RAVE DATA ENTRY GUIDELINES S1400 & SUB-STUDIES. Protocol Ver. 1/8/18

Transcription

1 RAVE DATA ENTRY GUIDELINES S1400 & SUB-STUDIES Protocol Ver. 1/8/18

2 S1400 Forms Case Report Forms Onstudy: Patient & Disease Description Form 3 Onstudy: Prior Treatment Form 4 Source Documentation: Baseline 5 S1400 Request for Sub-study Reassignment 6 S1400 Request for NEW Sub-study Assignment 7 Notice of Progression 8 Status Update Form 9 Intention not to Register Form 10 Follow-up Form 11 Notice of Death Form 12 S1400A, G, and I Sub-Study Forms Onstudy: Patient & Disease Description Form 13 Onstudy: Prior Treatment 14 Onstudy: Laboratory Values 15 Pre-Treatment Laboratory Values 17 Smoking Status Assessment 18 Source Documentation: Baseline 19 Tumor: Assessment Disease Assessment 20 Tumor: Target Lesions 21 Tumor: Non-Target Disease 22 Follow-up Tumor: Assessment 23 Treatment Form 24 Treatment Dose Modification Due to AE Form 25 Adverse Events: Assessment 26 Adverse Events: Report 27 Immune-Related Adverse Event S1400I 30 Site(s) of Progression or Relapse 31 Off Treatment Notice 32 Advanced NSCLC Follow-up Form 33 Notice of Death Form 34 Doc. Version 05FEB2018 Page 1 of 44

3 Case Report Forms (Cont.) S1400F & S1400K Sub-study Forms Eligibility Criteria 35 Onstudy: Patient and Disease Description 36 Onstudy: Laboratory Values 36 Onstudy: Prior Treatment 38 Treatment Form 39 Adverse Events: Report 41 Immune-Related Adverse Event 43 End of Study 44 Doc. Version 05FEB2018 Page 2 of 44

4 S1400 Screening Forms Onstudy: Patient & Disease Description Form Height, Weight & P/S must be obtained within 28 days prior to study entry. The values closest to the registration date are reported. The date of current staging is the date of the most recent test to assess disease (usually a scan or biopsy). It is not the date of a physical exam unless a measurement of a lesion is done at the visit (e.g. skin lesion assessed). The AJCC clinical stage is the stage at the time of study entry, not at original diagnosis. If patient has metastatic disease, either M1a or M1b are entered. If T and N stage are unknown, enter TX, NX, M1a, for example. If patient has had a cigarette within the past year, they are considered a current smoker. If the patient s tumor tissue was tested for PD-L1 expression, please complete this section utilizing information from the PD-L1 report. The Assay refers to the antibody, not the lab that performed the testing. If you are unsure about how to complete any of these fields, upload a redacted copy of the associated PD-L1 report into the Source Documentation: Baseline folder or the DC s a copy (S1400Question@crab.org) to provide guidance. As there are several different conversion charts available for Karnofsky to Zubrod, it is important that the Zubrod scale be used. If the Karnofsky is used, the Zubrod value must also be documented in the medical record. This form is due within 7 days of registration to S1400. Late submission > 3 months is considered a major data delinquency deficiency for baseline forms. Doc. Version 05FEB2018 Page 3 of 44

5 S1400 Screening Forms Onstudy: Prior Treatment Form If patient registered as: Pre-screening, the answer would be No, and the following treatment questions would be left blank. Screening, enter Yes & answer the next questions. This is the date the form was signed by the pathologist, not the date of the pathology report, or when the specimen was obtained or submitted. The form cannot be signed by the CRA/nurse. The Local Pathology Review Form is due within 7 days of Screening/Pre- Screening Registration. Retain a copy of this form in the patient s research file. For Screening patients: Enter the last date of any treatment received, not necessarily the date of the last platinum (this includes Nivolumab). Enter the date of the first scan or biopsy that confirmed progression, after the most recent course of chemotherapy but BEFORE registration to this step. The patient is considered a screening patient if they have progressed on current systemic therapy for stage IV or recurrent disease at the time of registration. The patient is considered a pre-screening patient if they are currently receiving systemic treatment for stage IV or recurrent disease and have not progressed yet. This form is due within 7 days of registration to S1400. Late submission >3 months is considered a major data delinquency deficiency for baseline forms. Doc. Version 05FEB2018 Page 4 of 44

