7. DOSAGE AND ADMINISTRATION Drug Information: = Preservative-free, sterile, white to greyish-white lyophilisate © Supplied in 20-ce single-use glass vials with 20 mm stoppers. ‘© Vials are filled to enable delivery of 140 mg [7.0 mL] of Pola efter reconstitution with 7.2 mL sterile water for injection (SWF) ‘* Upon reconstitution with 7.2 mL of SWFI, the concentration of Pola is 20 mg/mL in a solution containing sodium succinate, sucrose, and polysorbate-20 at pl! 5.5. ‘+ Density of study drug following reconstitution is 1,02 g/mL. Vial storage conditions and precautions Store at 2°- 8°C (26°F-46°F). Do not freeze. Do not shake. Protect from light. For single use only. Do not use beyond expiration date. ment Required for Infusion * Dose solutions should be prepared in a 100 mL IV infusion bag containing normal saline (0.3% NaCl) and constructed with product contacting materials of polyvinyl chloride (PVC), polyolefin (PO), polyethylene (PE), and/or polypropylene (PP) ‘¢ Do not use infusion bags containing other diluents (e.g. 5% dextrose, Ringers’s solution, etc.) + Use a PVC, PO, PE, or PP [or PUR] infusion line equipped with a 0.2 or 0.22um polyethersulfone (PES) fier. ‘+ Perform manipulations of Pola with standard disposable syringes and stainless stee! needles. Use an appropriate infusion pump capable of delivering the intended dose solution over the intended time range of 30 to 90 (#10) minutes. Reconstitution Instructions. © Reconstitution of the drug product must occur under appropriate aseptic conditions in accordance with local regulations and institutional policy, as Pola contains no preservatives. = Reconstitute the drug product by adding 7.2 mL of sterile water for injection using a 10- mL disposable syringe capable of measuring volume in 0.2 mL increments and a standard stainless steel needle. - The needle should be inserted perpendicular to the surface of the stopper septum, and the syringe should be slowly emptied at the wall to avoid foaming. - Gently swirl vial contents until reconstitution is complete. = The reconstituted drug product should be inspected visually for particulate matter and discoloration Determination of Patient’s weight ‘= The total dose of Pola for each patient will depend on the patient’s body weight at the time of enrollment. For changes > 10% in body weight from time of enrollment for all subsequent doses, the dose should be re-calculated at each subsequent cycle. Dose solution preparation ‘+ Dose solution preparation must occur under appropriate aseptic conditions in accordance with local regulations and institutional policy, as the Pola contains no preservatives. ‘* Calculate the appropriate volume of undiluted drug to the infusion bag using the equations below AG40661_Polatuzumab vedotin Treatment Guidance_V.1— 27 June 2018 Page 6 of 23 F. Hoffmann-La Roche, Ltd. Proprietary and ConfidentialRequired dose (mg) = Patient weight (kg) x 1.8ma/kg Required volume (mL) = Required dose (mg)/20mg/mi_ ‘As an example, a 72 kg patient in the 1.8 mg/kg dose would require a dose of 130 mg. The required volume of reconstituted drug product would be 6 mL in this example, Noie: Every effort o adhere to the calculated doses/volume should be made and unnecessary rounding should be avoided. ‘¢ Prior to the addition of the reconstituted drug product to the IV bag, remove a volume of saline equivalent to the patient-specific volume of reconstituted drug product using an appropriately sized syringe. ‘* Using a new syringe and needle, withdraw the required volume of the reconstituted drug product from the vial, slowly add the required volume of drug product to the IV bag, and gently mix the IV bag by slowly rotating the bag. Inspect the bag for particulates and discard it present. Dose solution handling and storage © Donot shake or freeze infusion bags containing dose solution. Protect from direct sunlight. The reconstituted Pola drug product and the dose solution should be used immediately to limit product degradation and microbial growth in case of potential accidental contamivation, If not used immediately, the reconstituted drug solution may be stored refrigerated at 2-8°C for up to 24 hours prior to dose solution preparation. Within this 24 hour storage period, the reconstituted Pola solution may be temporarily held at 9-25°C up to a maximum of 4 Fours. The reconstituted Pola should be discarded if the cumulative storage time prior to the preparation of the dose solution exceeds 24 hours, ‘¢ Similarly, the dose solution may also be stored refrigerated