15. references
appendix a performance status criteria

| ECOG Performance Status Scale Grade Descriptions Normal activity. Fully active, able to  0 carry on all pre-disease performance  without restriction. Symptoms, but ambulatory.  Restricted in physically strenuous  activity, but ambulatory and able to  carry out work of a light or sedentary  nature (e.g., light housework, office  work). 1 In bed <50% of the time. Ambulatory  and capable of all self-care, but unable  to carry out any work activities. Up  and about more than 50% of waking  hours. 2 In bed >50% of the time. Capable of  only limited self-care, confined to bed  or chair more than 50% of waking  hours. 3 100% bedridden. Completely  4 disabled. Cannot carry on any selfcare. Totally confined to bed or chair. 5 Dead.   |
|---|  
As published in Am. J. Clin. Oncol.: *Oken, M.M., Creech, R.H., Tormey, D.C., Horton, J., Davis, T.E., McFadden, E.T.,*
Carbone, P.P.: Toxicity And Response Criteria Of The Eastern Cooperative Oncology Group. Am J Clin Oncol 5:649655, 1982. The Eastern Cooperative Oncology Group, Robert Comis M.D., Group Chair APPENDIX B ABBREVIATIONS AND DEFINITION OF TERMS  
| The following abbreviations and special terms are used in this study Clinical Study Protocol. Abbreviation or  Explanation special term ADA Anti-drug antibody AE Adverse event AESI Adverse event of special interest ALK Anaplastic lymphoma kinase ALT Alanine aminotransferase APF12 Proportion of patients alive and progression free at 12 months from  randomization AST Aspartate aminotransferase BoR Best objective response BP Blood pressure C Cycle CD Cluster of differentiation CI Confidence interval CL Clearance Cmax Maximum plasma concentration Cmax,ss Maximum plasma concentration at steady state CR Complete response CSA Clinical study agreement CSR Clinical study report CT Computed tomography CTCAE Common Terminology Criteria for Adverse Event CTLA-4 Cytotoxic T–lymphocyte-associated antigen 4 Ctrough,ss Trough concentration at steady state CXCL Chemokine (C-X-C motif) ligand DoR Duration of response EC Ethics Committee, synonymous to Institutional Review Board and  Independent Ethics Committee69 | Page   |
|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|  
| Abbreviation     | or                                        | Explanation   |
|------------------|-------------------------------------------|---------------|
| special term ECG | Electrocardiogram                         |               |
| ECOG             | Eastern Cooperative Oncology Group        |               |
| eCRF             | Electronic case report form               |               |
| EDoR             | Expected duration of response             |               |
| EGFR             | Epidermal growth factor receptor          |               |
| EU               | European Union                            |               |
| FAS              | Full analysis set                         |               |
| FDA              | Food and Drug Administration              |               |
| GCP              | Good Clinical Practice                    |               |
| GI               | Gastrointestinal                          |               |
| GMP              | Good Manufacturing Practice               |               |
| hCG              | Human chorionic gonadotropin              |               |
| HIV              | Human immunodeficiency virus              |               |
| HR               | Hazard ratio                              |               |
| IB               | Investigator's Brochure                   |               |
| ICF              | Informed consent form                     |               |
| ICH              | International Conference on Harmonisation |               |
| IDMC             | Independent Data Monitoring Committee     |               |
| IFN              | Interferon                                |               |
| IgE              | Immunoglobulin E                          |               |
| IgG              | Immunoglobulin G                          |               |
| IHC              | Immunohistochemistry                      |               |
| IL               | Interleukin                               |               |
| ILS              | Interstitial lung disease                 |               |
| IM               | Intramuscular                             |               |
| IMT              | Immunomodulatory therapy                  |               |
| IP               | Investigational product                   |               |
| irAE             | Immune-related adverse event              |               |
| IRB              | Institutional Review Board                | 70 | Page     |  
| Abbreviation          | or                                                          | Explanation   |
|-----------------------|-------------------------------------------------------------|---------------|
| special term irRECIST | Immune-related Response Evaluation Criteria in Solid Tumors |               |
| ITT                   | Intent-to-Treat                                             |               |
| IV                    | Intravenous                                                 |               |
| IVRS                  | Interactive Voice Response System                           |               |
| IWRS                  | Interactive Web Response System                             |               |
| mAb                   | Monoclonal antibody                                         |               |
| MDSC                  | Myeloid-derived suppressor cell                             |               |
| MedDRA                | Medical Dictionary for Regulatory Activities                |               |
| MHLW                  | Minister of Health, Labor, and Welfare                      |               |
| miRNA                 | Micro-ribonucleic acid                                      |               |
| MRI                   | Magnetic resonance imaging                                  |               |
| NCI                   | National Cancer Institute                                   |               |
| NE                    | Not evaluable                                               |               |
| NSCLC                 | Non–small-cell lung cancer                                  |               |
| OAE                   | Other significant adverse event                             |               |
| ORR                   | Objective response rate                                     |               |
| OS                    | Overall survival                                            |               |
| PBMC                  | Peripheral blood mononuclear cell                           |               |
| PD                    | Progressive disease                                         |               |
| PDx                   | Pharmacodynamic(s)                                          |               |
| PFS                   | Progression-free survival                                   |               |
| PFS2                  | Time to second progression                                  |               |
| PGx                   | Pharmacogenetic research                                    |               |
| PK                    | Pharmacokinetic(s)                                          |               |
| PR                    | Partial response                                            |               |
| q2w                   | Every 2 weeks                                               |               |
| q3w                   | Every 3 weeks                                               |               |
| q4w                   | Every 4 weeks                                               |               |
| q6w                   | Every 6 weeks                                               | 71 | Page     |  
| Abbreviation     | or                                                              | Explanation   |
|------------------|-----------------------------------------------------------------|---------------|
| special term q8w | Every 8 weeks                                                   |               |
| QTcF             | QT interval corrected for heart rate using Fridericia's formula |               |
| RECIST 1.1       | Response Evaluation Criteria in Solid Tumors, version 1.1       |               |
| RNA              | Ribonucleic acid                                                |               |
| RR               | Response rate                                                   |               |
| RT-QPCR          | Reverse transcription quantitative polymerase chain reaction    |               |
| SAE              | Serious adverse event                                           |               |
| SAP              | Statistical analysis plan                                       |               |
| SAS              | Safety analysis set                                             |               |
| SCLC             | Small cell lung cancer                                          |               |
| SD               | Stable disease                                                  |               |
| SNP              | Single nucleotide polymorphism                                  |               |
| SoC              | Standard of Care                                                |               |
| T3               | Triiodothyronine                                                |               |
| T4               | Thyroxine                                                       |               |
| ULN              | Upper limit of normal                                           |               |
| US               | United States                                                   |               |
| WBDC             | Web-Based Data Capture                                          |               |
| WHO              | World Health Organization                                       |               |