1. 2 D ose M o dific ati o n A d. p 5 3- D C T here will n o pr e -pla n n e d d ose m o dificati o ns f or t he vacci ne A d. p 5 3 -D C. H ol di n g o ne i n di vi d ual vacci ne ( A d. p 5 3 -D C) d ose or c o m plete disc o nti n uati o n of vacci ne d oses will be at t he discreti o n of t he treati n g p h ysici a n a n d i n c o or di nati o n wit h t he st u d y pri nci pal i n vesti gat or a n d s p o ns or. Protocol: Version 8.0. September 19, 2018 Page | 26 Temporal of permanent discontinuation of Ipi-Nivo or Nivo due to adverse events, will not preclude continuation and/or completion of vaccine administration as planned per protocol. Ipilimumab -Nivolumab (Ipi-Nivo) or Nivolumab (Nivo) Adverse events (both non- serious and serious) associated with Ipi-Nivo or Nivo exposure may represent an immunologic etiology. These adverse events may occur shortly after the first dose or several months after the last dose of treatment. Ipi-Nivo or Nivo must be withheld for drug -related toxicities and severe or lif e-threatening AEs as per Table 3 below. See Section 11.6 Management Algorithms for supportive care guidelines, including use of corticosteroids. NOTE: In cases of an unexpected or unforeseen discrepancy between the guidelines or instructions in Table 3 (below) and Section 11.6 Management Algor ithms, the latter guidelines/instructions should prevail for the purposes of patient management on protocol. Table 3 Dose Modification Guidelines for Drug- Related Adverse Events Toxicity Hold Treatment For Grade Timing for Restarting T reatment Discontinue Subject Diarrhea/Colitis 2 Toxicity resolves to Grade 0 -1. Toxicity does not resolve within 12 weeks of last dose or inability to reduce corticosteroid to 10 mg or less of prednisone or equivalent per day within 12 weeks. 3-4 Permanently discontinue Permanently discontinue AST, ALT, or Increased Bilirubin 2 Toxicity resolves to Grade 0 -1 Toxicity does not resolve within 12 weeks of last dose. 3-4 Permanently discontinue (see exception below)1 Permanently discontinue Type 1 diabetes mellitus (if new onset) or Hyperglycemia T1DM or Hold IPI-NIVO OR NIVO for new onset Type 1 diabetes mellitus or Grade 3 -4 hyperglycemia associated with evidence of beta cell failure. Resume IPI-NIVO OR NIVO when patients are clinically and metabolical ly stable. 3-4 Permanently discontinue Permanently discontinue Hypophysitis 2 Toxicity resolves to Grade 0 -1 Toxicity does not resolve within 12 weeks of last dose or inability to reduce corticosteroid to 10 mg or less of prednisone or equivalent per day within 12 weeks. 3-4 Permanently discontinue Permanently discontinue Hyperthyroidism 2 Toxicity resolves to Grade 0 -1 Toxicity does not resolve within 12 weeks of last dose or inability to reduce corticosteroid to 10 mg or less of prednisone or equivalent per day within 12 weeks. 3-4 Permanently discontinue Permanently discontinue Hypothyroidism 2 Therapy with IPI-NIVO OR NIVO can be continued while treatment for the thyroid disorder is instituted Therapy with IPI-NIVO OR NIVO can be continued while treatment for the thyroid disorder is instituted. 3-4 Permanently discontinue Permanently discontinue Infusion Reaction 3-4 Permanently discontinue Permanently discontinue Pneumonitis 2 Toxicity resolves to Grade 0 -1 Toxicity does not resolve within 12 weeks of last dose or inability to reduce corticosteroid to 10 mg or less of prednisone or equivalent per day within 12 weeks. 3-4 Permanently discontinue Permanently discontinue Protocol: Version 8.0. September 19, 2018 Page | 27 Toxicity Hold Treatment For Grade Timing for Restarting T reatment Discontinue Subject Renal Failure or Nephritis 2 Toxicity resolves to Grade 0 -1 Toxicity does not resolve within 12 weeks of last dose or inability to reduce corticosteroid to 10 mg or less of prednisone or equivalent per day within 12 weeks. 3-4 Permanently discontinue Permanently discontinue All Other Drug- Related Toxicity2 Any Severe Toxicity resolves to Grade 0 -1 Toxicity does not resolve within 12 weeks of last dose or inability to reduce corticosteroid to 10 mg or less of prednisone or equivalent per day within 12 weeks. 3-4 Permanently discontinue Permanently discontinue Note: Permanently discontinue for any severe or Grade 3 drug -related AE that recurs or any life -threatening event. 1 For patients with liver metastasis who begin treatment with Grade 2 AST or ALT, if AST or ALT increases by greater than or equal to 50% relative to baseline and lasts for at least 1 week then patients should be discontinued. 2 Patients with intolerable or persistent Grade 2 drug -related AE may hold study medication at physician discretion. Permane ntly discontinue study drug for persistent Grade 2 adverse reactions for which treatment with study drug has been held, that do not recover to Grade 0 -1 within 12 weeks of the last dose. Dosing interruptions are permitted in the case of medical / surgical events or logistical reasons not related to study therapy (e.g., elective surgery, unrelated medical events, patient vacation, and/or holidays). Subjects should be placed back on study therapy within 3 weeks of the scheduled interruption, unless otherwise discussed with the Sponsor. The reason for interruption should be documented in the patient's study record. 5.2.2 Timing of Dose Administration Trial antibody (checkpoint inhibitor treatment should be administered after all procedures/assessments have been completed as detailed on the Trial Flow Chart (Section 6.0). Trial treatment may be administered up to 7 days before or after the scheduled day due to any medical or administrative/logistical reasons. All trial treatments will be administered on an outpatient basis. Induction Immunotherapy: • Ipilimumab, 3 mg/kg IV q3w x4 cycles • Nivolumab, 1 mg/kg IV q3w x4 cycles. Maintenance Immunotherapy : • Nivolumab, 480 mg (flat dose) IV q4weeks until PD . Sites should make every effort to target infusion timing to be as close as possible (60 min for nivolumab and 90 min for ipilimumab). However, given the variability of infusion pumps from site to site, a window of -10 minutes and +15 minutes is permitted (i.e., infusion time is 60 or 90 minutes: -10 min/+1 5 min , respectively ). The Pharmacy Manual contains specific instructions for the preparation of the Ipi-Nivo or Nivo infusion fluid and administration of infusion solution. Ad.p53- DC (2-5x10 6 DC depending on manufacture cell number yield) will be adminis tered as an intradermal injection as per the trial schema, every 2 weeks x 3 after the first leukopheresis (induction immunotherapy) and in cases of persistant SD upon restaging, again every 4 weeks x 3 after the second leukopheresis (maintenance immunothe rapy). Protocol: Version 8.0.