4.8.5 Planned Analyses There are four formal analyses planned for this trial. The primary analysis of the trial will be conducted 24 months after the last patient is enrolled. The secondary analysis will occur 36 months after the last patient is enrolled. There are two interim analyses planned. The first will be conducted when the 150th patient is randomized to assess for safety. This interim analysis will look at the overall safety and specifically the cardiac safety measures between treatment arms. If any significant safety concern is noted by the DSMB, then trial modifications may be warranted. CONFIDENTIAL Page 41 of 102 Protocol: HERCEPTIN® + E75/GM-CSF Version 3.1 ML25749 05 March 2017 Additionally, the DSMB has the authority to stop the trial early for either safety concerns or efficacy. Due to the long enrollment period, the second interim analysis will be conducted 6 months after the last patient is enrolled and will assess both safety and efficacy. The stopping boundary for the latter analysis has been set with a p value = 0.005 resulting in a final p value = 0.048 for the primary analysis (O’Brien-Fleming). 4.8.6 Missing Data Every reasonable attempt will be made to recover any missing data. If any data remains missing that data point will be excluded from analysis for that patient.