6 S1400 Screening Forms Source Documentation: Baseline The date of procedure is the date the test was done, not the date the document is uploaded or the date of the report. Within 7 days of registration, upload: The pathology report for the initial diagnosis documenting histological confirmation of squamous cell carcinoma and lung primary The Local Pathology Review Form signed by the pathologist prior to specimen submission. Information Regarding the S1400 Local Pathology Review Form Please ensure you are using the most recent version of the Local Pathology Review Form by checking the version number located on the bottom right-hand side of the form. As of October 2017, the most recent version of the Local Pathology Review Form is Version 1.3. The form version in the Master Form Set will always be the most up-to-date; the Master Form Set can be accessed on the S1400 protocol pages on CTSU.org and SWOG.org. If another specimen is submitted, a second Local Pathology Review Form should be completed. Save a copy of all forms for source documentation of adequate tissue confirmation. Doc. Version 05FEB2018 Page 5 of 44

7 S1400 Screening Forms S1400 Request for Sub-study Reassignment If needed, this form can be added from the Add Event drop down box on the subject tab. This form is submitted after receiving a sub-study assignment if the patient does not fulfill the assigned sub-study-specific eligibility criteria. Doc. Version 05FEB2018 Page 6 of 44

8 S1400 Screening Forms S1400 Request for NEW Sub-study Assignment If needed, this form can be added from the Add Event drop down box on the subject tab. This form is ONLY for patients who have progressed on a sub-study and wish to register to a new sub-study. Doc. Version 05FEB2018 Page 7 of 44

9 S1400 Screening Forms Notice of Progression For pre-screening patients, submit this form within 7 days of progression on current therapy. This form will trigger the sub-study assignment for the patient the next morning (provided 16 days have passed since the S1400 Pre-screening registration). Doc. Version 05FEB2018 Page 8 of 44

10 S1400 Screening Forms Status Update Form Submit this form within 21 days of receiving a sub-study assignment, if the patient has not yet registered to their assigned sub-study. If the Notice of Intention not to Register is submitted, this form is no longer required. Doc. Version 05FEB2018 Page 9 of 44

11 S1400 Screening Forms Notice of Intention Not to Register If needed, this form can be added from the Add Event drop down box on the subject tab. This is the last documented contact with the patient. This is the date documented in the medical record that the physician decided the patient will not go on to a sub-study. If tissue was inadequate, there should be documentation whether or not the patient allowed a second biopsy. If patient was not eligible for the sub-study, there should be documentation that a request for sub-study reassignment was submitted, if applicable. If source documents indicate that patient will receive additional treatment, report it here. Submit this form within 7 days of the decision not to register patient to a sub-study. Although the patient will not go onto a sub-study, follow-up continues per Section 14 of the protocol. Doc. Version 05FEB2018 Page 10 of 44

12 S1400 Screening Forms Follow-up Form If any clinic visits, phone calls, labs, scans, biopsies, etc. were done since the last activity date, this should be Yes. This includes treatment with commercial agent(s) that patient received after going off treatment (e.g. Ipilimumab). This is cranial radiation when there are no signs of metastatic disease to the brain. Submit this form at the following time points: For screening/pre-screening patients: Every three months for the first year, then every six months for the second year and annually thereafter after until sub-study registration, the end of Year 3, or patient s death (whichever comes first). For patients who will not be registered to a sub-study: every six months for two years and at the end of Year 3, or patient s death. Doc. Version 05FEB2018 Page 11 of 44

