Amtagvi Dosage

Pretreatment

Administer a lymphodepleting chemotherapy regimen of cyclophosphamide 60 mg/kg intravenously with mesna daily for 2 days followed by fludarabine 25 mg/m2 intravenously daily for 5 days before infusion of AMTAGVI.

Infuse AMTAGVI as soon as possible after 24 hours have elapsed following the last dose of fludarabine, but no later than 4 days.

Premedication

Pre-medicate the patient with acetaminophen and diphenhydramine or another H1-antihistamine, approximately 30 to 60 minutes prior to AMTAGVI infusion.

Avoid prophylactic use of systemic corticosteroids which may interfere with the activity of AMTAGVI.

Preparation of AMTAGVI

Do not thaw the product until it is ready to be infused. Coordinate the timing of AMTAGVI thaw and infusion. Confirm the infusion time in advance and adjust the start time for thaw so that AMTAGVI is available for infusion when the patient is ready. Once 1 bag of AMTAGVI is thawed, the infusion should be started as soon as possible and must be completed within 3 hours at room or ambient temperature (18°C to 25°C).

1.

Confirm the availability of IL-2 (aldesleukin).

2.

Prior to AMTAGVI preparation, match the recipient's identity with the patient identifiers on the AMTAGVI cassette label. Do not remove the AMTAGVI infusion bag from the cassette if the patient identifiers on the AMTAGVI cassette label do not match the intended patient. Contact Iovance Biotherapeutics, Inc. at 1-833-400-IOVA if there are any discrepancies.

3.

Once recipient identification on the cassette is confirmed, remove the AMTAGVI infusion bag from the cassette. Check that the patient identifiers on the cassette label match the patient identifiers on the AMTAGVI infusion bag label and match the recipient's identity with the patient identifiers on the AMTAGVI infusion bag label. Contact Iovance Biotherapeutics, Inc. at 1-833-400-IOVA if there are any discrepancies.

4.

Inspect each bag for any breaks or cracks prior to thawing. Inspect the spike ports for any damage prior to thawing. If a bag is damaged or compromised, do not infuse the contents and contact Iovance Biotherapeutics, Inc. at 1-833-400-IOVA.

5.

For thawing, place the infusion bag inside a second sealable bag (preferably sterile) per local guidelines in case of a leak and to protect ports from contamination.

6.

Thaw AMTAGVI at approximately 35°C to 39°C using either a water bath or a dry thaw method until there is no visible ice or frozen contents in the infusion bag. Total time from start of thaw until completion of thawing should be no more than 10 minutes.

7.

Immediately remove bag from thawing device. Remove the infusion bag from the sealable plastic bag and wipe dry. Do not wash, spin down, or resuspend AMTAGVI in new media prior to infusion.

8.

Once thawed, administer each bag of AMTAGVI as soon as possible. If needed, AMTAGVI may be maintained at room temperature (18°C to 25°C) not to exceed 3 hours. Do not re-freeze or refrigerate thawed product.

9.

Prior to infusion, inspect the contents of the thawed infusion bag. If cell clumps are visible, gently mix the contents of the bag by inverting the bag prior to infusion. If needed, gently massage the bag to disperse cell clumps. Do not infuse the contents of an infusion bag if it is damaged or leaking, or otherwise appears to be compromised.

Infusion of AMTAGVI

10.

Before infusion, the patient's health status should be reassessed and confirmed to be acceptable prior to AMTAGVI and IL-2 administration.

11.

Confirm the patient's identity matches with the patient identifiers on the infusion bag.

12.

Do NOT use a leukocyte depleting filter with AMTAGVI.

13.

Prime the tubing with normal saline prior to infusion.

14.

Initiate the infusion. Infuse the entire contents of each bag as soon as possible but within 3 hours of thawing.

15.

Administer AMTAGVI at an infusion rate of approximately 1 mL per minute for the initial 5 minutes; thereafter 5 mL to 10 mL per minute.

16.

Contents of all bags must be infused to complete a single dose. After the last bag is infused, rinse the tubing with normal saline at the same infusion rate to ensure all product is delivered.

AMTAGVI contains human cells. Follow universal and local biosafety guidelines applicable for the handling and disposal of AMTAGVI to avoid potential transmission of infectious diseases.