FDA Accepts BLA of Lifileucel for Advanced Melanoma

• A Prescription Drug User Fee Act action date of November 25, 2023 has been set for a decision on the biologics license application (BLA) for lifileucel as treatment of advanced melanoma.

• No advisory committee meeting is planned to discuss the BLA.

• If approved, lifileucel will become the first individualized, 1-time cell therapy for this patient population.

The FDA has accepted the BLA and granted priority review for lifileucel for patients with advanced melanoma, according to iovance Biotherapeutics, Inc.¹

“The BLA acceptance is a significant milestone in our mission to deliver lifileucel as the first individualized, one-time cell therapy for a solid tumor. 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. I am grateful for the patients and physicians who took part in all our clinical trials, as well as the Iovance team for their outstanding work on our first BLA filing. We look forward to continuing our collaboration with the FDA during the BLA review cycle, while continuing to execute our pre-commercialization activities and advancing our robust TIL pipeline,” said Frederick Vogt, PhD, JD, interim president and chief executive officer of Iovance, in a press release.

Lifileucel is a TIL therapy designed for patients with advanced melanoma who progressed on or after prior anti-PD-1/L1 therapy and targeted therapy, where applicable.

Positive data from the C-144-01 clinical trial (NCT02360579)which evaluated the agent in patients with advanced melanoma who progressed on or after prior anti-PD-1/L1 therapy and targeted therapy were the basis of this BLA submission. In the C-144-01 trial, efficacy data from 153 patients with advanced melanoma enrolled in cohort 2 (n = 66) and cohort 4 (n = 87) were evaluated. At a data cutoff date of July 15, 2022, the median study follow up was 36.5 months. In order to be eligible for enrollment, patients must have progressed on or after immune checkpoint inhibitor (ICI) therapy and targeted BRAF/MEK inhibitor therapy.²

Lifileucel led to an overall response rate of 31.4% (95% CI, 24.1%-39.4%) with 9 complete responses (CR) and 39 partial responses (PR), and the median duration of response was not reached at 36.5 months. A total of 42% of responses lasted for 24 months or more.

The median time from lifileucel infusion to best response was 1.5 months. Responses among patients deepened over time. Seven patients who had initial PRs converted to CRs as late as 2 or more years after receiving lifileucel, including 1 conversion to CR in approximately 10 months since the initial data analysis in the abstract.

Additionally, treatment-emergent adverse events (TEAEs) were consistent with the known AE profiles of nonmyeloablative lymphodepletion and interleukin-2. The incidence of TEAEs rapidly decreased within the first 2 weeks following lifileucel infusion.

If given accelerated approval, the randomized phase 3 TILVANCE-301 trial (NCT05727904) of lifileucel in patients with frontline advanced melanoma will serve as the confirmatory study to support full approval. It is expected that this trial will be well underway at the time of approval.

REFERENCES:

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. https://tinyurl.com/2ku25fnv

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. https://tinyurl.com/4yfc2h4d