12 7.1.2 Mechanism of Action ............................................................................................... 13 7.1.3 Pharmacodynamics/Kinetics ..................................................................................... 13 7.1.4 Formulation .............................................................................................................. 13 7.1.5 Availability ............................................................................................................... 13 7.1.6 Preparation ................................................................................................................ 13 7.1.7 Packaging and Labeling ............................................................................................ 13 7.1.8 Administration .......................................................................................................... 13 7.1.9 Potential Toxicities ................................................................................................... 14 7.1.10 Return or Destruction of Study Drug ........................................................................ 14 7.2 Cyclophosphamide ............................................................................................................... 14 7.2.1 Agen t Description ..................................................................................................... 14 7.2.2 Receipt and Storage .................................................................................................. 14 7.2.3 Premedication ........................................................................................................... 14 7.2.4 Administration .......................................................................................................... 14 7.2.5 Potential Toxicities ................................................................................................... 15 8.0 STUDY PROCEDURES ............................................................................................................. 15 8.1 Dendritic Cell (mDC3/8) Preparation .................................................................................. 15 DC Vaccine for Colorectal Cancer Page 4 of 34 Version 7.11-11-2021 CONFIDENTIAL This protocol is the property of the University of Pennsylvania. Do not disclose or use except as authorized in writing by the study spons or. 8.2 Treg Depletion ..................................................................................................................... 15 8.3 Administration of Dendritic Cell Vaccines (mDC3/8 vaccines with and without influenza) ............................................................................................................................. 15 8.4 Immune Monitoring ............................................................................................................. 16 8.4.1 Flow Cytometry / p -HLA multimer Staining ........................................................... 16 8.4.2 Cytotoxicity Assays .................................................................................................. 16 8.4.3 TCR Sequencing ....................................................................................................... 17 8.5 Post-DC Vaccine Surveillance ............................................................................................. 17 9.0 POTENTIAL TOXICITY AND DOSE MODIFICATIONS ................................................... 17 9.1 Dose Limiting Toxicity (DLT) ............................................................................................. 17 10.0 STUDY CALENDAR .................................................................................................................. 19 11.0 EARLY WITHDRAWAL OF SUBJECTS ............................................................................... 22 12.0 SAFETY AND ADVERSE EVENTS ......................................................................................... 23 12.1 Definitions ............................................................................................................................ 23 12.2 Recording of Adverse Events ............................................................................................... 25 12.3 Reporting of Serious Adverse Events .................................................................................. 26 12.3.1 Investigator Reporting: Local Regulatory Review Committees ............................... 27 12.4 Pregnancies .......................................................................................................................... 27 12.5 Protocol Exceptions/Deviations ........................................................................................... 27 12.6 Medical Monitorin g ............................................................................................................. 28 12.7 Study Stopping Rules ........................................................................................................... 28 13.0 STATISTICAL CONSIDERATIONS ....................................................................................... 28 14.0 DATA HANDLING AND RECORDKEEPING ....................................................................... 30 14.1 Confidentiality ..................................................................................................................... 30 14.2 Source Documents ............................................................................................................... 30 14.3 Case Report Forms ............................................................................................................... 30 14.4 Records Retention ................................................................................................................ 30 15.0 STUDY M ONITORING, AUDITING, AND INSPECTING ................................................... 31 15.1 Study Monitoring Plan ......................................................................................................... 31 15.2 Auditing and Inspecting ....................................................................................................... 31 16.0 ETHICAL CONSIDERATIONS ................................................................................................ 31 17.0 STUDY FINANCES ..................................................................................................................... 32 17.1 Funding Source .................................................................................................................... 32 17.2 Conflict of Interest ............................................................................................................... 32 17.3 Subject Stipends or Payments .............................................................................................. 32 18.0 PUBLICATION PLAN ...............................................................................................................