TY - JOUR
T1 - Lifileucel, a Tumor-Infiltrating Lymphocyte Therapy, in Metastatic Melanoma
AU - Sarnaik, Amod A.
AU - Hamid, Omid
AU - Khushalani, Nikhil I.
AU - Lewis, Karl D.
AU - Medina, Theresa
AU - Kluger, Harriet M.
AU - Thomas, Sajeve S.
AU - Domingo-Musibay, Evidio
AU - Pavlick, Anna C.
AU - Whitman, Eric D.
AU - Martin-Algarra, Salvador
AU - Corrie, Pippa
AU - Curti, Brendan D.
AU - Oláh, Judit
AU - Lutzky, Jose
AU - Weber, Jeffrey S.
AU - Larkin, James M.G.
AU - Shi, Wen
AU - Takamura, Toshimi
AU - Jagasia, Madan
AU - Qin, Harry
AU - Wu, Xiao
AU - Chartier, Cecile
AU - Graf Finckenstein, Friedrich
AU - Fardis, Maria
AU - Kirkwood, John M.
AU - Chesney, Jason A.
N1 - 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.
PY - 2021/8/20
Y1 - 2021/8/20
N2 - 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.
AB - 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.
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U2 - 10.1200/JCO.21.00612
DO - 10.1200/JCO.21.00612
M3 - Article
C2 - 33979178
AN - SCOPUS:85114521992
SN - 0732-183X
VL - 39
SP - 2656
EP - 2666
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 24
ER -