13 S1400 Screening Forms Notice of Death Form Source documentation must be available to support the cause of death that is reported. The source(s) indicated will be viewed at the time of audit. More than one source can be selected. Submit this form within 28 days of knowledge of death. Doc. Version 05FEB2018 Page 12 of 44

14 S1400 Sub-Study Forms Onstudy: Patient & Disease Description Form Record the values closest to the date prior to sub-study registration. Record the stage at the time of substudy registration. If metastatic disease is present, this is either M1a or M1b. registration. If the patient has treated brain metastasis, and there is no subsequent scan demonstrating resolution of the lesions, answer Yes. The stop date & dose of corticosteroids must be documented in the medical record. If unsure about how to complete this section, org or upload into the Rave Source Documentation: Baseline folder a redacted copy of the PD-L1 report for assistance. Submit this form within 7 days of registration to a sub-study. Doc. Version 05FEB2018 Page 13 of 44

15 1400 Sub-Study Forms Onstudy: Prior Treatment If more than one drug, please list each drug on a separate line. Include all treatment for this cancer (stage I IV). Palliative radiation means for pain or symptom control, not for a disease response (e.g. spine RT for pain control). This is generally radiation for stage I III lung cancer. This is major surgery, not a biopsy or port placement. For S1400G: This is the best response to the patient s prior platinum-based chemotherapy treatment. Per S1400G eligibility, the patient must be platinum-sensitive. This question is only on the S1400G Prior Treatment Form. Submit this form within 7 days of registration to a sub-study. Doc. Version 05FEB2018 Page 14 of 44

16 S1400 Sub-Study Forms Onstudy: Laboratory Values If no 24-hour urine is done, leave the measured creatinine clearance blank. The calculated creatinine clearance value auto populates from the data entered into RAVE. Baseline: record the values obtained closest to the date of registration. Treatment cycles: record the values obtained on or just prior to Day 1 of the next cycle (e.g. For Cycle 1, you would record Cycle 2/Day 1 labs). Submit this form Baseline: Within 7 days of registration Treatment: Within 7 days after each cycle Doc. Version 05FEB2018 Page 15 of 44

17 S1400 Sub-Study Forms Sub-study I: This is Free T3 & T4, not total T3 & T4. For conversion to ng/dl see: vert/pg_mlng_dl.php Submit this form immediately within 7 days after each cycle. Doc. Version 05FEB2018 Page 16 of 44

18 S1400 Sub-Study Forms Pre-Treatment Laboratory Values Enter Yes if additional laboratory values were obtained before Treatment on Cycle 1, Day 1. If Yes, the Pre- Treatment Lab Form will appear. Enter the Cycle 1 Day 1 labs on this form. The Calculated creatinine clearance will auto populate after the Cycle 1 weight is entered on the Cycle 1 Treatment form. An overdue icon may appear until the Cycle 1 Treatment form is submitted, but no further action is required on this form. Doc. Version 05FEB2018 Page 17 of 44

19 S1400 Sub-Study Forms Smoking Status Assessment If patient answers less than one year, they are considered a current smoker. These questions should be answered by the patient at Baseline & at Off-Treatment. A copy of this form can be printed for the patient to complete. There should be documentation of the date and who completed the form (e.g. If patient completes the form, they should sign and date it). The form can be obtained from the Master Forms Set available on the protocol page on both the SWOG and CTSU websites. Scroll through the Master Forms Set to the Smoking Status Assessment Form. If utilizing a progress note to support the data entered on this form, it should be clear that these questions were asked specifically of the patient. This form is due within 7 days of registration to the sub-study & within 7 days of going offtreatment. Doc. Version 05FEB2018 Page 18 of 44

20 S1400 Sub-Study Forms Source Documentation: Baseline This should be the date the scan or procedure was performed, not the date of the report. Click on the browse button to locate the document on your computer to upload. Upload the reports for: CT or MRI brain scan CT of the Chest/Abdomen/Pelvis Any other report used to assess baseline disease PRIOR to sub-study registration These documents should be uploaded in RAVE within 7 days of registration to the sub-study. Doc. Version 05FEB2018 Page 19 of 44

