FDA Delays BLA for Lifileucel in Patients With Advanced Melanoma

Additional data is needed for lifileucel before it is granted a biologics license application by the FDA for patients with unresectable or metastatic melanoma.

The FDA has delayed a biologics license application (BLA) for lifileucel (LN-144), a treatment for unresectable or metastatic melanoma, until the start of 2023 due to a request for additional data on the agent.1

According to Iovance Biotherapeutics, the FDA has requested the company address comparability data between manufacturing sites that were involved in the studies.

“What the FDA is asking for is relatively straightforward. It shouldn’t be difficult to get it to the FDA in the first quarter of 2023,” said Frederick Vogt, PhD, JD, interim president and chief executive officer of Iovance, in the press release.

Lifileucel is a tumor-infiltrating lymphocyte (TIL) treatment for use in patients with unresectable or metastatic melanoma whose disease has progressed on or after prior anti-PD-1 or PD-L1 therapy and targeted BRAF/MEK inhibitor therapy. Currently, there are no FDA-approved therapies in this patient population.

Previously in August 2022, a rolling submission of the BLA for lifileucel was initiated to the FDA based on findings of the phase 2 C-144-01 trial (NCT02360579) which assessed the efficacy and safety of the TIL therapy lifileucel in this patient population.

In a presentation on the trial in November 2022 at the Society for Immunotherapy of Cancer (SITC) Annual Meeting, data showed there to be clinically meaningful and durable activity with lifileucel when given to patients with melanoma after progression on immune checkpoint inhibitors.

Pooled consecutive cohorts from the C-144-01 trial (NCT02360579) examined efficacy data from a total of 153 patients with advanced melanoma. A total of 66 patients were enrolled in cohort 2, 87 were in cohort 4, and all patients had progressed on or after receiving prior immune checkpoint inhibitor therapy and targeted BRAF/MEK therapy.2

The primary end point of the trial is objective response rate (ORR) with secondary end points of disease assessment for duration of response, disease control rate (DCR), progression-free survival, overall survival (OS), and adverse events (AEs).

At baseline, patients were heavily pre-treated with a median of 3 lines of prior therapy (range, 1-9) and had substantial disease burden at baseline. Further, 100% of patients had received previous anti-PD-1 therapy and more than 80% of patients received prior anti-CTLA-4 treatment.

Findings revealed that the ORR assessed by an independent review committee using RECIST v1.1 was 31% (95% CI, 24.1%-39.4%). There were 8 complete responses, 40 partial responses, but the median DOR was not reached. Among responses, 42% extended beyond 18 months, and 40% of responses were ongoing at the median follow-up of the study at 27.6 months.

In patients who achieved a response at their first assessment, the median OS was 13.9 months (95% CI, 10.6-17.8) and had not been reached (95% CI, 22.5-not reached). The safety profile of the agent was consistent with the underlying disease and known AE profiles of nonmyeloablative lymphodepletion and IL-2.

A phase 3 study of the agent in combination with pembrolizumab (Keytruda) in patients with frontline advanced melanoma is expected to launch before the end of 2022 as a confirmatory trial for expected accelerated approval of lifileucel. According to Vogt, the FDA wants a confirmatory trial to be well-underway.

“[The FDA seems] very comfortable with our timelines. It’s been very positive, and whatever they mean by 'well-underway,' we will be on top of it at the time of submission,” added Vogt in the press release.

Iovance's BLA for advanced melanoma therapeutic delayed until Q1 2023. News release. Iovance Biotherapeutics, Inc. November 18, 2022. Accessed November 21, 2022. https://bit.ly/3EtCSDg
Iovance Biotherapeutics announces updated clinical data for lifileucel in advanced melanoma at society for immunotherapy of cancer (SITC) annual meeting. News release. Iovance Biotherapuetics, Inc. November 7, 2022. Accessed November 21, 2022. https://bit.ly/3tNIp2A