The FDA has requested supplemental validation information and comparability data for the tumor-infiltrating therapy.
New FDA feedback has pushed back Iovance Biotherapeutics’ expected 2022 lifileucel biologics license application for treating melanoma to the first quarter of 2023. The FDA has requested supplemental validation information and comparability data for lifileucel, which the company will address “promptly”.1
“We continue to make substantial progress with our ongoing BLA submission and remain close to the finish line. The FDA has provided recent valuable feedback to the IND application and remains supportive during the rolling BLA submission process. Iovance is fully committed to securing FDA approval as soon as possible to deliver the first individualized, 1-time cell therapy for advanced melanoma patients, who have a significant unmet medical need,” Frederick Vogt, PhD, JD, interim president and chief executive officer, Iovance, said in a statement.1
Iovance had previously started the rolling BLA process in August 2022 after what the company stated was a successful pre-BLA meeting with the FDA.2 At that time, the company predicted the submission would be completed in the fourth quarter of 2022. The BLA is for lifileucel intended to treat unresectable or metastatic melanoma that progressed on or after prior anti-PD-1/L1 therapy, and if BRAF mutation positive, also prior BRAF or BRAF/MEK inhibitor therapy.
Lifileucel, a tumor-infiltrating lymphocyte (TIL) therapy, just recently demonstrated durable efficacy and manageable safety in updated data from the phase 2 C-144-01 clinical trial (NCT02360579) presented at the Society for Immunotherapy of Cancer’s (SITC) 37th Annual Meeting, November 8-12, 2022, in Boston, Massachusetts.3 The data were presented by study investigator Amod A. Sarnaik, MD, FACS, associate professor of cutaneous oncology and immunology, Moffitt Cancer Center. CGTLive recently spoke to both Sarnaik and study coauthor Omid Hamid, MD, chief, research and immunotherapy, Cedars-Sinai - The Angeles Clinic and Research Institute, about the new data.
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"Lifileucel is a 1-time therapy. The toxicity is manageable and usually related to the preconditioning or the IL-2. So, what you have is the ability to give a viable option to our patients that is a 1-time option and can give durability of response,” Hamid told CGTLive.
Lifileucel had an objective response rate of 31.4% in the 2 cohorts from which data were presented, with 9 complete responses and 39 partial responses. Median duration of response (DOR) was not reached at a median follow up of 36.5 months, and 41.7% of responding patients had a DOR of 24 months or more. Median overall survival (OS) was 13.9 months, and the 12-month OS rate was 54% (95% CI: 45.6%, 61.6%)
All participants experienced at least 1 treatment-emergent adverse event (TEAE) and 94.9% of patients experienced at least a single grade 3 or grade 4 TEAE. These included chills, pyrexia, febrile neutropenia, hypophosphatemia, hypotension, fatigue, and diarrhea. Most TEAEs were transient and consistent with lymphodepletion and IL-2. The incidence of TEAEs reduced rapidly within the first 2 weeks following treatment.
“[Responses to lifileucel were observed] across all subgroups analyzed, including BRAF mutational status and PDL-1 tumor proportion score,” Sarnaik said during his presentation.3 “Some of target lesion diameters above the median and elevated lactate dehydrogenase (LDH), both known negative prognostic factors, were each independently correlated with a lower response. Patients with some of target lesion diameters below the median and a normal LDH had a greater likelihood of response than those with either or both of these adverse factors being higher. This suggests that the earlier use of lifileucel in disease progression may provide a greater benefit for patients.”