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Lifileucel

FDA Drug Information • Also known as: Amtagvi

Brand Names
Amtagvi
Route
INTRAVENOUS
Dosage Form
SUSPENSION
Product Type
CELLULAR THERAPY

⚠ Boxed Warning (Black Box)

WARNING: TREATMENT-RELATED MORTALITY, PROLONGED SEVERE CYTOPENIA, SEVERE INFECTION, CARDIOPULMONARY and RENAL IMPAIRMENT Monitor patients for prolonged severe cytopenia and monitor for internal organ hemorrhage [see Warnings and Precautions (5.1 , 5.2 , 5.3) ]. Administer filgrastim or a biosimilar product to patients beginning Day 1 after AMTAGVI and continuing daily until the absolute neutrophil count (ANC) is greater than 1000 per mm 3 for 3 consecutive days, or per institutional standard. Treat severe infections [see Warnings and Precautions (5.1 , 5.4) ]. Monitor cardiopulmonary and renal functions throughout the treatment course. [see Warnings and Precautions (5.1 , 5.5 , 5.6 , 5.7) ]. Administer in an inpatient hospital setting. An intensive care facility and specialists skilled in cardiopulmonary or intensive care medicine must be available [see Dosage and Administration (2.1) , and Adverse Reactions (6.1) ] . WARNING: TREATMENT-RELATED MORTALITY, PROLONGED SEVERE CYTOPENIA, SEVERE INFECTION, CARDIOPULMONARY and RENAL IMPAIRMENT See full prescribing information for complete boxed warning. Monitor patients for prolonged severe cytopenia and monitor for internal organ hemorrhage ( 5.1 , 5.2 , 5.3 ) Treat severe infections ( 5.1 , 5.4 ) Monitor cardiopulmonary and renal functions throughout the treatment course ( 5.1 , 5.5 , 5.6 , 5.7 ) Administer in an inpatient hospital setting. An intensive care facility and specialists skilled in cardiopulmonary or intensive care medicine must be available ( 2.1 , 6.1 )

Description

11 DESCRIPTION AMTAGVI (lifileucel) is a tumor-derived autologous T cell immunotherapy comprised of a suspension of tumor-derived T cells for intravenous infusion. AMTAGVI is manufactured from resected patient tumor tissue prosected from one or more tumor lesions. Immune cells derived from a patient's tumor(s) are expanded in cell culture, washed, formulated as a cell suspension, and cryopreserved. The product must pass a sterility test before release for shipping as a frozen suspension in 1 to 4 patient-specific infusion bag(s) in individual protective metal cassettes. The product is thawed prior to administration back into the same patient [see Dosage and Administration (2.2) , How Supplied/Storage and Handling (16) ] . AMTAGVI is composed primarily of T cells of the CD4+T and CD8+T cell lineages. AMTAGVI may also contain monocytes and other lymphocytes, including B cells and NK cells. AMTAGVI may contain viable melanoma tumor cells from the original tumor tissue used to manufacture the product. The formulation contains 48% PlasmaLyte A, 50% CryoStor CS10 (resulting in final concentration of 5% dimethyl sulfoxide (DMSO)), 2% of 25% human serum albumin (resulting in a final concentration of 0.5% albumin), and 300 IU/mL IL-2 (aldesleukin). A single dose of AMTAGVI is provided in 1 to 4 infusion bag(s) containing 100 mL to 125 mL of viable cells per bag in individual protective cassettes.

What Is Lifileucel Used For?

1 INDICATIONS AND USAGE AMTAGVI is a tumor-derived autologous T cell immunotherapy indicated for the treatment of adult patients with unresectable or metastatic melanoma previously treated with a PD-1 blocking antibody, and if BRAF V600 mutation positive, a BRAF inhibitor with or without a MEK inhibitor. This indication is approved under accelerated approval based on objective response rate (ORR) [see Clinical Studies (14) ] . Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s). AMTAGVI is a tumor-derived autologous T cell immunotherapy indicated for the treatment of adult patients with unresectable or metastatic melanoma previously treated with a PD-1 blocking antibody, and if BRAF V600 mutation positive, a BRAF inhibitor with or without a MEK inhibitor. This indication is approved under accelerated approval based on objective response rate (ORR). Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s) ( 1 )

Dosage and Administration

2 DOSAGE AND ADMINISTRATION For autologous use only. For intravenous use only. Verify the patient's identity prior to infusion. For autologous use only. For intravenous use only. Verify the patient's identity prior to infusion. Administer AMTAGVI in an inpatient hospital setting with an intensive care facility ( 2.1 ) The AMTAGVI dose is between 7.5 × 10 9 and 72 × 10 9 viable cells ( 2.1 ) Administer a lymphodepleting regimen before infusion of AMTAGVI ( 2.2 ) Do NOT use a leukocyte depleting filter with AMTAGVI ( 2.2 ) Premedicate the patient with acetaminophen, or equivalent, and diphenhydramine, or another H1-antihistamine ( 2.2 ) Avoid prophylactic use of systemic corticosteroids ( 2.2 ) Administer entire dose of AMTAGVI ( 2.2 ) Administer IL-2 (aldesleukin) after infusion of AMTAGVI ( 2.2 ) See Full Prescribing Information for instructions on receipt, preparation, and administration of AMTAGVI ( 2.2 , 16 ) 2.1 Dose Administer in an inpatient hospital setting under the supervision of a physician experienced in the use of anticancer agents. An intensive care facility and specialists skilled in cardiopulmonary or intensive care medicine must be available. AMTAGVI is provided as a single dose for infusion containing a suspension of tumor-derived T cells. The dose is supplied in 1 to 4 patient-specific IV infusion bag(s) in individual protective metal cassettes. Each dose contains 7.5 × 10 9 to 72 × 10 9 viable cells. 2.2 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...

