fax +49 6151 72 6914
annex 3

| Volume of  0.9% sodium  chloride  solution to be  withdrawn  from infusion  bag  (mL)   | Final  nominal  avelumab  concentration  in the  infusion  solution (mg/mL)   |                                                |     |     |     |        |    |
|-----------------------------------------------------------------------------------------|-------------------------------------------------------------------------------|------------------------------------------------|-----|-----|-----|--------|----|
| Volume of                                                                               |                                                                               |                                                |     |     |     |        |    |
| avelumab drug                                                                           |                                                                               |                                                |     |     |     |        |    |
| product to be added  to the infusion bag  (mL)                                          | Final nominal  volume for  administration  (mL)                               | Number of  DP vials  required for  preparation |     |     |     |        |    |
| Dose  level  (mg/kg)                                                                    | Patient´s  bodyweight  (kg)                                                   | Target dose for  administration  (mg)          |     |     |     |        |    |
| 10                                                                                      | 40                                                                            | 400                                            | 20  | 20  | 250 | 1.6    | 2  |
| 10                                                                                      | 120                                                                           | 1200                                           | 60  | 60  | 250 | 4.8    | 6  |
| 10                                                                                      | 200                                                                           | 2000                                           | 100 | 100 | 250 | 8.0    | 10 |
| 0.1                                                                                     | 40                                                                            | 4                                              | 0.2 | 0.2 | 250 | 0.0016 | 1  |
| * Round to the nearest tenth place for DP volume to be added                            |                                                                               |                                                |     |     |     |        |    |  
| Volume of  0.9% sodium  chloride  solution to be  added to the  empty  infusion bag  (mL)   | Volume of                                                                 |                                       |       |     |     |        |    |
|---------------------------------------------------------------------------------------------|---------------------------------------------------------------------------|---------------------------------------|-------|-----|-----|--------|----|
| avelumab drug                                                                               |                                                                           |                                       |       |     |     |        |    |
| product to be added  to the infusion bag (mL)                                               | Final nominal  avelumab  concentration in  the infusion  solution (mg/mL) |                                       |       |     |     |        |    |
| Final nominal  volume for  administration  (mL)                                             | Number of  DP vials  required for  preparation                            |                                       |       |     |     |        |    |
| Dose  level  (mg/kg)                                                                        | Patient´s  bodyweight  (kg)                                               | Target dose for  administration  (mg) |       |     |     |        |    |
| 10                                                                                          | 40                                                                        | 400                                   | 230   | 20  | 250 | 1.6    | 2  |
| 10                                                                                          | 120                                                                       | 1200                                  | 190   | 60  | 250 | 4.8    | 6  |
| 10                                                                                          | 200                                                                       | 2000                                  | 150   | 100 | 250 | 8.0    | 10 |
| 0.1                                                                                         | 40                                                                        | 4                                     | 249.8 | 0.2 | 250 | 0.0016 | 1  |
| * Round to the nearest tenth place for DP volume to be added                                |                                                                           |                                       |       |     |     |        |    |  
V4/25Sep2018
fax +49 6151 72 6914
annex 4

