The FDA has extended the priority review period for the biologics license application seeking the approval of the tumor infiltrating lymphocyte therapy lifileucel for the treatment of patients with advanced melanoma who progressed on or after anti–PD-1/PD-L1 therapy and targeted therapy.
The FDA has extended the priority review period for the biologics license application (BLA) seeking the approval of the tumor infiltrating lymphocyte (TIL) therapy lifileucel (LN-144) for the treatment of patients with advanced melanoma who progressed on or after anti–PD-1/PD-L1 therapy and targeted therapy.1
The regulatory agency needs additional time due to resource constraints, according to an announcement from Iovance Biotherapeutics. The FDA told Iovance that the agency had insufficient resources to review a recent response to an information request for the ongoing BLA review prior to the planned late-cycle review meeting scheduled for September 11, 2023. In a subsequent meeting on September 14, 2023, the FDA pointed to resource constraints and agreed to work closely with Iovance to expedite the remaining review.
After receiving an initial target action date of November 25, 2023, under the Prescription Drug User Fee Act (PDUFA), the updated PDUFA date is February 24, 2024.1,2
“While the resource constraints at FDA have extended our PDUFA date, Iovance and FDA remain engaged to complete the review process as quickly as possible. We appreciate FDA management’s efforts to expedite the remaining review so that we can bring lifileucel to critically ill patients with no other FDA approved options after current standard of care,” Frederick Vogt, PhD, JD, interim president and chief executive officer of Iovance, stated in a news release. “We are confident in the potential for lifileucel to redefine the treatment paradigm for these patients. With the strength of our clinical data, manufacturing capabilities, and commercial readiness efforts, Iovance is well positioned to rapidly serve the U.S. melanoma community immediately following an approval.”
The BLA was supported by data from cohort 2 (n = 66) and cohort 4 (n = 87) of the phase 2 C-144-01 trial (NCT02360579). Pooled data from both cohorts showed that patients who had progressed on or after immune checkpoint inhibitor therapy or, when appropriate, targeted BRAF/MEK inhibitor therapy achieved an overall response rate (ORR) of 31.4% (95% CI, 24.1%-39.4%). Nine patients experienced a complete response (CR), and 39 patients had a partial response (PR).3
The median time from lifileucel infusion to best response was 1.5 months. Seven patients improved from PR to CR as late as 2-plus years following treatment.
C-144-01 was an open-label, nonrandomized, multicenter study that enrolled patients at least 18 years of age with unresectable or metastatic melanoma who received at least 1 prior systemic therapy including an anti–PD-1 antibody and a BRAF inhibitor with or without a MEK inhibitor if they harbored a BRAF V600 mutation.4 Patients needed to have at least 1 tumor lesion 1.5 cm or more in diameter postresection for TIL generation and at least 1 target lesion for response assessment. An ECOG performance status of 0 or 1 was required, and there was no limit on prior therapy.
Patients in cohorts 2 and 4 received nonmyeloablative lymphodepletion, followed by a single infusion of cryopreserved lifileucel and up to 6 doses of interleukin-2 (IL-2).
The trial’s primary end point was ORR by independent review committee assessment per RECIST v1.1 criteria. Secondary end points included duration of response (DOR), progression-free survival, overall survival (OS), and safety.
Additional data from C-144-01 showed that the median DOR was not yet reached (NR). Furthermore, 41.7% of responders experienced responses of at least 24 months. Those rates were 47.8% and 36.0% for patients in cohorts 2 and 4, respectively.3
The median OS was NR (95% CI, 30.4-NR) in patients who experienced a response at 6 weeks. Among all patients, the median OS was 13.9 months (95% CI, 10.6-17.8).
Regarding safety, treatment-emergent adverse effects (TEAEs) were consistent with the underlying disease and known toxicity profiles of nonmyeloablative lymphodepletion and IL-2. Rates of TEAEs quickly fell within the first 2 weeks after lifileucel infusion.