3.0 18JUL2017 Revised version post 2nd review by the REC. 4.0 19NOV2018 Protocol Amendment 01: Clarification that the requirement for dose delays excludes AEs of ISR, amendment to the exclusion criteria regarding the use of prohibited concomitant steroid medication, amendment to when the expansion cohort can open, requirement for related AEs meeting the stopping rule criteria to be reported as an SAE added, caveat around the use of systemic steroids to treat AEs added, change in container closure system used for the IMP , clarification on imaging requirements and objectives , change to the lymphocyte count required for inclusion into the study . Other minor changes and clarifications. 5.0 08JUN2021 Protocol Amendment 02: Removal of the control arm in the safety cohort and removal of the expansion cohort; change to end of trial definition; changes to reasons for withdrawal; other minor changes and clarifications. CONFIDENTIAL CRUKD/17/003 Protocol Final 5.0 dated 08Jun2021 Page 3 of 72 EudraCT number : 2016 -002577 -35 Cancer Research UK TABLE OF CONTENTS TITLE PAGE TABLE OF CONTENTS LIST OF ABBREVIATIONS AND DEFINITION OF T ERMS PROTOCOL SIGNATURES 1 PROTOCOL SYNOPSIS ..................................................................................................... 12 1.1 Full t itle: ................................................................................................................................