MSB0010718C (Avelumab) Intravenous Administration - **Investigator Sponsored Study** The appropriate details should be filled in here prior to dose preparation (or documented otherwise in the pharmacy files). Patient Name: ______________ Patient Date of Birth: _______________ Patient Weight: ________ kg Equation 1: Dose (mg) = Subject Weight (kg) x _____ mg/kg = Dose (mg) mg Equation 2: Number of avelumab Vials = Dose (mg) / 200 mg/vial = _________ vial(s) Equation 3: Volume of avelumab (mL) = Dose (mg) / 20 mg/mL = (Round to the nearest tenth place)
mL
Equation 4: Volume of Normal Saline (mL) = 250 mL - (from Equation 3) = (Round to the nearest whole number)
mL
Date of dose preparation: ___________________ (dd-mmm-yyyy)
Time at start of dose preparation: _____________(hh:mm) □ AM □ PM
Expiry Date and Time of Prepared Dose:
Expiry Date: __________________ (dd-mmm-yyyy) Expiry Time: _____________(hh:mm) □ AM □ PM
The expiry time is 24 hours from the time the vials were removed from the refrigerator and allowed to reach room temperature Calculation by (Print Name and initials): ________________________ Date: __________(dd-mmm-yyyy) Verified by (Print Name and initials): ________________________ Date: __________(dd-mmm-yyyy)  
| Instructions for Preparation                                                         | Data                                                          |         |
|--------------------------------------------------------------------------------------|---------------------------------------------------------------|---------|
| Indicated type and volume of bag used for dose preparation                           | □ Empty: _______ mL Bag □ Pre-filled: 0.9% NaCl _______mL Bag |         |
| Volume of Normal Saline - Removed from a pre-filled bag (volume from Equation 3), OR | ___________ mL                                                |         |
| - Added to an empty IV bag (volume from Equation 4                                   | □ Removed                                                     | □ Added |
| Volume of avelumab added to prepared IV bag (from Equation 3)                        | ___________ mL                                                |         |  
| Prepared by (Print Name and initials): ________________________ Date: __________(dd-mmm-yyyy)  Verified by (Print Name and initials): ________________________ Date: __________(dd-mmm-yyyy)   |
|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|  
V4/25Sep2018 Contact the responsible Treating Physician immediately to report any dose preparation and administration deviations.  
Comments on dose preparation (record any deviations from Pharmacy Manual instructions; storage time, conditions, etc.):  
V4/25Sep2018
j. reporting assessment and close
annex 4

REPORTING, ASSESSMENT AND CLOSE OUT OF TEMPERATURE
EXCURSIONS - **Avelumab Investigator Sponsored Study**
Please complete Section 1, print, sign and scan, then send to: AvelumabTemperatureExcursion@thermofisher.com Section 1 **: Report (ALL excursions)**  
| Protocol N°/Trial No ( as applicable/if applicable): Reporting Unit/Site/Depot/CMO: Site (include Site Name/Country as applicable / if applicable): Product (DS/DP/IMP/NIMP): Batch N°:  Presentation: Kit or patient N° (only IMP):  Quantity of product affected:  Excursion occurred during: Apparent Cause: Transport  Temperature deviation during storage/transport Storage (CMO/Warehouse)  Refrigerator, cold room, air-conditioning problems Storage (CMO/Depot)  Power failure Storage (CRO/ Site) Other Description of Excursion :  Documentation Attached  Date :  No, justification………………………. Temperature :  Yes (please list) Duration :  Comments / Emergency Action Taken: Datalogger nr.: Person reporting the temperature excursion event  Name/Function/Site:  Signature :  Date :   |
|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|  
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section 2 - assessment (all

| Assessment Visual Appearance:   | Data Assessment :                              |
|---------------------------------|------------------------------------------------|
| Container contents              | Complies with Transport and Storage Conditions |
| Primary packaging               | Data shows allowable excursion only            |
| Secondary packaging             |                                                |  
Result of Assessment by QP/Authorised/Delegate/QC:
Allowable Temperature Excursion - material can be confirmed for intended use, e.g. clinical use
(Section 3 and 4 are not applicable)
Critical Temperature Excursion - requires Assessment/Investigation and decision by QP
(See Page 2 of 2).  
EMD Serono Trackwise reference:
(for critical deviations only, not relevant for Trial Sites/CROs)
Comments:
QP/Authorised/Delegated/QC:  
Name & Function : Signature : Date  
If assessed as allowable excursion, please send the close out to fax n° :
j. reporting assessment and close
section 3 - investigation (critical

EMD **Serono Trackwise Deviation Reference (not relevant for site/CROs):** Excursion Report Reference :
Documentation Reviewed: Record of storage history: YES NO
Data to support the deviation:  
V4/25Sep2018
section 4 - close out
section 3 - investigation (critical

Final Conclusion:  
| The product involved in the deviation can be used: YES   | NO   | (Tick the relevant box )   |
|----------------------------------------------------------|------|----------------------------|  
Comment:
Qualified Person Close Out:  
Name : Signature: **Date(data):**  
PDL-1 inhibition with Avelumab and concurrent second-generation **ADT in African Americans** with castrate-resistant metastatic prostate cancer.