Unexpected (in term nature, severity, or frequency) given the following: a) the research procedures described in the protocol-related documents such as the IRB approved research protocol, informed consent document or Investigator Brochure (IB); and b) the characteristics of the subject population being studied; AND 2. R elated or possibly related to participation in the research (possibly related means there is a reasonable possibility that the incident, experience, or outcomes may have been caused by the drugs, devices or procedures involved in the research); AND 3. S uggests that the research places subjects or others at greater risk of harm (including physical, psychological, economic, or social harm) than previously known or recognized. 7.4 Reporting of Unanticipated Problems and Adverse Even ts Page 21 of 50 IRB Protocol No. 12367 Version Date: 10/24/2017 Version: 09 Unan ticipated Problems: Most unanticipated problems must be reported to the COH DSMC a nd IRB within 5 calendar days a ccording to definitions and guidelines at htt p://www.coh.org/hrpp/Pages/hrpp-policies.aspx . Any unanticipated problem that occurs during the study conduct will be reported to the DSMC and IRB by submitting electronically in iRIS (http://iris.coh.org). Serious Adverse Events - All SAEs occurring during this study, whether observed by the ph ysician, nurse, or reported by the patient, will be reported according to definitions and guidelines at http://www.coh.org/hrpp/Pages/hrpp-policies.aspx and Table 2 below. Those SAEs that re quire expedited reporting will be submitted electronically in iRIS ( http://iris.coh.org/ ). Adverse Events - Adverse events will be monitored by the PMT. Adverse events that do not mee t the criteria of serious OR are not unanticipated problems will be reported only in the protoc ol continuation reports and PMT report (see Table 2 below). Page 22 of 50 IRB Protocol No. 12367 Version Date: 10/24/2017 Version: 09 T able 2: City of Hope Adverse Event and Unanticipated Problem Reporting Timelines for the DSMC and IRB Required Reporti ng Timelines to DSMC for AE/SAEs Investigator Initiated Studies Required Reporting Timeframe to DSMC Attribution UNEXPECTED EXPECTED Death while on active treatment or within 30 days of last day of treatment Possibly, Probably, Definitely 5 cale ndar days Unlikely, Unrelated Death after 30 days of last active treatment/therapy Possibly, Probably, Definitely 5 calendar days No reporting required Unlikely, Unrelated No reporting required No reporting required Grades 3 and 4 AND meeting the definition of "serious" Possibly, Probably, Definitely 5 calendar days 10 calendar days Unlikely, Unrelated 5 calendar days 10 calendar days Grades 1 and 2 AND resulting in "hospitalization" Possibly, Probably, Definitely 5 calendar days 10 calendar days Unlikely, Unrelated 10 calendar days 10 calendar days Page 23 of 50 IRB Protocol No. 12367 Version Date: 10/24/2017 Version: 09 Externally Sponsored Studies Required Reporting Timeframe to DSMC Attribution UNEXPECTED1 EXPECTED Death while on active treatment or within 30 days of last day of treatment Possibly, Probably, Definitely No DSMC reporting required - IRB reporting may be necessary Unlikely, Unrelated Death after 30 days of last active treatment/therapy Possibly, Probably, Definitely No DSMC reporting required - IRB reporting may be necessary Unlikely, Unrelated Grades 3 and 4 AND meeting the definition of "serious" Possibly, Probably, Definitely No DSMC reporting required - IRB reporting may be necessary Unlikely, Unrelated Grades 1 and 2 Possibly, Probably, Definitely No DSMC rep orting required - IRB reporting may be necessary An event determined by the IRB of record to be an Unanticipated Problem (UP) will be communicated to the Investigator and COH DSMC through the COH IRB Operations Director. The DSMC will review the case and make a determination as to whether the study will be suspended, terminated, amended, or allowed to continue without amendment. Page 24 of 50 IRB Protocol No. 12367 Version Date: 10/24/2017 Version: 09 Required Reporting Timeframe to IRB of Record Attribution UNEXPECTED EXPECTED Death Possibly, Probably, Definitely 5 calendar days Annual Unlikely, Unrelated Annual Annual Grades 3 and 4 AND meeting the definition of a UP Possibly, Probably, Definitely 5 calendar days Annual Unlikely, Unrelated Annual Annual Grade 1 and 2 AND meeting the definition of a UP Possi bly, Probably, Definitely 5 calendar days Annual Unlikely, Unrelated Annual Annual 7.5 Sponsor-Investigator Adverse Event Reporting All SAEs that occur from t he signing of the study specific consent through the duration of the post- therapy adverse event collection period must be reported to Dendreon within 24 hours of being made aware of the SAE. Notification can be made via phone or telefacsimile using an SAE Report Form to be provided by Dendreon. Dendreon Corporation Attn: Safety Manager Facsimile: (206) 829-1647 Phone: (206) 219-7189 After Hours: (206) 274-6774 Significant new information regarding an ongoing SAE and the resolution must be sent to Dendreon within 3 business days of awareness of the new information to Dendreon on the SAE Report Form. 7.6 Safety Reporting Requirements and Timelines – Participating Institutions Only Page 25 of 50 IRB Protocol No. 12367 Version Date: 10/24/2017 Version: 09 T he guideline is to provide a procedure for accurate and timely reporting of serious adverse events (SAEs) from the participating institution to the FDA, to the Principal Investigator (PI) at City of Hope (COH) as well as to Dendreon. The participating institution, participating institution PI and/or study coordinators are responsible for reporting all serious adverse events immediately (within 24 hours after learning of the event) to their local IRB, the PI at City of Hope, the Data Coordinating Center at COH and to Dendreon. The participating investigator must report each serious adverse event, regardless of attribution, to the Principal Investigator and to Dendreon within 24 hours of learning of the occurrence. In the event that the participating investigator does not become aware of the serious adverse event immediately (e.g., participant sought treatment elsewhere), the participating investigator is to report the event within 24 hours after learning of it and document the time of his or her first awareness of the adverse event. After review of Section 7.3 and Section 7.4 above, please report to City of Hope all serious adverse events meeting criteria by telephone (to Dr. Przemyslaw Twardowski and the COH DCC) AND immediately send via fax a copy of the following forms as noted below. Participating Institution SAE Notification Contact Numbers: Dr. Przemyslaw Twardowski Phone: 626-256-4673, ext. 68218 Fax: 626-301-8233 Data Coordinating Center Phone: 626-256-4673 x63968 Fax: 626-301-8422 Dendreon SAE Form (obtain from COH DCC)  Fax Dendreon SAE Form as specified by Dendreon within 24 hours (refer to Section 7.5) to (206) 829-1647  Fax D endreon SAE Form to City of Hope Data Coordinating Center within 24 hours to (626) 301-8422, along with: 1. Notification of Unanctipated Problem/Adverse Event (Appendix “A”).