For secondary analyses and related publications, author list and author order may vary from primary to reflect additional contributions. Revised Protocol No.: 04 Date: 31-May-2019 173 Approved 5.0 v Approved 1.0 v Clinical Protocol CA021002 BMS-986226 anti-ICOS APPENDIX 3 ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS: DEFINITIONS AND PROCEDURES FOR RECORDING, EVALUATING, FOLLOW UP AND REPORTING ADVERSE EVENTS Adverse Event Definition: An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation par ticipant administered study treatment and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (such as an abnormal laboratory finding), symptom, or disease temporally associated with the use of study treatment, whether or not considered related to the study treatment. Events Meeting the AE Definition •Any abnormal laboratory test results (hemato logy, clinical ch emistry, or uri nalysis) or results from other safety assessments (eg, ECG, radiological scans, vital signs measurements), including those that worsen from baseline, considered clinically significant in the medical a nd scientific judgment of the investigator. Note that abnormal lab tests or other safety assessments should only be reported as AEs if the final diagnosis is not available. Once the final diagnosis is known, the reported term should be updated to be the diagnosis. •Exacerbation of a chronic or intermittent pre-exis ting condition including either an increase in frequency and/or intensity of the condition. •New conditions detected or diagnosed after study intervention administration even though it may have been present before the start of the study. •Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction. •Signs, symptoms, or the clinical sequelae of a suspected overdose of either study intervention or a concomitant medication. Overdose, as a verbatim term (as reported by the investigator), should not be reported as an AE/SAE unless it is an intentional overdose taken with possible suicidal/self-harming intent. Such overdoses should be reported regardless of sequelae and should specify "intentional overdose" as the verbatim term Events NOT Meeting the AE Definition •Medical or surgical procedure (eg, endoscopy, appendectomy): the condition that leads to the procedure is the AE. •Situations in which an untoward medical occ urrence did not occur (so cial and/or convenience admission to a hospital). Revised Protocol No.: 04 Date: 31-May-2019 174 Approved 5.0 v Approved 1.0 v Clinical Protocol CA021002 BMS-986226 anti-ICOS DEFINITION OF SAE If an event is not an AE per definition above, th en it cannot be an SAE even if serious conditions are met. SERIOUS ADVERSE EVENTS Serious Adverse Event (SAE) is defined as any untoward medical occurrence that, at any dose: Results in death Is life-threatening (defined as an event in which the participant was at risk of death at the time of the event; it does not refer to an event which hypothetically might have caused death if it were more severe) Requires inpatient hospitalization or causes prolongation of existing hospitalization (see NOTE below) NOTE: The following hospitalizations are not cons idered SAEs in BMS clinical studies: •a visit to the emergency room or other hospital department < 24 hours, that does not result in admission (unless considered an important medical or life-threatening event) •elective surgery, planned prior to signing consent •admissions as per protocol for a planned medical/surgical procedure •routine health assessment requiring admission fo r baseline/trending of health status (e.g., routine colonoscopy) •medical/surgical admission other than to remed y ill health and planned prior to entry into the study. Appropriate documentation is required in these cases •admission encountered for another life circumstance that carries no bearing on health status and requires no medical/surgical intervention (e.g., lack of housing, economic inadequacy, caregiver respite, family circumstances, administrative reason) •admission for administration of anticancer therapy in the absence of any other SAEs (applies to oncology protocols) Results in persistent or significant disability/incapacity Is a congenital anomaly/birth defect Revised Protocol No.: 04 Date: 31-May-2019 175 Approved 5.0 v Approved 1.0 v Clinical Protocol CA021002 BMS-986226 anti-ICOS Is an important medical event (defined as a med ical event(s) that may not be immediately life- threatening or result in death or hospitalization but, based upon appropriate medical and scientific judgment, may jeopardize the particip ant or may require intervention [e.g., medical, surgical] to prevent one of the other serious outcomes listed in the definition above.) Examples of such events include, but are not limited to, intensive tr eatment in an emergency room or at home for allergic bronchospasm; blood dyscrasias or co nvulsions that do not result in hospitalization.) Potential drug indu ced liver injury (DILI) is also considered an important medical event. (See Section 9.2.7 for the definition of potential DILI.) Pregnancy and potential drug induced liver injury (DILI) must follow the same transmission timing and processes to BMS as used for SAEs (see section 9.2.5 for reporting pregnancies).