Iovance Biotherapeutics’ Lifileucel Produces Durable Responses in 5-Year Analysis of Advanced Melanoma Data

Iovance Biotherapeutics’ lifileucel (marketed as Amtagvi), an FDA-approved autologous tumor infiltrating lymphocyte (TIL) therapy, has produced durable responses in a 5-year analysis of data from patients with advanced melanoma treated the phase 2 C-144-01 clinical trial (NCT02360579).^1,2 The analysis is being presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting, held May 30 to June 3, in Chicago, Illinois, and was simultaneously published in The Journal of Clinical Oncology.

The analysis included 153 patients with a median follow-up of 57.8 months. All of these patients completed or discontinued participation in C-144-01 and 28 of the 153 (18.3%) completed the 5-year study follow-up. The complete response rate was 5.9% and the partial response rate was 25.5%, thus yielding an objective response rate of 31.4%. Furthermore, the patients achieved a median duration of response of 36.5 months (95% confidence interval [CI]: 8.3–not reached). A sustained response at completion of the 5-year assessment was seen in 31.3% of the patients whose disease responded. The time to best response ranged from 1.3 to 30.4 months (median, 1.5 months). The medianoverall survival (OS) was reported as 13.9 months (95% CI: 10.6–17.8) and the 5-year OS rate was determined to be 19.7% (95% CI: 13.3–27.0). Iovance pointed out that for patients who responded, survival outcomes were consistent without regard to the time that their response began.

With regard to safety, first author Theresa Medina, MD, a medical oncologist at the University of Colorado Cancer Center on the Anschutz Medical Campus, and colleagues noted that no new safety signals appeared in the extended follow-up and that the treatment-emergent adverse events (AEs) that occurred were consistent with the known safety profile of nonmyeloablative lymphodepletion and interleukin-2. Iovance added that AE incidence dropped in a rapid manner in the 2 weeks following administration of lifileucel.

“This 5-year analysis of the C-144-01 trial is the longest follow-up of the largest group of patients with melanoma treated with TILs in a single study,” Medina and colleagues wrote in the ASCO abstract.¹ “This study illustrates lifileucel’s continued durability of response and survival benefit up to 5 years after a single administration without any long-term safety concerns.”

The age of the 153 patients ranged from 20 to 79 years (median, 56) and the group was composed of 54% men. All of the patients had been previously treated with antiPD-1/PD-L1 therapy, and 55% of the patients were primary refractory to that therapy. All patients in the trial also had an Eastern Cooperative Oncology Group Performance Status of 0 or 1. The number of prior lines of therapy received by the patients ranged from 1 to 9 (median, 3).

“Amtagvi has demonstrated long-term benefit and meaningful OS in a difficult-to-treat melanoma patient population resistant to immune checkpoint inhibitor therapy,” Medina said in a June 2, 2025, press release.² “Five years following one-time Amtagvi treatment, responses persisted or deepened during an extended treatment-free interval for some patients. Amtagvi offers a new standard of care for the advanced melanoma community and sets a new bar for one-time cell therapies with curative intent in solid tumors.”

Lifileucel was granted accelerated approval by the FDA on February 16, 2024, for the treatment of adult patients with unresectable or metastatic melanoma previously treated with a PD-1 blocking antibody, or treated with a BRAF inhibitor with or without an MEK inhibitor in the instance that the patient is BRAF V600 positive.^3,4 It is the first cellular therapy to have received this indication.

REFERENCES
1. Medina T. Lifileucel in patients with advanced melanoma: 5-year outcomes of the C-144-01 study. Presented at the 2025 ASCO Annual Meeting, held May 30 to June 3, in Chicago, Illinois. Abstract #9515
2. The Journal of Clinical Oncology publishes five-year analysis of Amtagvi® (lifileucel) in patients with advanced melanoma. News release. Iovance Biotherapeutics, Inc. June 2, 2025. Accessed June 3, 2025. https://ir.iovance.com/news-releases/news-release-details/journal-clinical-oncology-publishes-five-year-analysis-amtagvir
3. FDA grants accelerated approval to lifileucel for unresectable or metastatic melanoma. News release. FDA. February 16, 2024. Accessed June 3, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-lifileucel-unresectable-or-metastatic-melanoma
4. FDA Approves First Cellular Therapy to Treat Patients with Unresectable or Metastatic Melanoma. News release. FDA. February 16, 2024. Accessed June 3, 2025. https://www.fda.gov/news-events/press-announcements/fda-approves-first-cellular-therapy-treat-patients-unresectable-or-metastatic-melanoma