Iovance to Address FDA Requests for BLA of Lifileucel in Advanced Melanoma

After receiving FDA feedback regarding supplemental assay validation information and comparability data for lifileucel in advanced melanoma, Iovance Biotherapeutics will address these comments and plans to complete its rolling biologics license application submission during the first quarter of 2023.

After receiving recent FDA feedback regarding supplemental assay validation information and comparability data for lifileucel (LN-44) in the treatment of advanced melanoma, Iovance Biotherapeutics will address these comments and plans to complete its rolling biologics license application (BLA) submission during the first quarter of 2023.1

In August 2022, the company submitted a rolling BLA to the FDA seeking the approval of lifileucel for the treatment of patients with advanced melanoma who progressed on or after previous anti–PD-1/PD-L1 therapy, and if BRAF mutation positive, also previous BRAF or BRAF/MEK inhibitor therapy.2

“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 investigational new drug application and remains supportive during the rolling BLA submission process,” Frederick Vogt, PhD, JD, interim president and chief executive officer of Iovance, stated in a press release. “Iovance is fully committed to securing FDA approval as soon as possible to deliver the first individualized, one-time cell therapy for advanced melanoma patients, who have a significant unmet medical need.”

The BLA for lifileucel, a tumor-infiltrating lymphocyte therapy, is based on findings from the phase 2 C-144-01 trial (NCT02360579).

Data showed that patients treated in cohort 4 (n = 87) achieved an objective response rate (ORR) of 29% (95% CI, 19.5%-39.4%) per independent review committee (IRC) assessment and by RECIST v1.1 criteria.3 Three patients experienced complete responses (CRs) and 22 had partial responses (PRs). At a median follow-up of 23.5 months, the median duration of response (DOR) in this cohort was 10.4 months by IRC.

In cohort 2 (n = 66), lifileucel elicited an ORR of 35% (95% CI, 23.5%-47.6%) per IRC, including 5 CRs and 18 PRs. The median DOR was not yet reached at a median follow-up of 36.6 months.

In pooled patients from cohorts 2 and 4 (n = 153), lifileucel produced an ORR of 31% (95% CI, 24.1%-39.4%) by IRC. At a median follow-up of 27.6 months, the median DOR was not yet reached.

Investigators enrolled patients with unresectable or metastatic stage IIIC or IV melanoma that was with confirmed radiologic progression.4 Patients were required to have progressed after 1 or more previous systemic therapies, including a PD-1 inhibitor, and if BRAF positive, a BRAF inhibitor with or without a MEK inhibitor.

Enrolled patients were administered a nonmyeloablative lymphodepletion regimen comprised of cyclophosphamide at 60 mg/kg once daily for 2 days followed by fludarabine at 25 mg/m2 once daily for 5 days. Lifileucel was thawed and administered as a single infusion about 24 hours from the last dose of fludarabine. A short course of bolus interleukin-2 at 600,000 IU/kg was infused every 8 to 12 hours for up to 6 doses, starting within 3 to 24 hours of completing the infusion.

Investigator-assessed ORR served as the trial’s primary end point. Secondary end points consisted of DOR, overall survival, and safety.

Treatment-emergent adverse effects experienced in both cohorts were consistent with the underlying disease and the known safety profiles of nonmyeloablative lymphodepletion and IL-2. Safety findings were similar between cohorts 2 and 4.

References

  1. Iovance Biotherapeutics provides update on biologics license application submission for lifileucel in advanced melanoma. News release. November 18, 2022. Accessed November 18, 2022. http://bit.ly/3TNGoya
  2. Iovance Biotherapeutics initiates biologics license application (BLA) submission for lifileucel in advanced melanoma. News release. Iovance Biotherapeutics, Inc. August 25, 2022. Accessed November 18, 2022. https://bit.ly/3QSNyR1
  3. Iovance Biotherapeutics announces positive clinical data for lifileucel in advanced melanoma. News release. Iovance Biotherapeutics, Inc. May 26, 2022. Accessed November 18, 2022. https://bit.ly/3RdbWMG
  4. Sarnaik AA, Hamid O, Khushalani NI, et al. Lifileucel, a tumor-infiltrating lymphocyte therapy, in metastatic melanoma. J Clin Oncol. 2021;39(24):2656-2666. doi:10.1200/JCO.21.00612