21 4. MATERIALS AND METHODS ........................................................................ 22 4.1 Subjects .............................................................................................. 22 4.1.1 Subject Selection .................................................................. 22 4.1.2 Inclusion Criteria ................................................................... 23 4.1.3 Exclusion Criteria ................................................................. 23 4.2 Method of Treatment Assignment ....................................................... 24 4.3 Study Treatment .................................................................................. 24 4.3.1 Herceptin Formulation .......................................................... 25 4.3.2 Herceptin Dosage, Preparation, Administration, and Storage 25 4.3.3 Herceptin Dosage Modification ............................................. 27 4.3.4 Herceptin Overdosage ......................................................... 27 4.3.5 Vaccine ................................................................................. 27 4.3.6 Inoculation Series - Administration ....................................... 29 4.3.7 Booster Inoculations ............................................................. 29 4.4 Study Assessments ............................................................................ 29 4.4.1 Assessments during Treatment ............................................ 30 4.4.2 Follow-Up Assessments ....................................................... 31 4.4.3 Human Biological Specimens ............................................... 31 4.4.4 Specimen Processing ........................................................... 32 4.4.5 HLA-A2/A3/A24/A26 Testing ................................................ 33 4.4.6 Dimer Assay ......................................................................... 33 CONFIDENTIAL Page 3 of 102 Protocol: HERCEPTIN® + E75/GM-CSF Version 3.1 ML25749 05 March 2017 4.4.7 ELISPOT Assay ................................................................... 33 4.4.8 Local Reaction ......................................................................