Participants not meeting guidelines for permanent discontinuation w ill be permitted to resume therapy based on the criter ia specified below in Section 7.3.5. Participants eligible to resume study treatment w ill resume study tr eatment at the nominal treatment visit following their last received study treatment dose. The end of cycle tumor assessments, such as CT, MRI, or positron emission tomography (PET), will conti nue on a once Q8W schedule relative to the participant’s first dose, regardless of any treatment delay incurred. 7.3.5 Exceptions to Permanent Discontinuation Criteria Any drug-related AE occurring at any time that meets DLT criteria as outlined in Section 7.3.2 will require permanent discontinuation. Exceptions to permanent discontinuation are listed in Section 8.1. Study treatment may be re-initiated in par ticipants experiencing non-life-threatening AEs that meet DLT criteria and that have been resolved to Grade 1 or baseline. Consideration to resume treatment will be made on a case-by-case basis in a discussion between the investigator and BMS Medical Monitor/Study Director (or design ee) and approval of the sponsor, taking into account the overall benefit/risk ratio for the individual participant and the following factors: •A 2-week washout period is required after completing the immune suppressive treatment used to manage the AE (eg, steroids). The AE should not recur/worsen during the washout period. •Evidence for clinical or radiographic benefit must be present, which can include improvement of physical symptoms (eg, ECOG status, shortness of breath), symptomatic improvement in combination with assessment of SD, or radiographic response. Revised Protocol No.: 04 Date: 31-May-2019 88 Approved 5.0 v Approved 1.0 v Clinical Protocol CA021002 BMS-986226 anti-ICOS In the event of recurrence of the AE that met the DLT criteria, study treatment will be permanently discontinued for the participant. Additionally, consideration to permanently discontinue study treatment for participants with any severe Grade 3 drug-related AE that recurs w ill be made on a case-by-case basis in a discussion between the investigator and BMS Medical Monitor/Study Director (or designee). All participants who discontinue IP should comply with protocol-specified follow-up procedures as outlined in Section 5.1.3 . The only exception to this requirement is when a participant withdraws consent for all study proce dures including post-treatment study follow-up or loses the ability to consent freely (eg, imprisonment or involuntarily incarceration for the tr eatment of either a psychiatric or physical illness). If study treatment is discontinued prior to th e participant’s completion of the study, the reason for the discontinuation must be documented in the participant’s medical records and entered on the appropriate Case Report Form (CRF) page. 7.3.6 Management of Drug-related Infusion Reactions BMS-986226 is a hu manized mAb and has the potential to induce hypersensitivity r eactions following administration. As of 28-March-2019, 7 of 19 (36.8%) participants treated with BMS-986226 monotherapy experienced a Grade 1 or Grad e 2 infusion-related reaction. One participant experienced Grade 3 hypersensitivi ty during BMS-986226 infusion after the data cut- off date of 28 March 2019. When such reactions occur, they may manifest with fever, chills, ri gors, headache, flushing, rash, urticaria, pruritus, arthralgia, hypotension, hypertension, bronchospasm, or other allergic-like r eactions. All Grade 3 or 4 i nfusion r eactions should be reported within 24 hours to the BMS Med ical Monitor/Study Dir ector (or designee) and reported as an SAE. Infusion reactions should be gra ded according to NCI CTCAE v4.03 27guidelines. Premedications are recommended as per section 7.1. Treatment recommendations for infusion reactions are provided below and may be modified based on local treatment s tandards and guidelines, as appropriate. For Grade 1 symptoms: Mild reaction; infusion inte rruption not i ndicated; intervention not indicated. •Remain at bedside and monitor participant until recovery from symptoms. The following prophylactic premedications are recommended for future infusions: diphenhydramine 50 mg (or equivalent) and acetaminophen/ paracetamol 325 to 1,000 mg at least 30 minutes before study treatment administrations. For Grade 2 symptoms: Moderate reaction requiring therapy or infusion interruption but responding promptly to symptomat ic treatment (eg, antihis tamines, nonsteroidal-anti-inflammatory drugs, narcotics, corticosteroids, bronchodilators, or IV fluids); prophylactic medications indicated for ≤24 hours. Revised Protocol No.: 04 Date: 31-May-2019 89 Approved 5.0 v Approved 1.0 v Clinical Protocol CA021002 BMS-986226 anti-ICOS •Remain at the bedside and monitor participant until resolution of symptoms .Monitor participant closely. •Stop the study treatment i nfusion, begin an IV infusion of normal saline, and tr eat the participant with diphenhydramine 50 mg IV (or equivalent) and acetaminophen/paracetamol 325 to 1,000 mg. •Corticosteroid and/or bronchodilator therapy may also be administered as appropriate. •If the infusion is interrupted, then restart the infusion at 50% of the original infusion rate when symptoms resolve; if no furt her complications ensue after 30 minutes, the rate may be increased to 100% of the original i nfusion rate. The amount of study tr eatment infused must be recorded on the CRF. •If symptoms recur, then no further BMS-986226, nivolumab, or ipilimumab will be administered at that visit. •For future infusions, the following prophylactic premedications are recommended: diphenhydramine 50 mg (or equivalent) a nd acetaminophen/paracetamol 325 to 1,000 mg should be administered at least 30 minutes before study treatment i nfusions. If n ecessary, corticosteroids (up to 25 mg of hydrocor tisone or equivalent) may be used. For Grade 3 or 4 symptoms: Severe reaction, Grade 3: prolonged (eg, not rapidly responsive to symptomatic medication and/or brief interruption of infusion); recurrence of symptoms following initial im provement; hospitalization indicated for other clinical sequelae (eg, renal impairment or pulmonary infiltrates); Grade 4: life-threatening; pressor or ventilatory support indicated. •Remain at bedside and monitor participant until recovery of the symptoms.