0 Dead. 61 Abbreviated Title: Phase I MVA -Brachyury -TRICOM Version Date: September 14, 2016 Confidential 13.2 APPENDIX B: IMMUNE -RELATED RESPONSE CRITERIA Responses will be evaluated in all cohorts to determine eligibility for subsequent cycles, but only responses evaluated in the expanded cohort and in patients enrolled at the MTD will be used for statistical analysis. For the purposes of this study, patients will be re- evaluated for response after day 85 (after 3 doses of vaccine) . Because of direct clinical observations of immune- cell influx into tumor causing tumor enlargement in some patients prior to sustained response, it has recently been suggested that clinical trials involving the use of immunotherapy use alternative guidelines, called immune - related response criteria (irRC) , to determine rad iographic response or progression after therapy . 47 These recommendations have been used in recent clinical trials. One study of 227 subjects with metastatic melan oma showed that the approximately 10% of patients who had PD by modified WHO criteria but either CR, PR , or SD by irRC had overall survival similar to patients who had SD, PR, or CR by both criteria. The irRC were created using bidimensional measurements (as previously widely used in the WHO criteria). We have taken the concepts of the irRC and combined them with the recently revised RECIST 1.1 45 to come up with the modified irRC used in this protocol. Consistent with the irRC, the main changes from RECIST 1.1 are (a) a requirement for confirmation of both progression and response by imaging at least 4 weeks after initial imaging and (b) not automatically calling the appearance of new lesions progressive disease if the total measurable tumor burden has not met criteria for progressive disease. For irRC, only index and measurable new lesions are taken into account. At baseline tumor assessment on this trial, target lesions will be measured along the longest axis and the measurements will be summed, called sum of largest diameter (SLD). These lesions must be a minimum of 10 mm per lesion, maximum of 5 target lesions, maximum of 2 per organ system. At each subsequent tumor assessment, the unidimensional measurement of target lesions and of new measureable lesions is added together to provide the total tumor burden. As per the modified definitions below, all responses and progression except SD require confirmation on a consecutive scan at least 4 weeks from initial observation. Definitions of irRC: Response irRC New measurable lesions Incorporated into tumor burden New non- measurable lesions Do not define progression (but preclude irCR) Non-index lesions Contribut e to defining irCR (complete disappearance required) Overall irCR 100% disappearance of all lesions, whether measurable or not, and no new lesions, in 2 consecutive observations not less than 4 w eeks from the date first documented. Also, a ll mea surable lymph nodes must have reduction in short axis to < 10 mm.