Patients may withdraw from the study at any time and for any reason. A patient may be asked to withdraw from the study by the PI if they are not compliant with the timing of the inoculation series, observation period, or return visits to monitor for study-associated toxicities. Additionally, if the PI determines that it is no longer safe for a patient to continue in the trial for any reason, they may be withdrawn. Because it is not known whether these inoculations might harm an unborn child, patients who are pregnant, plan on becoming pregnant, or who are breast-feeding will not be CONFIDENTIAL Page 36 of 102 Protocol: HERCEPTIN® + E75/GM-CSF Version 3.1 ML25749 05 March 2017 enrolled into the study. Women of childbearing age will take a urine pregnancy test before starting this study and prior to each inoculation; a positive test result will terminate the patient’s participation in the study. Patients will be counseled to avoid becoming pregnant while participating in this study, and that in order to prevent pregnancy they should either have no sexual relations or use a reliable type of birth control. They will be counseled that with the exception of hysterectomy, bilateral oopherectomy, or tubal ligation, birth control methods are not totally effective in preventing pregnancy, and that the only ways to completely avoid the risk of the vaccine or immunoadjuvant alone to an unborn baby are (1) avoid becoming pregnant, or (2) do not receive these inoculations. Patients will be counseled to avoid becoming pregnant for at least 6 months after receiving the inoculations as pregnancy within this time after inoculation administration may be a risk to an unborn baby. If a patient is discontinued from the study for an adverse event or pregnancy, they will continue to be followed for resolution of adverse event and clinical recurrences as described in Section 4.4.2 unless the patient withdraws consent for further study evaluation. The reason for any premature discontinuation of a patient from the study will be recorded on the appropriate Case Report Form (Appendix J). 4.7 STUDY DISCONTINUATION Genentech Study Center, Galena Biopharma, the Data Safety Monitoring Board, Sponsor/Investigator and the Principal Investigator have the right to terminate this study at any time. Reasons for terminating the study may include the following: • The incidence or severity of adverse events in this or other studies indicates a potential health hazard to patients • Subject enrollment is unsatisfactory • Data recording are inaccurate or incomplete • Study protocol not followed 4.8 STATISTICAL METHODS 4.8.1 Analysis of the Conduct of the Study Safety Population The population of patients evaluable for safety will include all patients who receive at least one study inoculation Intention-to-Treat Population The Intention-to-Treat (ITT) population will include all patients who were randomly assigned; ITT analysis will be performed with each randomized patient evaluated in the treatment arm to which randomized (regardless of actual treatment received) CONFIDENTIAL Page 37 of 102 Protocol: HERCEPTIN® + E75/GM-CSF Version 3.1 ML25749 05 March 2017 Per-Protocol Population The Per-Protocol (PP) population is a subset of the ITT population. Patients may be excluded from the PP population for the following reasons and others as determined prior to database lock: • Violations of eligibility criteria • Development of other malignancies • Early recurrences occurring prior to completion of the entire primary vaccine series • Receiving alternative disease-directed therapy without evidence of recurrence • Major deviation from prescribed vaccination scheduled (to include boosters) 4.8.2 Analysis of Treatment Group Comparability Demographic characteristics of all patients in the ITT and PP populations will be tabulated including age, race, country/region, disease histology, tumor size, ER/PR status, grade, HER2 status, nodal status, AJCC staging, surgery extent, and prior disease-directed therapies to include chemotherapy, radiation therapy, hormonal therapy, and immunotherapy. Unless otherwise noted, continuous variables will be summarized using the number of patients, mean, standard deviation, median, minimum, and maximum; and categorical variables will be summarized using the frequency count and the percentage of patients in each category.