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J Clin Oncol 2016;34:1402-18 Revised Protocol No.: 04 Date: 31-May-2019 156 Approved 5.0 v Approved 1.0 v Clinical Protocol CA021002 BMS-986226 anti-ICOS 12 APPENDICES Revised Protocol No.: 04 Date: 31-May-2019 157 Approved 5.0 v Approved 1.0 v Clinical Protocol CA021002 BMS-986226 anti-ICOS APPENDIX 1 ABBREVIATIONS AND TRADEMARKS Term Definition 5-FU 5-fluorouracil AE adverse event ADA anti-drug antibody ADT androgen deprivation therapy AI accumulation index AIDS acquired immunodeficiency syndrome ALK anaplastic lymphoma kinase ALT alanine aminotransferase ALP alkaline phosphatase ANC absolute neutrophil count APC antigen presenting cell AST aspartate aminotransferase AT aminotransaminases AUC area under the concentration-time curve AUC(0-xh) area under the concentration-time curve from time zero to x hours AUC(0-T) area under the concentration-time curve from time zero to the time of the last quantifiable concentration AUC(TAU) area under the concentration-time curve in one dosing interval BICR blinded independent central review β-HCG beta-human chorionic gonadotrophin BID bis in die, twice daily BLRM Bayesian Logistic Regression Model BLRM-RD Bayesian Logistic Regression Model-Recommended Dose BMS Bristol-Myers Squibb BOR best overall response BSC best supportive care BTLA B- and T-lymphocyte attenuator BUN blood urea nitrogen C Cycle Revised Protocol No.: 04 Date: 31-May-2019 158 Approved 5.0 v Approved 1.0 v Clinical Protocol CA021002 BMS-986226 anti-ICOS Term Definition CA19-9 cancer antigen 19-9 Css-avg average concentration over a dosing interval (AUC[TAU]/tau) CBC complete blood count CC cervical cancer CD cluster of differentiation CEA cancer embryonic antigen Cexpected-tau expected concentration in a dosing interval CFR Code of Federal Regulations CI confidence interval CL total plasma clearance CLT total body clearance Cmax maximum observed plasma concentration Cmaxss steady state peak concentration Cmin minimum observed plasma concentration CMV cytomegalovirus CNS central nervous system CONSORT Consolidated Standards of Reporting Trials CR complete response CRC colorectal cancer CrCl creatinine clearance CRF Case Report Form, paper or electronic CRP C-reactive protein CT computerized tomography Ctau concentrations at the end of dosing interval CTC Common Toxicity Criteria CTCAE Common Terminology Criteria for Adverse Events CTLA-4 cytotoxic T lymphocyte-associated antigen-4 Ctrough trough observed plasma concentration CV coefficient of variation Dd ay Revised Protocol No.: 04 Date: 31-May-2019 159 Approved 5.0 v Approved 1.0 v Clinical Protocol CA021002 BMS-986226 anti-ICOS Term Definition DLT dose-limiti ng toxicity DMC Data monitoring committee DNA deoxyribonucleic acid DOR duration of response DTIC dacarbazine EC Ethics Committee ECG electrocardiogram ECOG Eastern Cooperative Oncology Group eCRF Electronic Case Report Form GFR glomerular filtration rate EGFR epidermal growth factor receptor EOI end of infusion EOT end of treatment eSAE electronic serious adverse event EU European Union EWOC escalation with overdose control F bioavailability FcγRs Fc gamma receptors FDA Food and Drug Administration FDG-PET fluorodeoxyglucose-positron emission tomography FFPE formalin-fixed paraffin embedded FIH first-in-human FITC fluorescein isothiocyanate FNR false-negative rate FPR false-positive rate FSH follicle-stimulating hormone FU Follow-up GGT gamma-glutamyl transferase GI gastrointestinal Revised Protocol No.: 04 Date: 31-May-2019 160 Approved 5.0 v Approved 1.0 v Clinical Protocol CA021002 BMS-986226 anti-ICOS Term Definition GLP Good Laboratory Practice GPVE Global Pharmacovigilance and Epidemiology hCG human chorionic gonadotropin HIV human immunodeficiency virus HLA-DR human leukocyte antigen - antigen D related HNSCC head and neck squamous cell carcinoma HNSTD highest non-severely toxic dose HPV human papillomavirus HR heart rate HRT hormone replacement therapy IB Investigator’s Brochure ICF informed consent form ICH International Conference on Harmonisation ICOS Inducible T-cell COStimulator ICOS-L Inducible T-cell COStimulator ligand IFN-γ interferon