SUMMARY OF KEY CHANGES FOR REVISED PROTOCOL 02 Section Number & Title Description of Change Brief Rationale Table 2-1: Screening Procedural Outline (CA021002); Table 9.4.4-1; Clinical New information about a tetanus booster to be administered for all participants in Parts A, B, and C Revised Protocol No.: 04 Date: 31-May-2019 231 Approved 5.0 v Approved 1.0 v Clinical Protocol CA021002 BMS-986226 anti-ICOS SUMMARY OF KEY CHANGES FOR REVISED PROTOCOL 02 Section Number & Title Description of Change Brief Rationale Laboratory Tests; Section 4 Objectives and Endpoints; Section 5.1.2 Treatment phase; Section 5.1.5 Treatment Beyond Progression; Section 6.1. Inclusion Criteria; Section 8.1 Discontinuation from Study Treatment; Section 8.1.2 Treatment Beyond Disease Progression; Section 8.1.3 Discontinuation Due to Further Progression (Confirmed Progression); Section 9.1 1 Method of Assessment; Section 9.1.3 Secondary Efficacy Assessments; Section 10.3 Statistical Analyses; Added text to refer to Prostate Cancer Working Group 3 (PCWG 3) efficacy assessment criteria for prostate.Modified efficacy assessment criteria to include PCWG 3 criteria in addition to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria. Revised Protocol No.: 04 Date: 31-May-2019 232 Approved 5.0 v Approved 1.0 v Clinical Protocol CA021002 BMS-986226 anti-ICOS SUMMARY OF KEY CHANGES FOR REVISED PROTOCOL 02 Section Number & Title Description of Change Brief Rationale Table 2-2 On-treatment Procedural Outline (CA021002); Table 2-5: Retreatment and Extended Treatment Procedural Outline (CA021002); Section 5 Study design; Section 5.1 Overall Design; Section 5.1.2.2 BMS-986226 and Nivolumab Combination Therapy Cohort (Parts B1 and B2); Section 5.1.2.3 BMS-986226 and Ipilimumab Combination Therapy Cohort (Parts C1 and C2); Section 6.1 Inclusion Criteria; Section 7.1 Treatment Administered; Section 10.1.2 BMS-986226 and Nivolumab or Ipilimumab Combination Therapy Cohorts (Parts B and C)Revised the study design and the text in this section to modify the combination escalation of BMS-986226 with either nivolumab (Part B) or ipilimumab (Part C) to include and prioritize a Q12W dosing schedule that will provide pharmacodynamic data to inform dose and schedule.Prioritized BMS-986226 Q12W cohorts to determine optimal dose and schedule using selected assays including ICOS and ICOS-L expression Table 2-2 On-treatment Procedural Outline (CA021002); Table 2-5: Retreatment and Extended Treatment Procedural Outline (CA021002); Section 5 Study design; Section 5.1.2.4 Combination Expansion Arms (Parts D and E); Section 5.2 Number of Participants; Section 6.1. Inclusion Criteria; Section 7.1 Treatment Administered; Section 10.1.2 BMS-986226 and Nivolumab or Ipilimumab Combination Therapy Cohorts (Parts B and C)New text has been added or modified in these sections related to dose expansion phase with either nivolumab (Part D) or ipilimumab (Part E)Modification was made to align with the revised protocol study design. The purpose of the cohort expansion is to gather additional safety, tolerability, preliminary efficacy, PK, and PD information regarding BMS-986226 in combination with either nivolumab (Part D) or ipilimumab (Part E) Section 5.1.3.1 Safety Follow- up; Section 5.1.5.1 Retreatment During Response Follow-up; Section 5.4.2.2; Modified language to allow combination patients to receive study therapies for 2 years rather than 24 weeksModification was made to align with published data on the efficacy of treatment with nivolumab monotherapy for 2 years Revised Protocol No.: 04 Date: 31-May-2019 233 Approved 5.0 v Approved 1.0 v Clinical Protocol CA021002 BMS-986226 anti-ICOS SUMMARY OF KEY CHANGES FOR REVISED PROTOCOL 02 Section Number & Title Description of Change Brief Rationale Section 5.2 Number of ParticipantsTotal number of participants in this study was increased to 234 subjects. Modification was made to fulfill the expected number of participants per revised study design. Section 6 Inclusion criteria; Criteria 3d) Modified inclusion criteria for prostate cancer tumorModification was made to clarify prior hormonal and chemotherapies allowed and to define progression as per the PCWG3 criteria. Section 7.3.2 BMS-986226 Dose Limiting ToxicitiesThe dose-limiti ng toxicity (DLT) period was modified for the combination of BMS- 986226 + nivolumab (Part B1) or ipilimumab (Part C1) to allow patients to be DLT eligible after 1 dose of BMS-986226.The 5-week DLT period for Parts B and C covers 2 doses of nivolumab (Q4W) or ipilimumab (Q4W) and 1 dose of BMS-986226 (Q12W). Section 9.5 Pharmacokinetic and Immunogenicity Assessments.PK and immunogenicity sample scheduling tables for Parts A, B1, B2, C1 and C2 were modified to support the revised study design.