Lifileucel, a Tumor-Infiltrating Lymphocyte Therapy, in Metastatic Melanoma

Amod A. Sarnaik, Omid Hamid, Nikhil I. Khushalani, Karl D. Lewis, Theresa Medina, Harriet M. Kluger, Sajeve S. Thomas, Evidio Domingo-Musibay, Anna C. Pavlick, Eric D. Whitman, Salvador Martin-Algarra, Pippa Corrie, Brendan D. Curti, Judit Oláh, Jose Lutzky, Jeffrey S. Weber, James M.G. Larkin, Wen Shi, Toshimi Takamura, Madan JagasiaHarry Qin, Xiao Wu, Cecile Chartier, Friedrich Graf Finckenstein, Maria Fardis, John M. Kirkwood, Jason A. Chesney

Research output: Contribution to journalArticlepeer-review

74 Scopus citations


PURPOSE Effective treatment options are limited for patients with advanced (metastatic or unresectable) melanoma who progress after immune checkpoint inhibitors and targeted therapies. Adoptive cell therapy using tumor-infiltrating lymphocytes has demonstrated efficacy in advanced melanoma. Lifileucel is an autologous, centrally manufactured tumor-infiltrating lymphocyte product. METHODS We conducted a phase II open-label, single-arm, multicenter study in patients with advanced melanoma who had been previously treated with checkpoint inhibitor(s) and BRAF 6 MEK targeted agents. Lifileucel was produced from harvested tumor specimens in central Good Manufacturing Practice facilities using a streamlined 22-day process. Patients received a nonmyeloablative lymphodepletion regimen, a single infusion of lifileucel, and up to six doses of high-dose interleukin-2. The primary end point was investigator-assessed objective response rate (ORR) per RECIST, version 1.1. RESULTS Sixty-six patients received a mean of 3.3 prior therapies (anti–programmed death 1 [PD-1] or programmed death ligand 1 [PD-L1]: 100%; anticytotoxic T-lymphocyte-associated protein-4: 80%; BRAF 6 MEK inhibitor: 23%). The ORR was 36% (95% CI, 25 to 49), with two complete responses and 22 partial responses. Disease control rate was 80% (95% CI, 69 to 89). Median duration of response was not reached after 18.7-month median study follow-up (range, 0.2-34.1 months). In the primary refractory to anti–PD-1 or PD-L1 therapy subset, the ORR and disease control rate were 41% (95% CI, 26 to 57) and 81% (95% CI, 66 to 91), respectively. Safety profile was consistent with known adverse events associated with nonmyeloablative lymphodepletion and interleukin-2. CONCLUSION Lifileucel demonstrated durable responses and addresses a major unmet need in patients with metastatic melanoma with limited treatment options after approved therapy, including the primary refractory to anti–PD-1 or PD-L1 therapy subset.

Original languageEnglish (US)
Pages (from-to)2656-2666
Number of pages11
JournalJournal of Clinical Oncology
Issue number24
StatePublished - Aug 20 2021

Bibliographical note

Funding Information:
Supported by Iovance Biotherapeutics Inc. NIH grant that was funded during the clinical trial 5K23CA178083-03, A.A.S.

Funding Information:
Iovance Biotherapeutics sponsored the C-144-01 trial, provided the trial drugs, and collaborated with the authors on the trial design and on the collection, analysis, and interpretation of the data. Medical writing support, funded by Iovance Biotherapeutics (with specific direction from authors), was provided by Swati Ghatpande, PhD, of Second City Science (Vaniam Group LLC).

Publisher Copyright:
© 2021 by American Society of Clinical Oncology.


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