at 2-8°C for up to 24 hours pror to administration. Within this 24 hour storage period, the dose solution may be temporarily held at 9-25°C up to a maximum of 4 hours. The dose solution should be discarded ifthe Cumulative storage time prior to administration exceeds 24 hours. ‘¢ Transportation of the infusion bags should be avoided to minimize the risk of aggreg formation because Pola dosing solution is sensitive to the air-Iquid interface. If transportation is required, remove ait from the infusion bag and transport the bag only at 2- 8°C. To ensure accurate dosing, an infusion set with a vented spike is required when air has been removed from the infusion bag. Additional instructions and information * No incompatibilties have been observed between Pola and polyvinyl chloride (PVC), polyolefin (PO), polyethylene (PE) and/or polypropylene (PP), acrylonitrile butadiene styrene (ABS), polycarbonate (PC), polyethersulfone (PES), polyetherurethane (PEU), polytetrafluoroethylene (PTFE), and silicone]. The use of administration items constructed of other product-contacting materials is not recommended. Compatibility between Pota end closed system transfer devices (CSTDs) or needle free transfer devices has not been assessed. If CSTDs or needle free transfer devices must be used to comply with site regulations, the site should be aware that thelr use may lead to the introduction of patticles and may not allow the withdrawal of the labeled quantity of drug from the vial. Sites shoukt perform a thorough visual inspection of the IV bag for particulates. In addition, sites must use 0.2 of 0.22 um polyethersulfone (PES) fiter during infusion. The preparation should be discarded if particulates are observed in the IV bag ¢ Adedicated infusion line and catheter should be used for the administration of Pola. The compatibility of Pola with other drugs as well as in-dwelling catheters such as peripherally inserted central catheters (PICs) or other central venous access devices (CVADs) has not been established. If the treating physician determines that the use of a dedicated infusion AG40661_Polatuzumab vedotin_Treatment Guidance_V.1— 27 June 2018 Page 7 of 23, F. Hoffmann-La Roche, Ltd. Proprietary and Confidentie!line and catheter is not feasible, infusion lines and catheters must be flushed before and after administration of Pola to ensure it does not contact other drug solutions. Note: Roche will not provide syringes and needles, and treating physicians has to ensure that adequate material as described above are being made available to the patient (see Instructions for Use TEC-0114455) Premedications for Pola and Rituximab Time point | Patients Who Require | Premedication ‘Administration Premedi Gye t, ‘Al patients Corticosteroid Complete = 1 hour prior to Day 1 MabThera® / Rituxan® infusion ‘Anthistamine drug___| Administer > 30 minutes prior to ‘Analgecic/ant pyrete | MabThera® / Rituxan® infusion; may be administered to patients prior to administration of any Pola as well Cycles Dard | Patients with no RR Corticestercid ‘Complete = 7 hour prior to beyond, during the previous MabThera® / Rituxan® and Pole Day 1 infusion infusion ‘Anthistamine dwg “Administer = 30 minutes prior ‘Analgecic/an pyretic: | infusion. These may be omitted at the investigator's discretion Patients with Grade 1 or2_| Corticosteroid ‘Complete > ‘hour prior IRR during the previous MabThera® / Rituxan® and Pole infusion infusion ‘Anthistamine dng “Administer = 60 minutes prior fo ‘Analgesio/ant pyretic | infusion. These may be omitted at the investigator's discretion Patients with Grade SRR, | Comicosteroid ‘Complete > T hour prior ‘wheezing, urticaria, or MabThera® / Rituxan® and Pole other symptoms of infusion anaphylaxis during the ” ‘Anthistamine dwg “Administer = 30 minutes prior to Previous infusion ‘Analgecic/ans pyretic | infusion. These may be omitted at the Patients with bulky disease investigator's discretion Mabthera® (not / Rituxan® Affiliates will use MabThera®/Rituxan® IV from their local commercial stock, as needed, and will be administered as per label instructions. Polatuzumab vedotin destruction Unused Pola will be disposed offdestroyed at the site according to Good Clinical Practice or returned to the affilate’s depot if the site does not have site-specific drug destruction SOP or procedure. Documentation of destruction is to be provided to the PDMA Pola team. AG40661_Polatuzumab vedotin_Treatment Guidance_V.1- 27 June 2018 Page 8 of 23 F. Hoffmann-La Roche, Ltd. Proprietary and Confidential