2) Log(ߙଵ) and log( ߚଵ) follow a bivariate normal distribution. Through those steps, the prior obtained is given in Table 1.2-1. Table 1.2-1: Prior Distribution for Model Parameters for BMS-986226 Parameter Means Standard Deviations Correlation log(ߙଵ), log(β1) (-0.847, 0) (1.53, 1) 0 This prior will be fitted into EAST®v6.3.1 Dose Escalatio n Module by Cytel for the Monotherapy Escalation of BMS-986226 as stated in model setup section. 2 DECISION RULE FOR DOSE ESCALATION AND SIMULATION Dose escalation recommendations for BMS-986226 monotherapy w ill be based on the inference from the Bayesian posterior and the probability that the true DLT rate for each dose lies in 1 of the following categories: •[0%, 16%) under-dosing •[16%, 33%) targeted toxicity •[33%, 100%] excessive toxicity Note: “[“ or “]“ is inclusive of the respective endpoint, and “(“ or “)”exclusive of the respective endpoint. These boundaries are similar to th e toxicity boundaries used by a rule-based design (ie, 3 + 3 design) in that a minimum is set at 16% (~ 1 in 6) DLT rate and a maximum at 33% (~ 2 in 6) DLT rate. Following the principle of EWOC, dose recommendations for the next cohort w ill be based on the Bayesian model after DLT information becomes available during the DLT peri od, accounting for all of the available data from the administered doses, and the candidate doses are the ones fulfilling the overdose criterion that there is less than 30% chance of excessive toxicity. Only the candidate doses w ill be considered for the next cohort. While the Bayesian model w ill use DLT information from the DLT period only, clin ical assessment w ill take into consideration of the totality of available data including pharmacokinetics (PK) /pharmacodynamics from all treated participants. Stopping Rules: The following is the general stopping rules of BLRM (-Copula) during Dose Escalation: •If all of 30 DLT evaluable participants are treated. Revised Protocol No.: 04 Date: 31-May-2019 205 Approved 5.0 v Approved 1.0 v Clinical Protocol CA021002 BMS-986226 anti-ICOS •If all of the current pre-specified doses are considered intolerable according to the pre-specified cutoff (ie, EWOC criteria), then the model will recommend stopping the current dose level anda new dose level lower than the current lowest dose level will need to be identified. •The maximum number of DLT-evaluable participan ts in a dose level will be 12.