The between-trial variability is assumed to be moderate. Therefore, τ1 and τ2 were set to follow a log-normal distribution with mean lo g(0.25) and log(0.125) respectively with a common standard deviation log(2)/1.96. This leads to the MAP prior in Table 4.1.3-2 . To obtain the mixture prior, 50% weight is assigned to the MAP component, and 50% weight is assigned to the weakly informative component. The mixture prior is also presented in Table 4.1.3- 2. Note that the prior of Ipilimumab is derived us ing mg/kg-based Q3W hi storical data, and the reference dose was selected to be 10 mg/kg Q3W. Since the DLT-evaluation period is 5 weeks and to be conservative, we will keep the reference dose as is when evaluating Ipilimumab as Q4W in our current study. In other words, we conservati vely assume that the DLT toxicity profile in the DLT-evaluation period from Ip ilimumab Q4W is similar to that for the Ipilimumab Q3W from historical studies. Table 4.1.3-1: Data from Phase 2 and 3 Ipilimumab Studies at BMS in Participants with Previously Treated or Untreated Advanced Melanoma SourceDose of Ipilimumab (mg/kg*)Toxicity (percentage [number of participants/total participants])a Phase 3 study MDX010-20 3 20.6% (27/131) Phase 2 Studies Pooled 3 14.4% (16/111) 10 30.5% (99/325) CA184169 3 18.2% (66/362) 10 34.1% (124/364) CA184022 0.3 9.7% (7/72) 3 14.1% (10/71) 10 26.8% (19/71) a% of participants with treatment-related Grade 3-4 AEs Revised Protocol No.: 04 Date: 31-May-2019 218 Approved 5.0 v Approved 1.0 v Clinical Protocol CA021002 BMS-986226 anti-ICOS Table 4.1.3-2: Prior Distribution for Model Parameters of Ipilimumab Parameter: (log(α α3), log(β3)) Means Standard DeviationsCorrelation Prior for Ipilimumab (-0.827, -0.289) (1.444, 0.787) 0.009 MAP component (-0.805, -0.578) (0.276, 0.232) 0.263 Weakly Informative Prior (-0.847, 0) (2, 1) 0 Note: Ipilimumab prior information was based on mg/kg Q3W dosing. 4.1.4 Prior for Interaction Parameters for Joint Toxicity of BMS-986226 and Nivolumab or Ipilimumab Combination A gamma prior distribution for the interaction parameter γଵis derived to reflect the current uncertainty about the toxicity profile of the combination of BMS-986226 and nivolumab or ipilimumab. Although no PK drug-drug interaction is expected, the possib ility of a significant positive interaction between BMS-986226 and nivolumab or ipilimumab cannot be totally excluded. The interaction parameter γଵwas chosen accordingly but with a degree of uncertainty to allow for the possibility that the interaction may be positive or negative.