FDA Accepts Lifileucel's BLA for Advanced Melanoma With Priority Review


The BLA has a PDUFA action date of November 25, 2023.

The FDA has accepted for filing a biologics license application (BLA) for Iovance Biotherapeutics’ lifileucel (LN-144), an investigational autologous tumor infiltrating lymphocyte (TIL) therapy intended to treat advanced melanoma.1 

The BLA was accepted with priority review, with a PDUFA action date set for November 25, 2023. The company reported that the FDA did not request an advisory committee meeting for the BLA and stated that the agency indicated it has not noted any potential issues following preliminary review of the application. The FDA’s acceptance of the rolling BLA comes approximately 2 months after its submission was completed in March 2023.2 Iovance Therapeutics originally intended to complete the submission in the fourth quarter of 2022 but encountered a delay after the FDA requested supplemental validation information and comparability data on the therapy.3

“The BLA acceptance is a significant milestone in our mission to deliver lifileucel as the first individualized, 1-time cell therapy for a solid tumor,” Frederick Vogt, PhD, JD, the interim president and CEO of Iovance, said in a statement.1 “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 precommercialization activities and advancing our robust TIL pipeline.”

Lifileucel, which is intended for the treatment of patients with advanced melanoma who have progressed on or after anti-PD-1/L1 therapy and targeted therapy, previously received regenerative medicine advanced therapy designation from the FDA. Iovance Biotherapeutics noted that there are currently no FDA-approved treatments for patients in lifileucel’s indicated setting.

The company’s BLA submission is supported by results from the phase 2 C-144-01 (NCT02360579) clinical trial, data from which were presented by Amod A. Sarnaik, MD, FACS, of Moffitt Cancer Center and the University of South Florida, at the Society for Immunotherapy of Cancer’s (SITC) 37th Annual Meeting, held November 8-12, 2022, in Boston, Massachusetts.4 The multicenter study consists of 4 cohorts and is the largest ever study of a TIL therapy in advanced melanoma for patients previously treated with immune checkpoint inhibitors. Sarnaik presented pooled data, which had a cutoff date of July 15, 2022, that came from patients in cohorts 2 (n = 66) and 4 (n = 87). Among the key efficacy results were an independent review committee-assessed objective response rate of 31.4%, with 9 complete responses and 39 partial responses; a median overall survival (OS) of 13.9 months; and a 12-month OS rate of 54% (95% CI: 45.6%, 61.6%).

In addition to C-144-01, lifileucel is also being evaluated in a randomized phase 3 clinical trial entitled TILVANCE-301(NCT05727904), which is currently recruiting patients. Iovance Biotherapeutics noted that if lifileucel receives accelerated approval, TILVANCE-301 may transition into a confirmatory trial to support the therapy’s full approval. The company anticipates that TILVANCE-301 will be in full swing by the time of lifileucel’s PDUFA date.

In November 2022, CGTLiveinterviewed Sarnaik about the current treatment landscape for advanced melanoma and where lifileucel could fit into this landscape if it becomes an approved therapy. He noted some of the infrastructural limitations that currently make cell therapy options less accessible for patients than more conventional treatments.

“There are definitely challenges associated with implementation of a product as complex as lifileucel,” Sarnaik said. “This requires mobilization of resources that as a medical field we're not quite used to. The treatment does involve extensive patient and caregiver education, as well as mobilization of resources associated with practitioners of surgical oncology, medical oncology, as well as cellular therapy. Of note, cellular therapy is still a relatively emerging field, and therefore represents a relatively scarce resource.”

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. https://ir.iovance.com/news-releases/news-release-details/iovance-biotherapeutics-announces-us-food-and-drug
2. Iovance Biotherapeutics completes biologics license application (BLA) submission for lifileucel in advanced melanoma. News release. Iovance Biotherapeutics. March 24, 2023. Accessed May 30, 2023. https://finance.yahoo.com/news/iovance-biotherapeutics-completes-biologics-license-200100220.html
3. Iovance Biotherapeutics provides update on biologics license application submission for lifileucel in advanced melanoma. News release. Iovance Biotherapeutics. November 18, 2022. Accessed May 30, 2023. https://finance.yahoo.com/news/iovance-biotherapeutics-provides-biologics-license-113000414.html
4. Sarnaik A. Lifileucel TIL cell monotherapy in patients with advanced melanoma after progression on immune checkpoint inhibitors (ICI) and targeted therapy: Pooled analysis of consecutive cohorts (C-144-01 study). Presented at: Society for Immunotherapy of Cancer’s (SITC) 37th Annual Meeting November 8-12, 2022; Boston, Massachusetts. #789
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