21 Baseline Tumor: Assessment Disease Assessment S1400 Sub-Study Forms If following target lesions enter yes. If following non-target lesions enter yes. If the physician is giving the reported measurements, then physician should be listed here. If a PET scan was done within 42 days prior to registration to the substudy, enter Yes and the date. If CT or MRI brain scan, or other negative test was done, list it here. Submit this form within 7 days of sub-study registration. All scans used to assess disease are to be uploaded into TRIAD within 7 days per Section 15. Doc. Version 05FEB2018 Page 20 of 44

22 S1400 Sub-Study Forms Tumor: Target Lesions This value auto populates. Source documentation must exist to support measurements entered here. The same method of measurement at baseline must be used at each assessment. For lymph nodes, record the smallest (short axis) diameter (must be > 1.5 cm to be a measurable lesion). Nodules are generally not considered lymph nodes. Doc. Version 05FEB2018 Page 21 of 44

23 S1400 Sub-Study Forms Tumor: Non-Target Disease Non-measurable lesions can include: Measurable lesions that were not selected as target lesions. Since only two lesions per organ and five lesions in total can be selected as target lesions, any additional lesions should be followed as non-target disease. Small lesions (longest diameter < 1.0 cm or pathologic lymph nodes with 1.0 cm to <1.5 cm short axis). Note: Lymph nodes that have a short axis < 1.0 cm (10 mm) are considered nonpathological and should not be recorded or followed. Bone lesions, leptomeningeal disease, ascites, pleural/pericardial effusions, lymphangitis cutis/pulmonitis, inflammatory breast disease, and abdominal masses (not followed by CT or MRI). Previously radiated lesions that have not progressed. All baseline sites of disease must be captured somewhere on the Baseline Tumor forms (either as target lesions or non-target disease). Doc. Version 05FEB2018 Page 22 of 44

24 S1400 Sub-Study Forms For S1400I only (added 10/2/17). Follow-up Tumor: Assessment If symptomatic deterioration is yes, there should be documentation in the Medical Record that the patient s performance status has decreased. If patient progressed, answer No to symptomatic deterioration. Enter any new lesion(s) here. Presence of new lesions constitutes progression. If the report states lesion increased in size from prior scan, then it probably is not a new lesion. For sub-study A and sub-study F, patient must have a confirmation scan > 28 days from initial scan showing progression to meet irprogression criteria in section If progression is shown on the subsequent scan, the date of the initial progression scan is reported as the progression date. Source Documentation: Follow up Follow-up Tumor Assessment Form Scan reports must be uploaded to RAVE in addition to submitting the scan(s) within 7 days to TRIAD per Section 15. Doc. Version 05FEB2018 Page 23 of 44

25 S1400 Sub-Study Forms Treatment Form This date should be at the end of the cycle & can be Day 1 of the next cycle (when the toxicities are assessed). These values should be from Day 1 of the cycle before treatment is given. Utilize your institution s formula for BSA. This is the date treatment started for this cycle. ** Be conscious of the dates. There should be no gaps in dates between cycles. ** This should be Day 1 of the next cycle or 30 days after the last treatment was given if removed from study treatment. Sub-study I: Complete the row only for the medication the patient is taking. Leave the others blank. Doc. Version 05FEB2018 Page 24 of 44

26 S1400 Sub-Study Forms Sub-study G: Pharmacokinetic (PK) analysis is required for all patients on S1400G. Please see section 15.3 for additional details regarding specimen collection and submission. Treatment Dose Modification Due to AE Form If treatment was held, reduced or omitted, record the reason on this form. Doc. Version 05FEB2018 Page 25 of 44