Side Effects (Adverse Reactions)

6 ADVERSE REACTIONS The most common (incidence of greater than or equal to 20%) non-laboratory adverse reactions in order of decreasing frequency were chills, pyrexia, fatigue, tachycardia, diarrhea, febrile neutropenia, edema, rash, hypotension, alopecia, infection, hypoxia, and dyspnea. The serious adverse reactions included: Treatment-Related Mortality [see Warnings and Precautions (5.1) ] Prolonged Severe Cytopenia [see Warnings and Precautions (5.2) ] Internal Organ Hemorrhage [see Warnings and Precautions (5.3) ] Severe Infection [see Warnings and Precautions (5.4) ] Cardiac Disorder [see Warnings and Precautions (5.5) ] Respiratory Failure [see Warnings and Precautions (5.6) ] Acute Renal Failure [see Warnings and Precautions (5.7) ] Hypersensitivity Reactions [see Warnings and Precautions (5.8) ] The most common (incidence of greater than or equal to 20%) non-laboratory adverse reactions in order of decreasing frequency were chills, pyrexia, fatigue, tachycardia, diarrhea, febrile neutropenia, edema, rash, hypotension, alopecia, infection, hypoxia, and dyspnea ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Iovance Biotherapeutics, Inc. at 1-833-400-IOVA (4682) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The pooled safety data described in this section reflect exposure to AMTAGVI within a regimen that included cyclophosphamide, fludarabine, and IL-2 (aldesleukin) in the global, multicenter, multicohort, open-label, single-arm clinical study in which 156 adult patients with unresectable or metastatic melanoma received a single infusion of AMTAGVI [see Clinical Studies (14) ] . The median age of the study population was 56 years (range: 20 to 79 years); 53.8% were men. The performance status prior to tumor procurement was 68.6% with ECOG 0 and 31.4% with ECOG 1. Table 1 summarizes the adverse reactions that occurred in at least 10% of patients treated with AMTAGVI and Table 2 describes the laboratory abnormalities of Grade 3 or 4 that occurred in at least 10% of patients. Table 1: Adverse Reactions Observed in at Least 10% of Melanoma Patients Treated with AMTAGVI (N=156) Adverse Reaction Any Grade n (%) Grade 3 or Higher n (%) Adverse Reactions occurred from AMTAGVI infusion to 6 months (182 days) post infusion. Blood and lymphatic system disorders Febrile neutropenia 73 (46.8) 73 (46.8) Cardiac disorders Tachycardia Tachycardia includes tachycardia and sinus tachycardia, atrial fibrillation, supraventricular tachycardia. 74 (47.4) 12 (7.7) Gastrointestinal disorders Diarrhea 73 (46.8) 3 (1.9) Vomiting 68 (43.6) 2 (1.3) Nausea 107 (68.6) 4 (2.6) General disorders and administration site conditions Chills 118 (75.6) 8 (5.1) Pyrexia 95 (60.9) 16 (10.3) Fatigue Fatigue includes fatigue, asthenia, and malaise. 87 (55.8) 8 (5.1) Edema Edema includes edema, face edema, generalized edema, localized edema, edema peripheral, peripheral swelling, edema genital, scrotal edema, brain edema, catheter site edema, conjunctival edema, eyelid edema, laryngeal edema, macular edema, periorbital edema, pulmonary edema, vasogenic cerebral edema, and lymphoedema. 66 (42.3) 8 (5.1) Investigations Weight increased 30 (19.2) 2 (1.3) Infections and Infestations 42 (26.9) 21 (13.5) Infection with pathogen unspecified Infection with unspecified pathogen includes cellulitis, conjunctivitis, cystitis, dermatitis infected, device related infection, diarrhea infectious, endocarditis, enterocolitis infectious, infection, meningitis, nasopharyngitis, neutropenic sepsis, pneumonia, pyuria, rash pustular, respiratory tract infection (RTI), rhinitis, sepsis, sinusitis, skin infection, urinary tract infection (UTI). 30 (19.2) 17 (10.9) Infection with...

Contraindications

4 CONTRAINDICATIONS None. None ( 4 )

Pregnancy and Breastfeeding

8.1 Pregnancy Risk Summary There are no available data with AMTAGVI use in pregnant women. No animal reproductive and developmental toxicity studies have been conducted with AMTAGVI. Therefore, AMTAGVI is not recommended for women who are pregnant, and pregnancy after AMTAGVI administration should be discussed with the treating physician. Report pregnancies to Iovance Biotherapeutics, Inc. at 1-833-400-IOVA. In the U.S. general population, the estimated risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

How Supplied

16 HOW SUPPLIED/STORAGE AND HANDLING AMTAGVI is supplied in 1 to 4 infusion bag(s) (NDC 73776-001-11), with each bag containing approximately 100 mL to 125 mL of frozen suspension of tumor-derived T cells in 5% DMSO, 0.5% albumin (human), and 300 IU/mL IL-2 (aldesleukin). Each bag is contained within a protective metal cassette (NDC 73776-001-12). AMTAGVI is stored in the vapor phase of liquid nitrogen and supplied in a liquid nitrogen cryoshipper. Product and patient-specific labels are located on both the product infusion bag(s) and the protective shipping 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 cassette(s) and infusion bag(s) on the shipment packing slip. Store AMTAGVI frozen in the vapor phase of liquid nitrogen (less than or equal to minus 150°C). Thaw AMTAGVI immediately prior to infusion [see Dosage and Administration (2.2) ] .

About This Information

This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.

What are side effects?

Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.

What are drug interactions?

Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.