B. Non-hepatic Non-hematological DLT Any of the following events will be considered a non-hepatic non-hematological DLT: •Any Grade 2 drug-related uveitis or eye pain or bl urred vision that does not respond to topical therapy and does not improve to Grade 1 severity ≤2 weeks orrequires systemic treatment. •Grade 3 drug-related uveitis, pneumonitis, bronchospasm, myocarditis, neurologic tox icity, hypersensitivity reaction, or infusion reaction of any duration will require discontinuation. •Any Grade 3 or greater nondermatolog ic, nonhepatic nonh ematologica l study treatment-related toxicity will be considered a DLT, with the following specific exceptions: −Grade 3 or Grade 4 electrolyte abnormalities that are not complicated by associated clin ical adverse experiences, last ≤72 hours, and either resolve spontaneously or respond to conventional medical intervention −Grade 3 nausea, vomiting, or diarrhea that lasts less than 72 hours (without steroid therapy) and either resolves spontaneously or responds to conventional medical intervention −Isolated Grade 3 elevation of amylase or lipase not associated with clinical or radiographic evidence of pancreatitis −Isolated Grade 3 fever not associated wi th hemodynamic compromise (eg, hypotension, clinical or laboratory evidence of impaired end-organ perfusion or with other symptoms of infusion-rel ated reactions that returns to ≤Grade 1 with standard treatment in ≤ ≤1 hour Revised Protocol No.: 04 Date: 31-May-2019 86 Approved 5.0 v Approved 1.0 v Clinical Protocol CA021002 BMS-986226 anti-ICOS −Grade 3 endocrinopathy that is well controlled by hormone replacement −Grade 3 tumor flare (defined as pain, irritati on, or rash that localizes to sites of known or suspected tumor) −Grade 3 fatigue for ≤7 days −Grade 3 infusion reaction that returns to Grade 1 in ≤1 hour C. Dermatologic DLT •Grade 3/4 rash if no improvement (ie, resolution to Grade ≤1) after a 1-week to 2-week infusion delay. Participants who have not e xperienced a Grade 3 drug-r elated skin AE may resume treatment in the presence of Grade 2 skin toxicity. •Grade 4 rash of any duration D. Hematologic DLT •Grade 4 neutropenia ≥5 days in duration •Grade 4 thrombocytopenia or Grade 3 thrombocytopenia with clinically significant bleeding or any requirement for platelet transfusion •Grade 4 anemia not explained by underlying disease •Grade 4 febrile neutropenia •Grade 3 febrile neutropenia that lasts > 48 hours •Grade ≥3 hemolysis (i.e., requiring transfusion or medical intervention such as steroids) 7.3.3 Management Algorithms for Immuno-oncology Agents Immuno-oncology (I-O) agents are associated with irAEs that can differ in severity and duration from AEs caused by other therapeutic classes. BMS-986226, nivolumab, and ipilimumab are considered I-O agents in this protocol.