27 S1400 Sub-study Forms Adverse Events: Assessment These dates should match the reporting period on the treatment form, except for the last cycle (see help text). All toxicities grade 1 5 are reported even if the event is felt not to be clinically significant. The only exceptions are those present at baseline that have not worsened in grade or reoccurred. Review all toxicities occurring throughout the cycle. If the toxicity assessment is done on Day 1 of the next cycle (before treatment), then those toxicities should be recorded in the prior cycle. For example, if patient is found to have a rash at the toxicity assessment on Day 1 of Cycle 2, this is reported in Cycle 1. Make sure and check all laboratory values. If any laboratory values are out of range, they must be graded per CTCAE 4.0 and reported as an adverse event. If an adverse event occurs in the labs drawn on Day 1 of a cycle, the toxicity is reported for the previous cycle. DO NOT report a condition existing at baseline unless it increases in grade, or returns to normal and then returns. Sub-study A has adverse events of special interest that require expedited reporting in CTEP-AERS. > Grade 1 pneumonitis > Grade 2 AST or ALT if after evaluation it meets Hy s Law Grade 2 bilirubin Any grade Infusion Reactions Any Grade Hypersensitivity Reactions. Sub-study G has adverse events of special interest that require expedited reporting in CTEP-AERS. > Grade 2 AST or ALT > Grade 2 bilirubin Sub-study F also has adverse events of special interest, which are outlined in the S1400F forms section. Doc. Version 05FEB2018 Page 26 of 44

28 S1400 Sub-study Forms Adverse Events: Report DO NOT record a condition existing prior to registration. If a toxicity continues to the next cycle, check AE ongoing, and add that toxicity to the next cycle s adverse event report with the start date from the previous report period. Continue adding the AE for each cycle until it ends. Enter the end date on the cycle where the AE ended. If a baseline toxicity resolves during treatment, then comes back, you will then add that adverse event to the report. Be sure to check all laboratory values done throughout the cycle and not just the ones done on Day1 of the subsequent cycle. Laboratory values that are out of range are reported, even if not clinically significant. Doc. Version 05FEB2018 Page 27 of 44

29 Adverse Events: Report For S1400A MEDI4736 patients only S1400 Sub-study Forms For patients who received MEDI4736 on S1400A, retrospective data collection regarding immunerelated adverse events (iraes) will be required starting with the release of Lung-MAP Revision #9/10 on 10/2/2017. On this form, please indicate if any immune-related AEs were seen during the cycle. If Yes is selected as the response to the question Were any adverse events seen in this reporting period immune-related?, for each adverse event listed in the cycle, please indicate Yes or No to the Is the AE immune-related? field that generates. Doc. Version 05FEB2018 Page 28 of 44

30 S1400 Sub-study Forms Adverse Events: Report S1400I For all patients on S1400I, the Adverse Events: Report form has been updated with the release of Lung-MAP Revision #9/10 on 10/2/2017. Both retrospective and ongoing data collection regarding immune-related adverse events (iraes) will be required. On this form, please indicate if any iraes were seen during the cycle. Please also note the addition of the CTEP-AERS report ticket number field for correlation with expedited SAE reporting, and the updated form instructions. If Yes is selected as the response to the question Were any adverse events seen in this reporting period immune-related?, for each adverse event listed in the cycle, please indicate Yes or No to the Is the AE immune-related? field that generates. If any AE s in this reporting period were immune-related, this question must be answered for all loglines. A separate Immune-Related Adverse Event supplemental form will generate for each adverse event term where this question is answered Yes. If the adverse event warranted expedited reporting via the CTEP-AERS system, please enter the CTEP-AERS report ticket number here. The grade and attribution of the event should match the CTEP-AERS report. Doc. Version 05FEB2018 Page 29 of 44

31 S1400 Sub-study Forms Immune-Related Adverse Event Form S1400I If Yes is selected as the response to the question Is the AE immune-related? for a specific adverse event, a supplemental Immune-Related Adverse Event form will be generated for each immune-related adverse event in the cycle. A separate form will need to be completed for each immune-related adverse event. Use Add a new Log line as needed to list multiple concomitant agents. For concomitant agents administered for the treatment of immune-related AEs, please only list a stop date within the corresponding cycle; if treatment was still ongoing at the end of the cycle, please mark the Ongoing checkbox instead. Doc. Version 05FEB2018 Page 30 of 44

