AMTAGVI Dosage & Rx Info | Uses, Side Effects

Amtagvi Generic Name & Formulations

Legal Class

General Description

Lifileucel (contains 7.5×10^9 to 72×10^9 per dose in 1 to 4 infusion bags); cell susp for IV infusion; contains dimethyl sulfoxide (DSMO), albumin (human), IL-2 (aldesleukin).

Pharmacological Class

Tumor-derived autologous T cell immunotherapy.

How Supplied

Infusion bag (approx. 100–125mL)—1 to 4

Storage

Store Amtagvi frozen in the vapor phase of liquid nitrogen (less than or equal to minus 150°C). Thaw immediately prior to infusion.

Manufacturer

Iovance Biotherapeutics, Inc.

Generic Availability

Mechanism of Action

While the exact mechanism of action is unknown, Amtagvi is designed to deploy patient-specific T cells called tumor infiltrating lymphocyte (TIL) to locate and attack cancer cells.

Amtagvi Indications

Indications

In adults 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.

Amtagvi Dosage and Administration

Adult

For autologous and IV use only; confirm patient identity and availability of IL-2 (aldesleukin) prior to infusion. Do not use a leukodepleting filter. Give lymphodepleting chemotherapy (cyclophosphamide 60mg/kg IV + mesna daily for 2 days, then fludarabine 25mg/m² IV daily for 5 days) prior to Amtagvi infusion. Premedicate with APAP and diphenhydramine (or other H₁-antihistamine) approx. 30–60mins prior to Amtagvi infusion; avoid prophylactic corticosteroids. Infuse Amtagvi after 24hrs have elapsed after the last dose of fludarabine (no later than 4 days). Each dose contains 7.5×10⁹ to 72×10⁹ viable cells (1 to 4 infusion bags). Infuse contents of each bag within 3hrs of thawing. Initially infuse at approx. 1mL/min for the initial 5mins, then 5–10mL/min. Starting 3–24hrs after Amtagvi infusion: give IL-2 (aldesleukin) IV at 600,000 IU/kg every 8–12hrs for up to max 6 doses to support cell expansion in vivo.

Children

Not established.

Amtagvi Contraindications

Not Applicable

Amtagvi Boxed Warnings

Boxed Warning

Treatment-related mortality. Prolonged severe cytopenia. Severe infection. Cardiopulmonary. Renal impairment.

Amtagvi Warnings/Precautions

Warnings/Precautions

Administer under the supervision of an experienced physician. Have cardiopulmonary specialists or intensive care medicine available. Treatment-related mortality due to severe infections (sepsis, pneumonia, encephalitis), internal organ hemorrhage (abdominal hemorrhage, intracranial hemorrhage), acute renal failure, acute respiratory failure, cardiac arrythmia, extensive ascites, liver injury, and bone marrow failure. Monitor for infection, cardiac disorder, respiratory failure, acute renal failure, and severe reaction before and after infusion. Withhold or discontinue if internal organ hemorrhage, severe cardiac disorder, severe acute respiratory failure, or severe acute renal injury is indicated, or if patient is deemed ineligible for IL-2 infusion. Monitor CBCs after infusion. Avoid in those with clinically significant systemic infections. Pregnancy: not recommended; exclude status prior to initiation. Nursing mothers.

Amtagvi Pharmacokinetics

See Literature

Amtagvi Interactions

Interactions

Avoid anticoagulants if persistent or repeated thrombocytopenia occurs after infusion; monitor closely if unavoidable.

Amtagvi Adverse Reactions

Adverse Reactions

Chills, nausea, pyrexia, fatigue, tachycardia, diarrhea, vomiting, febrile neutropenia, edema, rash, hypotension, alopecia, decreased appetite, infection, hypoxia, dyspnea, headache, Grades 3 or 4 lab abnormalities; hypersensitivity reactions, infusion reactions.

Amtagvi Clinical Trials

Clinical Trials

The approval was based on data from the phase 2 C-144-01 study (ClinicalTrials.gov Identifier: NCT02360579), which evaluated lifileucel in adults with unresectable or metastatic melanoma who were previously treated with at least 1 systemic therapy, including a PD-1 blocking antibody, and if BRAF V600 mutation-positive, a BRAF inhibitor or BRAF inhibitor with or without MEK inhibitor.

The primary efficacy analysis included 73 patients who received lifileucel within the recommended dosing range of 7.5×10⁹ to 72×10⁹ viable cells; all patients had received prior anti-PD-(L)1 therapy, 63 received prior anti-CTLA-4 therapy, 42 received anti-PD1/anti-CTLA-4 combination therapy and 20 received a BRAF inhibitor or combination therapy with BRAF and MEK inhibitors.

Among the 73 patients, the objective response rate was 31.5% (95% CI, 21.1-43.4), with 3 complete responses and 20 partial responses. Median time to initial response was 1.5 months. Median duration of response was not reached, with 56.5%, 47.8%, and 43.5% of responders having responses lasting for at least 6, 9, and 12 months, respectively.

Amtagvi Note