FDA Gives Priority Review to BLA for Lifileucel in Advanced Melanoma

The FDA has given priority review to a biologics license application (BLA) for lifileucel (LN-144) in the treatment of patients with advanced melanoma, according to a press release from Iovance Biotherapeutics, Inc.¹

"The trial demonstrated a robust and clinically meaningful response rate and long-term durability following one-time treatment," according to an expert from H. Lee Moffitt Cancer Center.

The FDA has set a Prescription Drug User Fee Act date of November 25, 2023 for lifileucel in this patient population. The agency does not have any plans to hold an advisory committee meeting to discuss the application and has not identified any potential review issues following a preliminary review.

“The FDA’s commitment to a 6-month priority review validates the unmet need and urgency for new treatment options for patients with advanced melanoma who have progressed on or after standard of care therapies,” Frederick Vogt, PhD, JD, interim president and chief executive officer at Iovance, said in the press release.

The BLA for lifileucel in this patient population was supported by findings from the phase 2 C-144-01 trial, in which investigators reported an overall response rate (ORR) of 31.4% (95% CI, 24.1%-39.4%), including 9 complete responses (CRs) and 39 partial responses (PRs) among those receiving the agent.² Additionally, 7 patients had initial PRs that converted into CRs, including 1 conversion over 10 months since the initial data analysis.

The median duration of response (DOR) was not reached (NR), and responses lasted for 24 months or longer in 41.7% of those with a response, including 47.8% of those in cohort 2 and 36.0% of those in cohort 4. The median overall survival (OS) was NR (95% CI, 30.4-NR) for those who had a response at first assessment and 13.9 months (95% CI, 10.6-17.8) for all patients. Investigators observed responses across all subgroups, including those with immune checkpoint inhibitor (ICI) primary-resistant disease, those who received prior anti–CTLA-4 therapy and/or targeted therapies, and in patients regardless of PD-L1 status.

Treatment-emergent adverse effects (TEAEs) in the trial were consistent with the known AE profiles of nonmyeloablative lymphodepletion and interleukin-2 (IL-2). The rates of TEAEs decreased within the first 2 weeks after patients underwent lifileucel infusion.

“The trial demonstrated a robust and clinically meaningful response rate and long-term durability following one-time treatment,” lead trial investigator Amod Sarnaik, MD, professor of Cutaneous Oncology and Immunology at H. Lee Moffitt Cancer Center, said at the time of the updated clinical data analysis for the C-144-01 trial. “We hope to offer lifileucel to many more patients after initial progression on [ICIs].”

Investigators of the prospective phase 2 C-144-01 trial assessed lifileucel, an autologous adoptive cell transfer therapy, in the treatment of those with metastatic melanoma. Treatment involved patients receiving a lymphocyte depleting preconditioning regimen prior to infusion of lifileucel, followed by IL-2.

The primary end point of the trial was ORR. Secondary end points included DOR, disease control rate, progression-free survival, OS, and AEs.

Patients 18 years and older with stage IIIc or IV melanoma and disease progression following at least 1 prior systematic therapy including a PD-1 antibody were eligible for enrollment on the trial. Additional inclusion criteria included having at least 1 measurable lesion per RECIST v1.1 criteria, an ECOG performance status of 0 or 1, and a life expectancy of at least 3 months.

Investigators presented data from the phase 2 C-144-01 trial in a rapid oral presentation at the 2022 Society for Immunotherapy of Cancer (SITC) Annual Meeting.

If lifileucel receives accelerated approval in the treatment of advanced melanoma, investigators plan to initiate the randomized phase 3 TILVANCE-301 trial (NCT05727904) as a confirmatory study to support full approval for the agent. In the TILVANCE-301 trial, investigators will compare lifileucel plus pembrolizumab (Keytruda) vs pembrolizumab with optional crossover to lifileucel monotherapy among patients with untreated, unresectable, or metastatic melanoma.

References

1. 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. Iovance Biotherapeutics, Inc. May 26, 2023. Accessed May 30, 2023. bit.ly/3OOSHLA
2. Iovance Biotherapeutics announces updated clinical data for lifileucel in advanced melanoma at Society for Immunotherapy of Cancer (SITC) Annual Meeting. News release. Iovance Biotherapeutics, Inc. November 10, 2022. Accessed May 30, 2023. bit.ly/3WFuBEW