Lifileucel Shows Long-Term Promise in Advanced Melanoma

Five-year follow-up data from the phase 2 C-144-01 study (NCT02360579) show that lifileucel (Amtagvi) maintained efficacy and favorable safety in pretreated patients with advanced melanoma,¹ showcasing the long-term promise of the 1-time autologous tumor-infiltrating lymphocyte (TIL) cell therapy.

A key insight from the data was the continued presence of durable, deepening responses. At the data cut-off date of November 20, 2024, the objective response rate (ORR) among the 153 patients who received a 1-time infusion of lifileucel across 2 cohorts was 31.4%, with 5.9% achieving complete response and 25.5% achieving partial response. The median time to response was 1.4 months (range, 1.3–4.2), and the median duration of response (DOR) was 36.5 months. Of the patients that responded (n = 48), 31.3% had ongoing responses at the time of the 5-year assessment. Additionally, tumor burden reduction occurred in 79.3% of patients.

In terms of survival, the median overall survival (OS) for the overall population was 13.9 months (95% CI, 10.6–17.8), and the 5-month OS rate was 19.7%.

Safety data revealed that lifileucel maintained a safety profile that was consistent with the known safety profile of nonmyeloablative lymphodepletion, administered prior to lifileucel infusion, and interleukin-2, administered at a high dose following infusion. Adverse events (AEs) subsided rapidly within 2 weeks of lifileucel infusion, and there were no new safety concerns reported. Deaths due to adverse events of any cause occurred in 7.7% of the safety population (n = 156), and 5 deaths were attributed to treatment-related AEs, including pneumonia, arrhythmia, acute respiratory failure, and intra-abdominal hemorrhage.

These final analysis data were also presented earlier this year at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting. Overall, the data solidify lifileucel as a durable, clinically meaningful treatment option and reinforce its critical role in immune checkpoint inhibitor (ICI)-resistant advanced melanoma.

“This 5-year analysis is the longest follow-up of lifileucel in patients with ICI-resistant melanoma,” wrote study authors Medina et al in the Journal of Clinical Oncology publication.¹ “Lifileucel provides an optimal response when administered soon after treatment failure with anti–PD-1/PD-L1 or BRAF/MEK inhibitors.”

About the C-144-01 Trial

The phase 2 C-144-01 trial was a single-arm, open-label, multicenter, multicohort study evaluating the efficacy and safety of lifileucel, a tumor-derived T cell immunotherapy, as treatment for adult patients with unresectable or metastatic melanoma.²

Patients were included if they had progressed following at least 1 prior systemic therapy including a PD-1–blocking antibody, and if harboring a BRAF V600 mutation, a BRAF inhibitor with or without a MEK inhibitor. Other inclusion criteria included, but were not limited to, having at least 1 measurable target lesion and at least 1 resectable lesion of a minimum of 1.5 cm in diameter to generate TIL. Patients were enrolled into 1 of 4 experimental cohorts, with cohort 4 being the pivotal registrational cohort.

An initial data readout from the trial in June 2020 showed promising early efficacy with a 32.4% ORR at a median follow-up of 5.3 months in cohort 4 (n = 68). After more than 28 months of follow-up, the ORR was reported as 36.4%.

At the 2023 European Society for Medical Oncology (ESMO) Congress, an analysis pooling patients from cohorts 2 and 4 revealed an ORR of 31.5% (95% CI, 21.1%–43.4%), with the median DOR not yet reached.

Lifileucel’s Regulatory Pathway

The promising ORR and DOR data from the C-144-01 study ultimately culminated in the FDA’s accelerated approval of lifileucel for treatment of adult patients with unresectable or metastatic melanoma previously treated with an anti–PD-1 or BRAF/MEK inhibitor on February 16, 2024.³ This approval marked the first FDA approval of a T-cell therapy for a solid tumor cancer.⁴

This decision arrived after several additional months of anticipation during lifileucel’s biologics license application (BLA) process, which was granted FDA priority review. Rolling submission of lifileucel’s BLA was initiated in August 2022; in November 2022, the FDA delayed the BLA until the start of 2023, requesting additional data on the agent. Following BLA acceptance in May 2023 and a target action date initially set for November 2023, the FDA extended its review to February 2024 due to resource constraints on the agency’s end at the time for expedited review.

Lifileucel was also previously granted fast track, regenerative medicine advanced therapy, and orphan drug designations by the FDA.^3,5

With accelerated approval, the phase 3 TILVANCE-301 study (NCT05727904) is now underway to confirm clinical benefit of lifileucel in a randomized setting to progress toward full FDA approval.⁶ The study is evaluating the efficacy and safety of lifileucel combined with pembrolizumab (Keytruda) vs pembrolizumab alone in the approved indication and aims to enroll approximately 670 patients across 72 global sites.

REFERENCES

1. Medina T, Chesney JA, Kluger HM, et al. Long-term efficacy and safety of lifileucel tumor-infiltrating lymphocyte cell therapy in patients with advanced melanoma: A 5-year analysis of the C-144-01 study. J Clin Oncol. 2025;43(33):3565-3572. doi:10.1200/jco-25-00765

2. Study of lifileucel (LN-144), autologous tumor infiltrating lymphocytes, in the treatment of patients with metastatic melanoma (LN-144). ClinicalTrials.gov. Updated November 26, 2024. Accessed November 24, 2025. https://www.clinicaltrials.gov/study/NCT02360579

3. FDA grants accelerated approval to lifileucel for unresectable or metastatic melanoma. US FDA. February 17, 2024. Accessed November 25, 2025. https://tinyurl.com/mr2j54ck

4. Iovance’s AMTAGVI™ (lifileucel) receives U.S. FDA accelerated approval for advanced melanoma. News release. Iovance Biotherapeutics. February 16, 2024. Accessed November 25, 2025. https://tinyurl.com/3y96yjfz

5. U.S. Food and Drug Administration updates Prescription Drug User Fee Act (PDUFA) action date for lifileucel for the treatment of advanced melanoma. News release. Iovance Biotherapeutics. September 14, 2023. Accessed November 25, 2025. https://tinyurl.com/ywbanydf

6. Study to investigate lifileucel regimen plus pembrolizumab compared with pembrolizumab alone in participants with untreated advanced melanoma. ClinicalTrials.gov. Updated July 8, 2025. Accessed November 25, 2025. https://www.clinicaltrials.gov/study/NCT05727904