gamma Ig immunoglobulin IHC immunohistochemistry IL interleukin IMAE immune-mediated adverse event IMP investigational medicinal product I-O immuno-oncology Ipi ipilimumab IP investigational product irAE Immune-related adverse event irPR immune-related partial response irSD immune-related stable disease IRT Interactive Response Technology IV intravenous IVRS Interactive Voice Response System Revised Protocol No.: 04 Date: 31-May-2019 161 Approved 5.0 v Approved 1.0 v Clinical Protocol CA021002 BMS-986226 anti-ICOS Term Definition KLH keyhole limpet hemocyanin KRAS Kirsten rat sarcoma LDH lactate dehydrogenase mAb monoclonal antibody MAD maximum administered dose MAD-1 one dose level below the maximum administered dose mCRPC metastatic castration-resistant prostate cancer mDOR median duration of response MEL melanoma MMR mismatch repair mOS median overall survival MRI magnetic resonance imaging MRSD maximum recommended starting dose MSI microsatellite instability MTD maximum tolerated dose mWHO modified World Health Organization N number of participants or observations N1 + I3 nivolumab 1 mg/kg + ipilimumab 3 mg/kg N3 + I1 nivolumab 3 mg/kg + ipilimumab 1 mg/kg N/A not applicable NaF sodium fluoride NCI National Cancer Institute NK natural killer NOAEL no-observed-adve rse-effect level NSCLC non-small cell l ung cancer NCSLC-AD non-small cell l ung carcinoma-adenocarcinoma cell type NSCLC-SQC non-small cell l ung carcinoma, squamous cell type ORR objective response rate OS overall survival Revised Protocol No.: 04 Date: 31-May-2019 162 Approved 5.0 v Approved 1.0 v Clinical Protocol CA021002 BMS-986226 anti-ICOS Term Definition PBMC peripheral blood m ononuclear cells PCR polymerase chain reaction PD pharmacodynamics PD-1 programmed death-1 p-DILI potential drug-induced liver injury PD-L1 programmed death ligand-1 PE physical examination PET positron emission tomography PFS progression-free survival PFSR progression-free survival rate PID participant identification number PK pharmacokinetic(s) PPK population pharmacokinetics PR partial response PRC adenocarcinoma of the prostate PSA prostate-specific antigen PT preferred term Q1W once every week Q2W every 2 weeks Q3W every 3 weeks Q4W every 4 weeks Q8W every 8 weeks Q12W every 12 weeks R&D Research and Development RCC renal cell carcinoma RD recommended dose RE receptor expression Revised Protocol No.: 04 Date: 31-May-2019 163 Approved 5.0 v Approved 1.0 v Clinical Protocol CA021002 BMS-986226 anti-ICOS Term Definition RECIST Response Evaluation Criteria In Solid Tumors RNA ribonucleic acid RO receptor occupancy RP2D Recommended Phase II dose R/R resistant/recurrent RT-qPCR quantitative real-time polymerase chain reaction SAE serious adverse event SD stable disease SOC system organ class SPECT single photon emission computed tomography Std. Dev. standard deviation T3 triiodothyronine T4 thyroxine TBD to be determined T-cell T lymphocyte cell Teff T-effector cell TGI tumor growth inhibition T-HALF apparent terminal half-life in serum T-HALFeff effective elimination half-life that explains the degree of accumulation observed for a specific exposure measure (exposure measure includes AUC[TAU], Cmax, and Ctau) TIL tumor-infiltrating lymphocytes TKI tyrosine kinase inhibitor Tmax time of maximum observed plasma concentration TNBC triple-negative breast cancer Treg T-regulatory TSH thyroid-stimulating hormone T-VEC talimogene laherparepvec UCC urothelial carcinoma ULN upper limit of normal Revised Protocol No.: 04 Date: 31-May-2019 164 Approved 5.0 v Approved 1.0 v Clinical Protocol CA021002 BMS-986226 anti-ICOS Term Definition US United States WBC white blood cell WHO World Health Organization WOCBP women of childbearing potential Revised Protocol No.: 04 Date: 31-May-2019 165 Approved 5.0 v Approved 1.0 v Clinical Protocol CA021002 BMS-986226 anti-ICOS APPENDIX 2 STUDY GOVERNANCE CONSIDERATIONS The term ‘Participant’ is used in the protocol to refer to a person who has consented to participate in the clinical research study. The term ‘Subject’ used in the CRF is intended to refer to a person (Participant) who has consented to participate in the clinical research study.