APPENDIX 6 MANAGEMENT ALGORITHMS FOR IMMUNO-ONCOLOGY AGENTS ................................................................................................................. APPENDIX 7 EASTERN COOPERATIVE ONCOLOGY GROUP (ECOG) PERFORMANCE STATUS ................................................................................... APPENDIX 8 CONSORT PUBLISHING REQUIREMENTS ................................... APPENDIX 9 NEW YORK HEART ASSOCIATION (NYHA) FUNCTIONAL CLASSIFICATION ................................................................................................ APPENDIX 10 STATISTICAL METHODOLOGY ................................................... APPENDIX 11 PROSTATE CANCER WORKING GROUP 3 (PCWG3) GUIDELINES (WITH MODIFIED RESPONSE EVALUATION CRITERIA IN SOLID TUMORS (RECIST) CRITERIA FOR SOFT TISSUE LESION ASSESSMENT) ...................................................................................................... APPENDIX 12 REVISED PROTOCOL SUMMARY OF CHANGE HISTORY ...... 147 147 147 147 148 148 148 149 149 150 150 152 154 157 158 166 174 178 181 193 201 202 203 204 221 229Clinical Protocol BMS-986226CA021002 anti-ICOS Revised Protocol No.: 04Date: 31-May-2019 9 Approved 5.0 v Approved 1.0 v Clinical Protocol CA021002 BMS-986226 anti-ICOS 1 SYNOPSIS Protocol Title: A Phase 1/2 Dose Escalation and Combination Cohort Study to Evaluate the Safety and Tolerability, Pharmacokinetics, and Efficacy of BMS-986226 (anti-ICOS mAb) Alone or in Combination with Nivolumab or Ipilimumab in Patients with Advanced Solid Tumors Study Phase: 1/2 Rationale: Subsequent to the approval of cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) and programmed death-1 (PD-1) pathway-blocking agents as anti-tumor therapies, the field of tumor immunotherapy is expanding rapidly. In addition to blocking co-inhibitory pathways, activating co-stimulatory pathways with the goal of potentiating anti-tumor immune responses are now considered a promising additional approach.