Iovance plans to complete BLA submission for lifileucel by August 2022.
Iovance Biotherapeutics has received positive feedback from the FDA regarding their proposed potency assay and cell co-culture assays for its upcoming Biologics License Application (BLA) for lifileucel (LN-144) for the potential treatment of metastatic melanoma.1
“The favorable feedback received from the FDA on our potency assays and assay matrix brings Iovance a step closer to our submission of a BLA for lifileucel in metastatic melanoma,” Frederick Vogt, PhD, JD, interim president and chief executive officer, Iovance Biotherapeutics, said in a statment. “We look forward to bringing lifileucel to the market quickly to offer [patients with] melanoma a new option following anti–PD-1 therapy.”
The company expects to request a pre-BLA meeting in July 2022 and to complete BLA submission for lifileucel by August 2022.
Lifileucel is being evaluating in the prospective, open-label, multicohort, nonrandomized, multicenter phase 2 IOV-COM-202 trial (NCT03645928) in combination with pembrolizumab (Keytruda) in patients with immune checkpoint inhibitor–naïve advanced melanoma.2
The IOV-COM-202 trial is currently recruiting patients of at least 18 years of age that have received 3 lines or less of prior systemic therapy, have an ECOG performance status of 0 or 1, have at least 1 resectable lesion, and at least 1 measurable lesion following resection for response assessment.
Lifileucel is a tumor-infiltrating lymphocyte (TIL) therapy manufactured at centralized GMP facilities as part of a 22-day process. Patients receive non-myeloablative lymphodepletion chemotherapy with cyclophosphamide and fludarabine before infusion with up to 6 doses of interleukin-2. The first dose of pembrolizumab was given following tumor harvest and the agent was continued every 3 or 6 weeks following lifileucel.
The trial is primarily assessing objective response rate (ORR) according to RECIST v1.1 criteria as well as safety via grade 3 or higher treatment-emergent adverse effects (TEAEs).
The trial has enrolled 7 patients to cohort 1a as of the data cutoff date of April 29, 2021. Patients had a median age of 52.0 years (range, 34-59), 85.7% were female, 71.4% had an ECOG performance status of 0, and 85.7% had stage IV disease. Approximately 29% (28.6%) of patients received 1 prior line of systemic treatment, which could have included chemotherapy (14.3%), targeted therapy in the form of BRAF/MEK inhibition (14.3%), or other (14.3%).
Regarding BRAF mutational status, 14.3% had mutated V600E or V600K, 42.9% had wild-type disease, 14.3% had unknown status, and 28.6% had other status. Moreover, 57.1% of patients had a PD-L1 tumor proportion score of 5% or higher, 28.6% were PD-L1 negative, and 14.3% of patients had this information missing. Just under half, or 42.9%, of patients had elevated lactate dehydrogenase levels. Patients had high tumor burden with a mean sum of diameters of target lesions was 111.4 mm, and 85.7% of patients had more than 3 target and non-target lesions at baseline.
Previous data has demonsrated efficacy of the pembrolizumab/lifileucel combination. Data presented during the 2021 ASCO Annual Meeting showed that at a median follow-up of 8.2 months, the combination yielded an ORR of 85.7%, which included a complete response (CR) rate of 42.9% and a partial response (PR) rate of 42.9%. One patient achieved stable disease with the regimen and disease control rate was 100%.
The safety profile of the combination proved to be consistent with the underlying disease and the known profiles of pembrolizumab, non-myeloablative lymphodepletion, and IL-2. Notably, no unexpected toxicities were reported with pembrolizumab following TIL therapy.
Any-grade toxicities experienced with the combination included thrombocytopenia (100%), chills (85.7%), nausea (85.7%), pyrexia (85.7%), vomiting (85.7%), fatigue (71.4%), febrile neutropenia (71.4%), hypertension (57.1%), neutropenia (57.1%), alopecia (42.9%), cough (42.9%), decreased appetite (42.9%), and peripheral edema (42.9%).
The grade 3 or 4 effects reported with the regimen comprised thrombocytopenia (85.7%), pyrexia (28.6%), fatigue (14.3%), febrile neutropenia (71.4%), hypertension (57.1%), neutropenia (57.1%), and peripheral edema (14.3%).
Updated data on 12 patients in cohort 1A showed that the combination produced an ORR of 67%; this included 3 CRs and 5 PRs. Moreover, 6 of the 8 responders were noted to have continued response to treatment at the time of the last data cutoff, with 5 responders experiencing a duration of response of longer than 1 year.
Iovance has shared plans to open a phase 3 study examining frontline lifileucel in combination with pembrolizumab in patients with immune checkpoint inhibitor–naïve metastatic melanoma in late 2022.