Verwei j. New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1). Eur J Cancer. 2009 Jan;45(2):228 -47. J1790 / Version 7.0/ December 10, 2020 90 APPENDIX D: Immune -Related Response Criteria Comparison between RECIST 1.1 criteria and the irRC RECIST 1.1 irRC RECIST 1.1 New, measurable lesions (i.e., ≥ 5mm) Always represent PD Incorporated into tumor burden New, non- measurable lesions (i.e., < 5mm) Always represent PD Does not define progression (but precludes irCR) Non-index lesions Changes contribute to defining best overall response (BOR) of CR, PR, SD, and PD Contribute to defining irCR (complete disappearance required) CR Disappearance of all lesions in two consecutive observations not less than 4 week apart Disappearance of all lesions in two consecutive observations not less than 4 week apart if single arm trial and primary endpoint only PR > or = 30% decrease in the sum of the diameters of all index lesions compared with baseline in two observations at least 4 week apart, in absence of new lesions or unequivocal progression of non -index lesions ≥ 30% decrease in tumor burden compared with baseline in two observations at least 4 week apart if single arm trial and primary endpoint only SD < 30% decrease in sum of longest diameters of all index lesions compared with baseline cannot be established nor < 20% increase compared with nadir, in the absence of new lesions or unequivocal progression of non -index lesions < 30% decrease in tumor burden compared with baseline cannot be established nor < 20% increase compared with nadir PD At least 20% increase in the sum of the longest diameters of index lesions and/or unequivocal progression of non -index lesions At least 20% increase in tumor burden compared with nadir (at any single time point) in two consecutive observations at least 4 week apart Handling of lymph nodes Lymph nodes are considered pathologically enlarged if > 10 mm in SAD. To be measurable, nodal lesions must be ≥ 15 mm in SAD. Nodal lesions with SAD > 10 mm and < 15 mm are non- measurable. The sum of the diameters (LD for extranodal target lesions, SAD for nodal lesions) is followed through the course of therapy Not differentiated from other tumor measurements J1790 / Version 7.0/ December 10, 2020 91 Derivation of irRC Overall Responses (Modified for RECIST 1.1. Criteria) Measurable response Non-measureable response Overall response Index and new, measurable lesions (tumor burden)* % Non-index lesions New, non- measurable lesions Using irRC ↓ 100 Absent Absent irCR/\ ↓ 100 Stable Any irPR/\ ↓ 100 Unequivocal progression Any irPR/\ ↓ ≥ 30 Absent/ Stable Any irPR/\ ↓ ≥ 30 Unequivocal progression Any irPR/\ ↓ <30 to <20↑ Absent/ Stable Any irSD ↓ <30 to <20↑ Unequivocal progression Any irSD ≥ 20↑ Any Any irPD/\ *Decreases assessed relative to baseline, including measurable lesions only (>5 x 5 mm). /\Assuming response (irCR or irPR) and progression (irPD) are confirmed by a second consecutive assessment at least 4 weeks apart. Defining immune -related Response Criteria by RECIST 1.1 criteria at 20 weeks (irDCR at 20 weeks): 1. Any patient with stable disease or progressive disease at any time in the trial with "rapid clinical deterioration" felt to be related to disease progression is irPD 2. Any patient who meets the criteria for RECIST 1.1 CR at 20 weeks is irCR 3. Any patient who meets the criteria for RECIST 1.1 PR at 20 weeks is irPR 4. Any patient who meets the criteria for RECIST 1.1 SD at 20 weeks is irSD 5. A patient with RECIST 1.1 PD but no rapid clinical deterioration may stay on study if his/her next tumor measurement evaluation is stable disease or better. 6. If patient has first time PD by RECIST 1.1 criteria, call it unconfirmed PD for irRC RECIST 1.1. 7. A patient with unconfirmed irPD at 20 weeks whose next tumor measurement is SD or better will be considered to be included in the irDCR at 6 months. 8. A patient with unconfirmed irPD at 20 weeks who fails to qualify for RECIST 1.1 SD or unconfirmed CR or PR by next tumor measurement will be considered to have RECIST 1.1 PD and irPD at 20 weeks.