Profile
General Information
Amtagvi ((lifileucel) is a tumor-derived autologous T cell immunotherapy.
Aimtagvi is specifically 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.
Dosing/Administration
Amtagvi is supplied as a suspension for intravenous administration. Amtagvi is for autologous use only.
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 x 109 to 72 x 109 viable cells.
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/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.
Administration: Administer entire dose of 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.
Administer IL-2 (aldesleukin) after infusion.
See Full Prescribing Information for specific instructions on receipt, preparation, and administration of Amtagvi.
Mechanism of Action
Amtagvi (lifileucel) is a tumor-derived autologous T cell immunotherapy comprised of a suspension of tumor-derived T cells for intravenous infusion. The exact mechanism of action is unknown. The proposed mechanism for Amtagvi offers a new cell therapy approach that deploys patient-specific T cells called TIL cells. When cancer is detected, the immune system creates TIL cells to locate, attack, and destroy cancer. TIL cells recognize distinctive tumor markers on the cell surface of each person’s cancer.
Side Effects
Adverse effects associated with the use of Amtagvi may include, but are not limited to, the following:
- chills
- pyrexia
- fatigue
- tachycardia
- diarrhea
- febrile neutropenia
- edema
- rash
- hypotension
- alopecia
- infection
- hypoxia
- dyspnea
The Amtagvi drug label comes with the following Black Box Warning for treatment-related mortality, prolonged severe cytopenia, severe infection, cardiopulmonary and renal impairment. Monitor patients for prolonged severe cytopenia and monitor for internal organ hemorrhage. Treat severe infections and monitor cardiopulmonary and renal functions throughout the treatment course.
Clinical Trial Results
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.
The FDA approval of Amtagvi was based on safety and efficacy results from the C-144-01 clinical trial. The global, multicenter trial investigated Amtagvi
in patients with advanced melanoma previously treated with anti-PD-1 therapy and targeted therapy, where applicable. Amtagvi
demonstrated deep and durable responses. The primary efficacy analysis set included 73 patients from Cohort 4 who received the recommended Amtagvi
dose from an approved manufacturing facility. Among the 73 patients, 31.5% achieved an objective response by Response Evaluation Criteria in Solid Tumors (RECIST 1.1) with a median duration of response not reached at 18.6 months follow-up2 (43.5% of responses had a duration greater than 12 months). Additionally, the supporting pooled efficacy set included a total of 153 patients from Cohort 4 and Cohort 2. Among the 153 patients, 31.4% achieved an objective response by RECIST 1.1 with a median duration of response not reached at 21.5 months follow-up2 (54.2% of responses had a duration greater than 12 months).