Lifileucel Shows Durable 5-Year Benefit in Advanced Melanoma Resistant to Immune Checkpoint Inhibitors

The durability of response observed with lifileucel (Amtagvi) at 5 years of follow-up highlights its utility as a second-line therapy for patients with advanced melanoma after an immune checkpoint inhibitor–based regimen, according to Theresa Medina, MD.

In data presented at the 2025 ASCO Annual Meeting, final results from the phase 2 C-144-01 trial (NCT02360579) represented the longest prospective follow-up of any therapy in the second-line or later setting for this patient population, Medina said. The data showed that one-time lifileucel therapy produced durable responses, with a 5-year overall survival rate of 19.7%.1 Notably, after the cellular therapy was previously shown to generate an overall response rate (ORR) of 31.4%, 31.3% of those responders remained in ongoing remission at the 5-year assessment.. Some patients experienced deepening responses over time, with partial responses converting to complete responses years after treatment. The safety profile also remained favorable, with no new or late-onset adverse effects (AEs) attributed to lifileucel.

“Lifileucel is something that we should be considering and recommending for our patients right away after they have been exposed to immune checkpoint inhibitor therapy,” Medina noted.

In an interview with OncLive®, Medina detailed the key findings from the 5-year update for lifileucel and expanded on where it fits in the melanoma treatment paradigm. In February 2024, the FDA granted accelerated approval to lifileucel for the treatment of adult patients with unresectable or metastatic melanoma previously treated with a PD-1 antibody, and if BRAF V600 positive, a BRAF inhibitor with or without a MEK inhibitor.2

OncLive: How would you describe the significance of this therapy in the treatment landscape for melanoma?

[Lifileucel] is a breakthrough therapy [and] the first cellular therapy [approved] in solid tumors. Therefore, it's very important to look at the durability of responses to see if it’s comparable to our approach to treating first-line metastatic melanoma with immune checkpoint inhibitor–based therapy.

What data had been presented before this most recent update?

We have [previously presented] earlier outcomes looking at overall response rate and durability of responses. The overall response rate in this highly refractory patient population [was previously] 31.4%, and in this 5-year update, we're getting more long-term results to evaluate the durability of responses. It's impressive that the patients who initially [responded] have ongoing responses, even between years 3 and 5, and there are also deepening responses over that time.

What were the key efficacy data presented with the 5-year update?

[In the study], 31.4% of patients [had] an initial response, and 31.3% of those patients completed the 5-year analysis and still had ongoing responses at that time. We also [saw] that there were several patients who converted from an initial stable disease or partial response to a complete response, even after a year of receiving a single infusion of lifileucel. The treatment effect was persistent and [continued] even after they were off therapy.

[These data are] exciting. [Lifileucel] is a great option for patients who either never respond to immune checkpoint inhibitor therapy or become resistant to immune checkpoint inhibitor therapy. Lifileucel is now [an] approved therapy that could be a standard therapy for patients in the second-line setting. We can see patients who have ongoing survival at 5 years as well—19.7% of patients were still alive at 5 years after treatment, which is incredible.

What did the data show regarding adverse effects (AEs) associated with lifileucel?

AEs [primarily] happened initially during the course of therapy, so most of the toxicities resolved within 2 weeks after the lifileucel infusion. These [were] particularly associated with the non-myeloablative lymphodepletion chemotherapy and high-dose interleukin-2. There were no new or late-onset AEs that we [observed] related to lifileucel.

As more data emerge, what key takeaways or calls to action would you emphasize for clinicians?

We now have the longest follow-up of any therapy in the second-line or higher setting with this therapy, which demonstrates very durable responses with a meaningful survival outcome for patients who really don't have any other treatment options.

Are there any future analyses or follow-up studies with lifileucel are most important to further define its role in melanoma treatment?

We're always interested in the expansion of combination approaches, [and] neoadjuvant outcomes are also important. For patients in this refractory setting, what other options might be available for them?

This is the final 5-year analysis of the C-144-01 trial, and from that, we now have the longest prospective data from lifileucel or any therapy [in this space]. Again, in the second-line setting, [it] demonstrates durable, deepening responses for patients, meaningful survival, and no new or late-onset adverse effects.

References

1. Medina T, Chesney JA, Kluger HM, et al. Lifileucel in patients with advanced melanoma: 5-year outcomes of the C-144-01 study. J Clin Oncol. 2025;43(16_suppl):9515-9515. doi:10.1200/jco.2025.43.16_suppl.9515
2. FDA approves first cellular therapy to treat patients with unresectable or metastatic melanoma. News release. FDA. February 16, 2024. Accessed February 16, 2024. https://www.fda.gov/news-events/press-announcements/fda-approves-first-cellular-therapy-treat-patients-unresectable-or-metastatic-melanoma