For scenario (1), the % DLT by prior was derived using the model solving for the probability, p୧ at the ith dose. logitሺ݌௜ሻൌlogሺߙଵሻ൅ߚଵlogሺdଵ୧dଵ∗൘ሻ The model can be re-written as follows. ݌௜ൌ1 1൅expቀെlogሺߙଵሻെߚଵlogሺdଵ୧dଵ∗൘ሻቁ Using the estimates in Section 1.2, ie, logሺߙଵሻൌെ 0.847 and ߚଵൌ1,݀ଵ∗ൌ800 mg , the prior probability of DLTs at dose 25, 80, 200, 400, and 800 mg is 0.01, 0.04, 0.1, 0.18, and 0.30, respectively. Table 2.2.1-1: Simulation Results of BLRM for Monotherapy ScenarioBMS- 986226 Dose (mg)25 80 200 400 800MTD Not Selected (%)Fitted Median MTD Toxicity Observed (%)Avg No. of Patients By prior% DLT 14 1 0 18 30 % MTD 0 0.9 9.9 61 28.2 0 698.7 17.3 18.2 # Pts 3.1 0.5 2.0 8.2 4.4 # DLTs 0 0 0.2 1.5 1.4 Flatter than the one by the prior% DLT 10 15 20 25 30 % MTD 3.9 11.9 22.2 38.5 16.9 6.6 510.4 22.4 17.4 # Pts 4.1 2.0 2.7 5.8 2.7 # DLTs 0.4 0.3 0.6 1.4 0.8 Narrow safety window% DLT 37 18 31 80 % MTD 0.4 7.9 40.7 49.8 0.2 1 443.4 23.2 18.3 # Pts 3.4 1.9 4.9 7.1 1.1 Revised Protocol No.: 04 Date: 31-May-2019 207 Approved 5.0 v Approved 1.0 v Clinical Protocol CA021002 BMS-986226 anti-ICOS Table 2.2.1-1: Simulation Results of BLRM for Monotherapy ScenarioBMS- 986226 Dose (mg)25 80 200 400 800MTD Not Selected (%)Fitted Median MTD Toxicity Observed (%)Avg No. of Patients # DLTs 0.1 0.1 0.9 2.2 0.9 All low% DLT 1 5 10 15 20 % MTD 0.1 0.8 5.4 39.2 54.3 0.2 925.1 13.9 18.4 # Pts 3.1 0.3 1.3 7.0 6.8 # DLTs 0 0 0.1 1.0 1.3 All high% DLT 45 50 60 75 80 % MTD 11.6 2.6 0.7 0.1 0 85 10.7 57.8 7.0 # Pts 5.2 1 0.26 0.6 0 # DLTs 2.3 0.5 0.1 0.5 0 % DLT, true DLT rate; % MTD, proportion of the dose selected as the MTD; # Pts, average number of participants by assuming 3 participants for skipped dose level where the true toxicity rate is below the target rate; # DLTs, average number of DLTs by assuming no DLT for skipped dose level where the true toxicity r ate is below th e target rate; Fitted MTD: fitted MTD at 30% as the targe t toxicity r ate; % tox icity observed, average proportion of DLTs given the doses were tried The average sample size in this simulation was obse rved to be no more than 20 participants. The results for the scenarios of narrow safety window and all high show how the EWOC principle limits the risk of exposing particip ants from a toxic dose level.