Lifileucel

Adverse reactions associated with these deaths included severe infections (sepsis, pneumonia and encephalitis), internal organ hemorrhage (abdominal hemorrhage and intracranial hemorrhage), acute renal failure, acute respiratory failure, cardiac arrythmia, extensive ascites, liver injury, and bone marrow failure. Because clinical trials are conducted under widely varying conditions, treatment-related mortality rates observed in the clinical trials of a drug may not reflect the rates observed in practice. 5.2 Prolonged Severe Cytopenia Patients treated with AMTAGVI may exhibit Grade 3 or higher cytopenia for weeks or longer.

Monitor patients with signs and symptoms of respiratory failure before and after AMTAGVI infusion. Withhold or discontinue AMTAGVI infusion if severe acute respiratory failure is indicated, or patient is deemed ineligible for IL-2 (aldesleukin) infusion. 5.7 Acute Renal Failure Patients treated with AMTAGVI may develop worsened renal function which has been associated with deaths.

Monitor patients with signs and symptoms of acute renal failure before and after AMTAGVI infusion. Withhold or discontinue AMTAGVI if severe acute renal injury is indicated, or patient is deemed ineligible for IL-2 (aldesleukin) infusion. 5.8 Hypersensitivity Reactions Allergic reactions including serious hypersensitivity (e.g., anaphylaxis) may occur with the infusion of AMTAGVI.

Administration AMTAGVI is for autologous use only. The patient's identity must match the patient identifiers on the AMTAGVI cassette(s) and infusion bag(s). Preparing Patient for AMTAGVI Infusion Confirm availability of AMTAGVI and IL-2 (aldesleukin) prior to starting the lymphodepleting regimen. Pretreatment Administer a lymphodepleting chemotherapy regimen of cyclophosphamide 60 mg/kg intravenously with mesna daily for 2 days followed by fludarabine 25 mg/m 2 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.

Receipt of AMTAGVI AMTAGVI is shipped directly to the treatment center in the vapor phase of a liquid nitrogen cryoshipper. All treatment centers should have onsite storage in vapor phase of liquid nitrogen. Product and patient-specific labels are located on both the product infusion bag(s) and protective metal cassette(s), which are inside the liquid nitrogen cryoshipper.

Match the identity of the patient with the patient identifiers on the cassette(s) and infusion bag(s) upon receipt. Confirm the number of AMTAGVI cassette(s) and infusion bag(s) matches the total number of cassettes and infusion bags on the shipment packing slip. Store AMTAGVI frozen in the vapor phase of liquid nitrogen (less than or equal to minus 150°C).

Administration of AMTAGVI The AMTAGVI dose is contained in 1 to 4 cryopreserved patient-specific infusion bag(s) in individual protective metal cassette(s). Thaw and infuse 1 bag at a time if more than 1 bag has been provided. Wait to thaw the next bag until the previous bag has been safely and completely administered. 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).

Confirm the availability of IL-2 (aldesleukin). 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.

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. 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.

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. 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. 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. 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. 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 Before infusion, the patient's health status should be reassessed and confirmed to be acceptable prior to AMTAGVI and IL-2 administration. Confirm the patient's identity matches with the patient identifiers on the infusion bag.

Do NOT use a leukocyte depleting filter with AMTAGVI. Prime the tubing with normal saline prior to infusion. Initiate the infusion. Infuse the entire contents of each bag as soon as possible but within 3 hours of thawing. 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.

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.

Administration of IL-2 (aldesleukin) Beginning 3 to 24 hours after AMTAGVI infusion, administer intravenous IL-2 (aldesleukin) at 600,000 IU/kg every 8 to 12 hours for up to a maximum of 6 doses to support cell expansion in vivo . IL-2 (aldesleukin) should be administered in an inpatient setting under the supervision of a physician experienced in the use of anticancer agents.