Overall irPR ≥ 30% decrease in SLD compared with baseline confirmed by a consecutive assessment at least 4 weeks after first documentation . 62 Abbreviated Title: Phase I MVA -Brachyury -TRICOM Version Date: September 14, 2016 Confidential Overall irSD Not meeting criteria for irCR or irPR, in absence of irPD: 30% decrease in SLD compared with baseline cannot be established nor 20% increase compared with nadir. Overall irPD At least 20% increase in SLD compared with nadir (minimum recorded tumor burden) and an increase of at least 5 mm over nadir, confirmed by repeat, consecutive observations at least 4 weeks from t he date first documented. Overall responses derived from changes in index, non-index and new lesions as demonstrated in the following table: Measurable response Non-measurable response Overall response using irRC Index and new, measurable lesions (tumor burden)* % Non-index lesions New, non- measurable lesions Decrease 100 Absent Absent irCR& Decrease 100 Stable Any irPR& Decrease 100 Unequivocal progression Any irPR& Decrease ≥ 30 Absent/ stable Any irPR& Decrease ≥ 30 Unequivocal progression Any irPR& Decrease < 30 to increase < 20 Absent/ stable Any irSD Decrease < 30 to increase < 20 Unequivocal progression Any irSD Increase ≥ 20 Any Any irPD * Decreases assessed relative to baseline & Assuming response (irCR) and progression (irPD) are confirm ed by a second, consecutive assessment at least 4 weeks apart. 63 Abbreviated Title: Phase I MVA -Brachyury -TRICOM Version Date: September 14, 2016 Confidential 13.3 APPENDIX C: RECIST 1.1 CRITERIA The best overall response is the best response recorded from the start of treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since treatment started). The patient's best response assignment will depend on the achievement of both measurement and confirmation criteria. Target lesions Non-target lesions New lesions Overall response Best overall response when confirmation is required* CR CR No CR > 4 weeks confirmation** CR Non-CR/non-PD No PR > 4 weeks confirmation** CR Not evaluated No PR PR Non-CR/non- PD/not evaluated No PR SD Non-CR/non- PD/not evaluated No SD Documented at least once 4 weeks from baseline** PD Any Yes or no PD No prior SD, PR, or CR Any PD*** Yes or no PD Any Any Yes PD See RECIST 1 .1 manuscript for further details on what is evidence of a new lesion. ** Only for non-randomized trials with response as prim ary endpoint. *** In exceptional circumstances, unequivocal progression in non- target lesions may be accepted as disease progression. a. Patients with a global deterioration of health status requiring discontinuation of treatment without objective evidence of disease progression at that time should be reported as “symptomatic deterioration.” Every effort should be made to document the objective progression even after discontinuation of treatment. 64 Abbreviated Title: Phase I MVA -Brachyury -TRICOM Version Date: September 14, 2016 Confidential b. In some circumstances, it may be difficult to distinguish resid ual disease from normal tissue. When the evaluation of complete response depends on this determination, it is recommended that the residual lesions be investigated (fine needle aspirate/biopsy) before confirming complete response status. 13.3.1 Confirmation To be assigned a status of PR or CR, changes in tumor measurements must be confirmed by repeat assessments that should be performed at least 4 weeks after the criteria for response are first met. 13.3.2 Duration of Overall Response The duration of overall response is measured from the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started). The duration of overall CR is measured from the time measurement criteria are first met for CR until the first date that progressive disease is objectively documented. 13.3.3 Measurable Disease Measurable lesions are defined as those that can be accurately measured in at least one dimension (longest diameter to be recorded) as > 20 mm by chest x- ray, as > 10 mm by CT scan, or > 10 mm with calipers by clinical exam. All tumor measurements must be recorded in millimeters (or decimal fractions of centimeters). Note: Tumor lesions that are situated in a previously irradiated area might or might not be considered measurable. 13.3.4 Malignant Lymph Nodes To be considered pathologically enlarged and measurable, a lymph node must be > 15 mm in short axis when assessed by CT scan (CT scan slice thickness recommended to be no greater than 5 mm). At baseline and follow-up, only the short axis will be measured and followed. 13.3.5 Non-Measurable Disease All other lesions (or sites of disease), including small lesions (longest diameter < 10 mm or pathological lymph nodes with ≥ 10 to < 15 mm short axis) are considered non- measurable disease. Bone lesions, leptomeningeal disease, ascites, pleural/pericardial effusions, lymphangitis cutis/pulmonitis, inflammatory breast disease, and abdominal masses (not followed by CT or MRI), are considered non -measurable. Note: Cystic lesions that meet the criteria for radiographically defined simple cysts should not be considered as malignant lesions (neither measurable nor non- measurable) since they are, by definition, simple cysts. 65 Abbreviated Title: Phase I MVA -Brachyury -TRICOM Version Date: September 14, 2016 Confidential Cystic lesions thought to represent cystic metastases can be considered as measurable lesions if they meet the definition of measurability described above. However, if non- cystic lesions are present in the same patient, these are preferred for selection as target lesions. 13.3.6 Evaluable Disease Disease that cannot be measured directly by the size of the tumor but can be evaluated by other methods. 13.3.7 Target Lesions All measurable lesions up to a maximum of 2 lesions per organ and 5 lesions in total, representative of all involved organs, should be identified as target lesions and recorded and measured at baseline. Target lesions should be selected on the basis of their size (lesions with the longest diameter), be representative of all involved organs, but in addition should be those that lend themselves to reproducible repeated measurements. It may be the case that, on occasion, the largest lesion does not lend itself to reproducible measurement in which circumstance the next largest lesion which can be measured reproducibly should be selected. A sum of the diameters (longest for non-nodal lesions, short axis for nodal lesions) for all target lesions will be calculated and reported as the baseline sum diameters. If lymph nodes are to be included in the sum, then only the short axis is added into the sum. The baseline sum diameters will be used as reference to further characterize any objective tumor regression in the measurable dimension of the disease. 13.3.8 Non-Target Lesions All other lesions (or sites of disease) including any measurable lesions over and above the 5 target lesions should be identified as non-target lesions and should also be recorded at baseline. Measurements of these lesions are not required, but the presence, absence, or in rare cases unequivocal progression of each should be noted throughout follow-up. 66 Abbreviated Title: Phase I MVA -Brachyury -TRICOM Version Date: September 14, 2016 Confidential 13.4 APPENDIX D: MODIFIED CHOI CRITERIA The Choi Criteria were introduced for radiographic evaluation of gastrointestinal stromal tumors treated with imatinib mesylate48,49 and have been evaluated in other soft tissue sarcomas50 and renal cell carcinoma.51 After discussion with experts in the field of c hordoma as well as the Chordoma Foundation, we have agreed that, at this point, there is a consensus to use a modified Choi Criteria, with MRI instead of CT, as the best imaging technique to determine radiographic response, stability, or progression in patients with chordoma. The differences between RECIST and Choi Criteria are defined below: