• All identified non-serious AEs must be recorded and described on the non-serious AE page of the CRF (paper or electronic). Completion of s upplemental CRFs may be requested for AEs and/or laboratory abnormalities that are reported/identified during the course of the study. After the initial AE/SAE report, the investigator is required to proactively follow each participant at subsequent visits/contacts. All SAEs will be followed until resolution, until the c ondition stabilizes, until the event is otherwise explained, or un til the participant is lost to follow-up (as defined in Section 8.3 ). Further information on follow-up procedures is given in Appendix 3. 9.2.4 Regulatory Reporting Requirements for SAEs All SAEs that occur during the screening period and within 100 days of the last dose of st udy treatment must be collected. For participants randomized/assigned to treatment and never treated with study treatment, SAEs should be collected for 30 days from the date of randomization/tr eatment assignment. •Prompt notification by the investigator to the Sponsor of SAEs is essential so that legal obligations and ethical re sponsibilities toward the safety of participants and the safety of a product under clinical investigation are met. •An investigator who receives an investigator safety report describing SAEs or other specific safety information (eg, su mmary or listing of SAEs) from the Sponsor w ill file it along with the IB and will notify the Institutional Review Board/EC, if appropri ate accordi ng to local requirements. Sponsor or designee will be reporting AEs to regulatory authorities and EC according to local applicable laws including European Directive 2001/20/EC and FDA Code of Federal Regulations 21 CFR Parts 312 and 320. A suspected unexpected serious adverse reaction is a subset of SAEs and will be reported to the appropriate regulatory authorities and investigators following local and global guidelines and requirements. 9.2.5 Pregnancy If, following initiation of the study treatment, it is subsequently discovered that a participant is pregnant or may have been pregnant at the time of study exposure, including during at least 5 half-lives after product adminis tration, the investigator must immediately notify the BMS Medical Monitor/Study Di rector (or designee) of this event and comp lete and forward a Pregnancy Surveillance Form to BMS Designee within 24 hours of awareness of the event and in accordance with SAE reporting procedures described in Appendix 3. Revised Protocol No.: 04 Date: 31-May-2019 104 Approved 5.0 v Approved 1.0 v Clinical Protocol CA021002 BMS-986226 anti-ICOS In most cases, the study treatment w ill be permanently discontinued in an appropri ate manner (eg, dose tapering if necessary for participant safety). Please call the BMS Medical Monitor/Study Director (or designee) within 24 hours of awareness of the pregnancy. Protocol-required procedures for study discontinuation and follow-up must be pe rformed on the participant. Follow-up information regarding the course of the pregnancy, including perinatal and neonatal outcome and, where applicable, offspring information, must be reported on the Pregnancy Surveillance Form. Any pregnancy that occurs in a female partner of a male study participant should be re ported to the Sponsor or designee. For the Sponsor or designee to collect any pregnancy surveillance information from the female part ner, the female partner must sign an ICF for disclosure of this information. Information on this pregnancy will be collected on the Pregnancy Surveillance Form. 9.2.6 Laboratory Test Result Abnormalities The following laboratory test result abnormalities should be captured on the non-serious AE CRF page or electronic SAE Report Form, as appropri ate. Paper forms are only intended as a back-up option when the electronic system is not functioning. •Any laboratory test result that is clinically significant or meets the definition of an SAE •Any laboratory test result abnormality that required the participant to have study tr eatment discontinued or interrupted •Any laboratory test result abnormality that required the participant to receive specific corrective therapy It is expected that, wherever possible, the clinical rather than laboratory term would be used by the reporting investigator (eg, anemia versus low hemoglobin value). 