Similar graphs will also be produced for the BMS-986226 monotherapy. When recommending the next dose level, the model will first exclude doses that are intolerable (with overdosing probabilities > 30%, the rate that has been specified for BMS-986226 in combination with ipilimumab). Among those qualified candidate doses that are considered “tolerable”, the model will select the dose that maximizes the probability of being within the target toxicity range (DLT rate of 16% up to 33%). As illustrated in Figure 3-2, when there is 0 DLT observed out of 3 subjects for the dose level 25 mg and 1 DLT out of 3 subjects for the dose level 80 mg, the distribution of predicted DLT rates will be characterized into possibilities falling into 3 different categories. First, dose levels of 400 mg and 800 mg for BMS-986226 are excluded according to the higher-than-cutoff (0.3 for mono therapy) overdosing probabilities. Among the remainder of tolerable dose levels ( 25, 80, and 200 mg), the BLRM- Copula model reco mmends the dose that maximizes the probability of being within the target dosing interval. Ther efore, the model’s recommendation would be to escalate to 200 mg, which is associated with the highest target dosing probability of 0.372 compared with that of 80 mg (0.311). Similarly (although not shown on Figure 3-2), according to the rules specified above, the model could possibly recommend to de-escalate to a lower dose level than current treated dose level, extend the current dose level, or even recommend to stop and identify a new dose level lower than 80 mg, the lowest pre-specified dose lev el. Please refer to description of Figure 3-1 for details on how to specify the new dose levels. Revised Protocol No.: 04 Date: 31-May-2019 211 Approved 5.0 v Approved 1.0 v Clinical Protocol CA021002 BMS-986226 anti-ICOS Figure 3-3: Updated Box Plot after Incorporating Prior Information and All Previous DLT Information up to BMS-986226 80 mg for Pre-specified Dose Levels Interpretation and usage of Figure 3-3: Figure 3-3 is a snapshot with DLT information available at dose level 80 mg for the combination setting. The dose-DLT distributions calculated from the posterior samples of the model par ameters are characterized in the format of b oxplots for the pre-specified dose levels. This fi gure will be updated each time when there is new DLT informat ion available.