The targeted toxicity rate in this study is in the range of 16% to 33%. The boundary is similar to the toxicity boundary used by a rule-based design (ie, 3 + 3 design) in that a minimum is set at 16% (approximately 1 in 6) DLT rate and at a maximum at 33% (a pproximately 2 in 6) DLT rate. The use of the EWOC principle limits the risk of exposing participants in the ne xt cohort to an unsafe dose by ensuring the posterior probability of the DLT rate exceedi ng 33% at any dose is capped at 30%. Due to the nature of the dose escalation process, the exact number of participants to be treated at each dose level cannot be precisely determined. The maximum number of participan ts to be treated in Part A will be approx imately 30 for dose escalati on. However, simulation studies with various scenarios show that the expected number of DLT-evaluable participants is approximately 20 participants or less ( Appendix 10). While the BLRM/BLRM-Copula will use DLT information from the DLT period only, clinical assessment will take into co nsideration the totality of available data, including PK/PD from all treated participants encompassing monotherapy and combination therapy, in assigning a dose level for the next cohort of 3 participants. At most, 12 D LT-evaluable participants will be treated at each dose level. Additional participants (up to a total of 12) may be treated at or any dose level below the estimated MTD for further evaluation of safety, PK, or PD parameters as required. The model-recommended MTD is the dose that satisfies the following 3 conditions:1) The empirical posterior probability that the “DLT rate of 1 6% to < 33%” is greater than a prespecified v alue (ie, 50%); 2) This probability needs to be the largest among the dose levels that satisfy the EWOC condition (ie, the probability that the “DLT rate > 33%” must be less than 30%); 3) The minimum number of participants (ie, 6 participants) was treated at this dose level. Revised Protocol No.: 04 Date: 31-May-2019 147 Approved 5.0 v Approved 1.0 v Clinical Protocol CA021002 BMS-986226 anti-ICOS The final recommended MTD/RP2D will be based on the recommendation from the BLRM/BLRM-Copula and the overall assessment of all available safety, PK/PD, and efficacy data. Lower doses of BMS-986226 may be tested if none of the planned doses are found to be tolerable as monotherapy or in combination with either nivolumab or ipilimumab. Such decisions will be made after discussion and agreement between the investigators and the BMS Medi cal Monitor/Study Director (or designee). 10.1.2 BMS-986226 and Nivolumab or Ipilimumab Combination Therapy Cohorts (Parts B and C) The purpose of the combination cohort phase of the study is to gather safety, tolerability, preliminary efficacy, PK, and PD information regarding BMS-986226 in combination with either nivolumab (Parts B) or ipilimumab (Parts C). For each dose level of the Parts B1 and C1, approximately 6 evaluable participants will be treated. This sample size also provides each dose level in Parts B1 and C1 with about 80% probability to detect any AE with an event rate of 24%. Approximately 6-12 evaluable participants may be treated at each dose level for Parts B2 (BMS-986226 + nivolumab) and C2 (BMS-986226 + ipilimumab) if additional safety , PD, or PD data is required to optimize dose and/or schedule selection. With up to 12 evaluable participant in each of Parts B2 and C2, it provides each dose level with up to 96% probability to detect any AE with an event rate of 24%. Once the safety (during the DLT evaluation) of a combination of BMS-986226 and nivolumab (ipilimumab) has been established and a recommended BMS-986226 dose regimen has been selected for Part D (E), additional participants (up to 6 additional e valuable participants for each of nivolumab and ipilimumab in combination with BMS-986226) may be treated at the recommended dose to better characterize the safety, PK, and PD profile. During this part of the study, the BLRM-Copula model, incorporating single-agent toxicity profiles of both BMS-986226 (Part A) and nivolumab or ipilimumab , as well as any available information from the combination cohorts, will be used to guide any potential dose recommendation. Details regarding the BLRM-Copula model are given in Appendix 10. 10.1.3 Combination Expansion Arms (Parts D and E) Approximately 40 evaluable participants will be treated in each of Parts D and E. This sample size provides each cohort with about 87% probab ility to detect any AE with an event rate of 5%. 10.2 Populations for Analyses For purposes of analysis, the following populations are defined: Population Description Enrolled All participants who have signed an ICF and are registered into the IRT Treated All participants who received any dose of study treatment Response-evaluable All treated participants with measurable disease at baseline and 1 of the following: (1) at least 1 postbaseline tumor assessment, (2) clinical progression, or (3) death. Pharmacokinetic All treated participants who have evaluable concentration-time data. Revised Protocol No.: 04 Date: 31-May-2019 148 Approved 5.0 v Approved 1.0 v Clinical Protocol CA021002 BMS-986226 anti-ICOS Population Description Immunogenicity All treated participants who have a baseline and at least 1 postbaseline immunogenicity measurement. Abbreviations: ICF = informed consent form; IRT = Interactive Response Technology.