32 S1400 Sub-study Forms Site(s) of Progression or Relapse This date should match the date of the scan demonstrating progression. This is disease status at the primary lung site, on the same side. These are lymph nodes, not nodules. Check all that apply. Any lesion that is new, and not just enlarged, should be reported on the NEW LESIONS section of the Follow-up: Tumor Assessment Form. Doc. Version 05FEB2018 Page 31 of 44

33 S1400 Sub-study Forms Off Treatment Notice If they received even one dose while on protocol, this is Yes. If off treatment for more than one reason (e.g. symptomatic deterioration and progression) record the main reason the patient came off study. Explain in comments. If the patient came off treatment for: Progression: enter the date of the scan that demonstrated progression Positive biopsy that confirmed progression seen on a scan: enter the date of the scan, not the date of the biopsy. Toxicity or Patient Decision: enter the date the decision was made to remove the patient from the protocol. All toxicities continue to be collected until 30 days after the last dose of drug or resolution to baseline. Please note: For patients on S1400I, serious AEs occurring within 100 days after last administration of the protocol agents require expedited reporting. For patients on S1400F, serious AEs occurring within 90 days after last administration of the protocol agents require expedited reporting Doc. Version 05FEB2018 Page 32 of 44

34 S1400 Sub-study Forms Advanced NSCLC Follow-up Form This can be from a clinic visit or a test. If this form is being completed at the time of disease progression, state yes. This includes protocol treatment that is continued after off treatment (e.g. Docetaxel). If the Off Treatment Form indicated a treatment that has started during this report period, report yes. Please refer to section 14 of the sub-study protocol for the follow-up schedule. Doc. Version 05FEB2018 Page 33 of 44

35 S1400 Sub-study Forms Notice of Death Form There must be a source document in the patient s record to support this date. This form is due within 28 days of knowledge of death. Doc. Version 05FEB2018 Page 34 of 44

36 S1400F & S1400K Sub-study Forms Due to new clinical research data reporting requirements, S1400F & S1400K forms have many features that are not found in other sub-study Rave forms. This section covers the these forms and their data entry requirements. Eligibility Criteria This form contains the protocol section 5 eligibility criteria. A response must be provided for each criterion listed; none should be left blank. An example from S1400F is provided in the screenshot below. Doc. Version 05FEB2018 Page 35 of 44

37 Onstudy: Patient and Disease Description S1400F & S1400K Sub-study Forms Onstudy: Laboratory Values - Baseline If any of the data points on this form require clarification with additional comments, the comments must have the corresponding question number selected in the log line. Onstudy: Laboratory Values Baseline LLN, ULN, and Sample collection date are required for each lab value. S1400F: This is Free T3 & T4, not total T3 & T4. Doc. Version 05FEB2018 Page 36 of 44

38 Onstudy: Laboratory Values Baseline LLN, ULN, and Sample collection date are required for each lab value. S1400K: S1400F & S1400K Sub-study Forms Please note these labs specific to S1400K Doc. Version 05FEB2018 Page 37 of 44

39 S1400F & S1400K Sub-study Forms Onstudy: Prior Treatment Baseline S1400F: At least one Anti-PD-1 antibody monotherapy and/or Anti- PD-L1 antibody monotherapy must be selected with additional information provided. See examples of potentially applicable monotherapy agents below. Please specify patient s prior therapies by selecting the appropriate option in the drop-down box and typing in additional details in the adjacent text box as needed. Typing a response in the drop-down box field box will generate a non-conformant data error. Examples of anti-pd-1 antibody monotherapy: Pembrolizumab Nivolumab Examples of anti-pd-l1 antibody monotherapy: Atezolizumab Durvalumab Avelumab Doc. Version 05FEB2018 Page 38 of 44

