To facilitate Aduro’s rapid dissemination of information about AEs to other investigators or sites in a multicenter study by using expediting reporting 4. To facilitate investigator reporting of unanticipated problems involving risk to human subjects to the IRB and institutional biosafety committee In the event an SAE is observed, the SAE report will be completed as thoroughly as possible including the following: • All available details about the event • Signature of the in vestigator The SAE report will be forwarded to the sponsor or designee within the designated time frames. If the investigator does not have all information about an SAE, the investigator will not wait to receive additional information before notifying the sponsor of the event and completing the form. The form will be updated when additional information is received. Aduro will report all SAEs that are unexpected and considered possibly or probably related to the administration of the investigational agents to the Food and Drug Administration in the form of an expedited safety report within 15 calendar days after receiving information on the SAE. Aduro will also report to the United States Food and Drug Administration (FDA) and National Institutes of Healt h Office of Biotechnology Activities (NIH OBA) by fax or phone within 7 days of receiving the information, any unexpected life -threatening or fatal SAEs that are considered at least possibly associated with the investigational agents. Aduro, or designee, will also notify all participating investigators of expedited safety reports within 15 calendar days after receiving information. The investigators will notify their reviewing IRB and institutional biosafety committee (IBC) as required by institutional policies. Aduro Biotech , Inc. Protocol ADU -CL-02-v8 CRS -207 with Pemetrexed and Cisplatin Version 8, 08 March 2018 Page 57 6.7 FOLLOW -UP OF AEs AND SAEs After the initial AE or SAE report, the investigator is required to proactively follow each subject and provide further information to the safety department in regards to the subject’s condition. All AE(s) and SAE(s) will be followed until: • Resolution • The condition stabilizes • The event is otherwise explained • The subject is lost to follow -up Once the event is resolved, the appropriate AE or SAE report page will be updated. The investigator will also ensure that the fol low-up includes any supplemental information that may explain the causality of the event(s). New or updated information will be recorded on the originally completed AE or SAE report, with all changes signed and dated by the investigator or designee. The u pdated AE or SAE report will then be signed by the investigator and resubmitted to the safety department. 6.8 ADVERSE EVENTS OF SPECIAL INTEREST 6.8.1 S uspected Infection with CRS -207 or Listeria Suspected infection with CRS -207 and/or Listeria are considered adverse events of special interest (AESI) and should be reported following SAE reporting procedures irrespective of temporal relationship to study drug administration. In the event a subject has a positive Listeria or CRS -207 culture at any time during or after study participation, the event should be reported to the Sponsor within 24 hours of the event. All AESIs must be reported for the duration of the study regardless of causality. In the case of a suspected persistent CRS -207 or Listeria infection that has not been confirmed by culture, collection of blood, urine and stool samples in duplicate is recommended. One set of samples should be cultured locally for Aduro Biotech , Inc. Protocol ADU -CL-02-v8 CRS -207 with Pemetrexed and Cisplatin Version 8, 08 March 2018 Page 58 Listeria per institutional guidelines. Culture of cerebrospinal fluid should be obtained for subjects with suspected central nervous system infection. In such instances, analysis of cerebrospinal fluid should also include cell count, protein, glucose, and Gram stain. If samples are positive for Listeria, the Sponsor must be notified immediately, and the duplicate samples and Listeria isolate must be sent to Sponsor or designee for testing to confirm CRS -207. Instructions on collection, storage and shipping of samples for CRS -207 testing are provided in the Central Laboratory Manual. If Listeria ha s been confirmed at the clinical site or an external laboratory, all efforts should be made to obtain a sample of the bacterial isolate from the original positive culture and submit to the Sponsor for strain confirmation; records on all samples cultured during this period must be obtained and provided to the Sponsor. Refer to the Central Laboratory Manual for sample collection and shipping instructions. If infection with CRS -207 is confirmed or suspected, IV antibiotics ( Section 5.2.2.5) should be initiated as soon as possible and follow -up cultures obtained periodically to confirm absence/clearance of any CRS -207 infection. Aduro Biotech , Inc. Protocol ADU -CL-02-v8 CRS -207 with Pemetrexed and Cisplatin Version 8, 08 March 2018 Page 59 7.0 STUDY OR STUDY SITE TERMINATION AND SUBJECT DISCONTINUATION 7.1 PREMATURE STUDY OR STUDY SITE TERMINATION If Aduro, the investigator, the medical monitor, the study monitor, or appropriate regulatory officials discover conditions arising during the study that indicate that the study should be halted or that the study center should be terminated, this action may be taken after appro priate consultation among Aduro, the investigator, the medical monitor, and the study monitor. Conditions that may warrant termination of the study include, but are not limited to the following: • The discovery of an unexpected, serious, or unacceptable risk to the subjects enrolled in the study • A decision on the part of Aduro to suspend or discontinue testing, evaluation, or development of the product for any reason A study conducted at a single study site in a multicenter study may also warrant termination under the following conditions: • Failure of the investigator to enroll subjects into the study at an acceptable rate • Failure of the investigator to comply with pertinent regulations of appropriate regulatory authorities • Submission of knowingly false information from the research facility to Aduro, the study monitor, or appropriate regulatory authority • Insufficient adherence to protocol requirements Study termination and follow -up will be performed in compliance with the conditions set forth in the International Conference on Harmonisation (ICH) E6, Guideline for Good Clinical Practice, Sections 4.12, 4.13, 5.20, and 5.21. 7.2 SUBJECT DISCONTINUATION Subjects will be encouraged to complete the study; however, they may voluntarily withdraw at any time. The investigator will provide a written explanation describing the reason for discontinuation in a source document, which will be Aduro Biotech , Inc. Protocol ADU -CL-02-v8 CRS -207 with Pemetrexed and Cisplatin Version 8, 08 March 2018 Page 60 transcribed to the appropriate CRF page. Subjects who wish to withdraw from the study will be encouraged to complete the planned administration of antibiotics , complete EOS assessments, post -treatment monitoring for CRS -207, and to complete assessments scheduled during the follow-up visit . Subjects who withdraw consent or discontinue treatment before completing at least 2 cycles of chemotherapy will be considered dropouts and may be replaced at the discretion of the lead investigator , sponsor and medical monitor. A subject may be removed from treatment for the reasons listed in Sections 7.2.1 through 7.2.4. 7.2.1 Adverse Event If a subject suffers an AE that, in the judgment of the investigator, Aduro, or the medical monitor, presents an unacceptable consequence or risk to the subject, the subject may be discontinued from further participation in the study. 7.2.2 Intercurrent Illness A subject may be discontinued from the study if, in the judgment of the investigator, the subject develops an intercurrent illness or complication (including progressive disease) that, in any way, justifies withdrawal from the study. 7.2.3 Noncompliance After consultation between the investigator, the medical monitor, or study monitor, and Aduro when appropriate, a subject may be discontinued from the study for the following administrative reasons: • Failure to receive study medication or trea tment as mandated by the protocol • Failure to comply with protocol requirements • Unauthorized, subject- initiated changes in dosing regimen Aduro Biotech , Inc. Protocol ADU -CL-02-v8 CRS -207 with Pemetrexed and Cisplatin Version 8, 08 March 2018 Page 61 7.2.4 Refusal of CTM Administration If, for any reason, the subject refuses CTM administration during the study, the subject may be discontinued from the study, and the reason(s) for refusal will be documented on the appropriate CRF page. Reasonable efforts should be made to monitor the subject for AEs and to complete follow -up assessments.