9.2.7 Potential Drug-induced Liver Injury Wherever possible, ti mely confirmation of initial liv er-related laboratory abnormalities s hould occur prior to the reporting of a p-DILI event. A ll occurrences of p-DILIs, meeting the defined criteria, must be reported as SAEs (see Section 9.2.4 and Appendix 3 for reporting details). p-DILI is defined as: 1) Aminotransaminases (AT) (ALT or AST) elevation > 3 ×ULN AND 2) Total bilirubin > 2 ×ULN, without initial findings of cholestasis (elevated serum ALP), AND 3) No other immediately a pparent possible causes of AT elevation and hyperbilirubinemia, including, but not limited to, viral hepatitis, preexisting chronic or acute liver disease, or the administration of other drug(s) known to be hepatotoxic. Revised Protocol No.: 04 Date: 31-May-2019 105 Approved 5.0 v Approved 1.0 v Clinical Protocol CA021002 BMS-986226 anti-ICOS The key responsibilities for investigators during p-DILI assessment include the following: •Early detection, med ical evaluation (including the exclusion of other potential causes), and rapid laboratory confirmation of liver-related abnormalities •BMS notification of p-DILI cases via SAE forms Following the gathering and assessment of relevant clinical information, BMS is responsible for: •Timely evaluation and triaging of p-DILI cases •Expedited reporting of p-DILI cases •Expanded review of p-DILI cases, including a detailed assessment of all available clinical information, investigations, and biochemical data Investigators are expected to monitor ongoing routine and ad hoc hepatic laboratory test results to rapidly determine whether a participant meets p- DILI criteria. They are expected to promptly notify BMS of all p-DILI cases. p-DILI cases ma y be identified by abnorm al liver biochemistry values, whether or not they are accompanied by liver-related signs and/or symptoms. In both cases, expedited confirmation with repeat laboratory tes ting should occur within 3 business days using a hepatic laboratory panel (ALT, AST, total bilirubin, and ALP). Any participant with an abnormal hepatic laboratory panel th at meets p-DILI criteria is a candidate for study tr eatment discontinuation. Any confirmed p-DILI event must be reported (along with a description of the clinical findings) to BMS as an SAE within 24 hours of confirmation. An extensive clinical history examination and appr opriate investigations should be obtained to exclude cholestatic and other apparent causes that may explain the observed a bnormalities in liver function and/or hepatic signs and symptoms. Other apparent causes include, nonexhaustively and by way of example only, infectious diseases (such as active hepatitis A, B, and C), congenital diseases (such as Gilbert’s syndrome), neoplasti c diseases (such as hepatocellular carcinoma), autoimmune diseases (such as primary biliary cirrhosis), and the use of concomitant hepatotoxic medications (such as antibiotics, the oral contraceptive pill, and herbal medicines). All investigations to exclude poten tial causes of liver function abnormalities or he patic signs and/or symptoms should be guided by relevant factors su ch as the participant’s age, gender, clinical history, and signs and symptoms. 9.2.8 Other Safety Considerations Any significant worsening noted during interim or final physical examinations, ECG, x-ray filming, and any other potential safety assessment required or not required by protocol should also be recorded as a non-serious AE or SAE, as appropriate, and reported accordingly. 9.3 Overdose An overdose is defined as the accidental or intentional administration of any dose of a product that is considered both excessive and medically important. For this study, any dose of BMS-986226, nivolumab and/or ipilimumab, that is greater than the assigned dose, and considered excessive and medically important by the investigator, will be considered an overdose. Revised Protocol No.: 04 Date: 31-May-2019 106 Approved 5.0 v Approved 1.0 v Clinical Protocol CA021002 BMS-986226 anti-ICOS In the event of an overdose, the investigator/treating physician should: 1) Contact the Medical Monitor/St udy Director (or designee) immediately 2) Closely monitor the participant for AEs/SAEs and laboratory abnormalities until study treatment can no longer be detected systemically (at least 125 days) 3) Obtain a plasma sample for PK analysis within 125 days from the date of the last dose of study treatment if requested by the Medical Monitor/ Study Director (or designee) (determined on a case-by-case basis) 4) Document the quantity of the excess dose as w ell as the duration of the overdosing in the CRF. Decisions regarding dose interruptions or modifications will be made by the investigator in consultation with the Medical Monitor/Study Director (or designee) based on the clinical evaluation of the participant.