40 S1400F & S1400K Sub-study Forms Treatment Form S1400F: Patient s vital signs should be monitored before, during, and after the infusion and recorded on the appropriate cycle treatment form. This is required for every cycle. Times should be reported in a 24-hour format. Note these fields asking for supplemental information regarding the infusion. Times should be reported in 24-hour format. Doc. Version 05FEB2018 Page 39 of 44

41 S1400F & S1400K Sub-study Forms Treatment Form S1400K: Record collection times for peripheral blood samples (for PK/ADA/nAB) on Cycles 1-4. Please note these samples should be logged in SWOG Specimen Tracking and shipped to Lab #201. Note these fields asking for supplemental information regarding the infusion. Times should be reported in 24-hour format. Doc. Version 05FEB2018 Page 40 of 44

42 S1400F & S1400K Sub-study Forms Adverse Events: Report Only for S1400F Required for S1400F and S1400K - S1400F: Moving forward, all sub-studies that utilize immunotherapy agents will collect data regarding immune-related adverse events. For each AE listed on the S1400F form, please indicates Yes or No in the Is the AE immune-related? field. For each adverse event where Yes in this field is selected, a new Immune-Related Adverse Event form will generate in the cycle folder. Doc. Version 05FEB2018 Page 41 of 44

43 S1400F & S1400K Sub-study Forms Adverse Events: Report (continued) - Serious adverse events as defined in sub-study protocol section 16 should have Yes indicated in the Serious field. Associated CTEP-AERS report ticket numbers should be added in the corresponding field; please see section 16.0.e for instructions regarding SAE reporting. - For S1400K, the post dosage expedited reporting requirement window is 30 days. - For S1400F, the post dosage expedited reporting requirement window has been extended to 90 days rather than the normal 30 day requirement or until the initiation of alternative anticancer therapy. - Sub-study F has adverse events of special interest, and requires expedited reporting in CTEP- AERS: o Any Grade Diarrhea / Colitis o Any Grade Pneumonitis / ILD o Any Grade ALT/AST increases / hepatitis / hepatotoxicity o Any Grade Neuropathy / neuromuscular toxicity (e.g., Guillain-Barré, and myasthenia gravis) o Any Grade Endocrinopathies (i.e., events of hypophysitis, hypopituitarism adrenal insufficiency, diabetes insipidus, hyper- and hypothyroidism and type I diabetes mellitus) o Any Grade Rash / Dermatitis o Any Grade Nephritis / Blood creatinine increases o Any Grade Pancreatitis (or labs suggestive of pancreatitis - increased serum lipase, increased serum amylase) o Any Grade Other inflammatory responses that are rare with a potential immune-mediated aetiology include, but are not limited to, myocarditis, pericarditis, and uveitis. Doc. Version 05FEB2018 Page 42 of 44

44 S1400F & S1400K Sub-study Forms Immune-Related Adverse Event S1400F: This form generates for every adverse event in the Adverse Events: Report form that is indicated as immune-related. Use Add a new Log line as needed to list multiple concomitant agents. For concomitant agents administered for the treatment of immune-related AEs, please only list a stop date within the corresponding cycle; if treatment was still ongoing at the end of the cycle, please mark the Ongoing checkbox instead. Doc. Version 05FEB2018 Page 43 of 44

45 S1400F & S1400K Sub-study Forms End of Study Form - Please only complete this form if the patient has gone off study, which is defined as: o reaching or expiring prior to maximum protocol-defined follow-up of 3 years, or o being documented as lost to follow-up per SWOG Policy #30, or o patient withdrawal of consent to all protocol treatment and follow-up on the study, per SWOG Policy #30. - If the patient withdraws consent to all study follow-up, even after coming off protocol treatment, please also complete the Lost to Follow-Up form in this patient s Rave chart. - This is not the same as removal from protocol treatment, which should be documented in the Off Treatment Notice. Doc. Version 05FEB2018 Page 44 of 44