FDA OKs Lifileucel Treatment for Advanced Melanoma

• Lifileucel (Amtagvi; formerly LN-44) is a tumor infiltrating lymphocyte therapy for patients with advanced melanoma who progressed on or after anti-PD1/L1 therapy and/or targeted therapy.
• This marks the first FDA-approved therapy in this intent-to-treat (ITT) population.
• This decision comes after the FDA pushed back the Prescription Drug User Fee Act (PDUFA) target action date of November 25, 2023.

The FDA has approved lifileucel for the treatment of patients with advanced melanoma who have progressed following anti-PD1/L1 and/or targeted therapy, making it the first FDA-approved therapy for this patient population.¹

The approval is supported by findings from cohort 2 (n = 66) and cohort 4 (n = 87) of the phase 2 C-144-01 trial. Pooled data from both cohorts of the study found that patients who progressed on or after immune checkpoint inhibitor therapy or targeted BRAF/MEK inhibitor therapy demonstrated an overall response rate (ORR) of 31.4% (95% CI, 24.1%-39.4%). Additionally 8 patients experienced a complete response (CR), and 40 patients had a partial response (PR).

Further, the median time from lifileucel infusion to best response was 1.5 months and 6 patients improved from PR to CR as late as 2-plus years after treatment.

A biologics license application for lifileucel was accepted in May 2023, and was also supported by findings from the phase 2 C-144-01 trial and lifileucel was granted priority review and had a PDUFA target action date of November 25, 2023. Lifileucel was also granted a regenerative medicine advanced therapy designation. In September 2023, the FDA pushed back the target action date to February 24, 2024.

"Unresectable or metastatic melanoma is an aggressive form of cancer that can be fatal,” said Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research (CBER), in a press release.¹ “The approval of Amtagvi represents the culmination of scientific and clinical research efforts leading to a novel T-cell immunotherapy for patients with limited treatment options.”

Now, the phase 3 TILVANCE-301 trial (NCT05727904) is investigateing lifileucel plus pembrolizumab (Keytruda) vs pembrolizumab monotherapy in the ITT population.²

About TILVANCE-301

TILVANCE-301 is a phase 3, multicenter, open-label, trial with an estimated enrollment of 670 patients. Patients are randomized to 1 of 2 arms.³ Patients in arm A are receiving pembrolizumab followed by the lifileucel regimen of non-myeloablative lymphodepletion, lifileucel infusion, and interleukin-2. Patients in arm B are being treated with pembrolizumab monotherapy every 6 weeks until disease progression is observed.Patients in this arm then have the option to cross over to arm A.

The co-primary end points are ORR and progression-free survival. Secondary end points include overall survival, CR rate, duration of response, event-free survival, and incidence of adverse events.

To be eligible to participate, patients must have histologically or pathologically confirmed stage IIIC, IIID, or IV unresectable metastatic melanoma. They must also have an ECOG performance status of 0 or 1, a life expectancy of greater than 6 months, and adequate organ function. Patients are not eligible to participate if the melanoma is of uveal or ocular origin, if they have symptomatic untreated brain metastases, if they have received prior therapy for metastatic disease, or if they have a BRAF V600 mutation-positive tumor that received prior immune checkpoint inhibitor therapy.

“Melanoma is a life-threatening cancer that can cause devastating impacts to affected individuals, with a significant risk of metastasizing and spreading to other areas in the body,” said Nicole Verdun, MD, director of the Office of Therapeutic Products in CBER. “Today’s approval reflects the FDA’s dedication and commitment to the development of innovative, safe and effective treatment options for cancer patients.”

REFERENCES:

1. FDA approves first cellular therapy to treat patients with unresectable or metastatic melanoma. News release. FDA. February 16, 2024. Accessed February 16, 2024. http://tinyurl.com/5n7cuszk

2. Iovance Biotherapeutics announces U.S. Food and Drug Administration acceptance of the biologics license application of lifileucel for the treatment of advanced melanoma. News release. May 26, 2023. Accessed January 17, 2024. http://tinyurl.com/4wa23d3x

3. Study to investigate lifileucel regimen plus pembrolizumab compared with pembrolizumab alone in participants with untreated advanced melanoma. ClinicalTrials.gov. Updated January 24, 2024. Accessed January 24, 2024. https://clinicaltrials.gov/study/NCT05727904