Study of Lifileucel (LN-144), Autologous Tumor Infiltrating Lymphocytes, in the Treatment of Patients With Metastatic Melanoma

NCT02360579 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: C-144-01
• Study Type: interventional
• Target: 220
• Locations: 8 countries
• Sites: 57

Brief Summary

Prospective, interventional multicenter study evaluating adoptive cell therapy (ACT) via infusion of LN-144 (autologous TIL) followed by interleukin 2 (IL-2) after a nonmyeloablative lymphodepletion (NMA LD) preconditioning regimen.

Conditions

Metastatic Melanoma

Keywords

Autologous Adoptive Cell Transfer; Autologous Adoptive Cell Therapy; Cellular Immuno-therapy; Cell Therapy; Tumor Infiltrating Lymphocytes; TIL; LN-144; IL-2; Melanoma; Lifileucel

Outcome Measures

Primary Outcomes (1)

• Disease Assessment for Objective Response Rate

  Evaluate the efficacy of LN-144 in patients with unresectable or metastatic melanoma using the objective response rate (ORR), as assessed by the investigator per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 for Cohorts 1 \& 3 and as assessed by Independent Review Committee (IRC) per RECIST Version 1.1 for Cohorts 2 \& 4

  Every 6 weeks for 6 months, then every 3 months for a maximum of 60 months

Secondary Outcomes (5)

• Disease Assessment for Duration of Response

  Every 6 weeks for 6 months, then every 3 months for a maximum of 60 months

• Disease Assessment for Disease Control Rate

  Every 6 weeks for 6 months, then every 3 months for a maximum of 60 months

• Disease Assessment for Progression-Free Survival

  Every 6 weeks for 6 months, then every 3 months for a maximum of 60 months

• Overall Survival

  Until death or up to 60 months

• Safety Profile

  Maximum 60 months

Study Arms (4)

Cohort 1

EXPERIMENTAL

Non-cryopreserved LN-144 (Gen 1 infusion product) (Closed)

Biological: Lifileucel

Cohort 2

EXPERIMENTAL

Cryopreserved lifileucel (LN-144) (Gen 2 infusion product) (Closed)

Biological: Lifileucel

Cohort 3

EXPERIMENTAL

Retreatment cohort: patients from Cohort 1, Cohort 2 or Cohort 4 may rescreen for a second TIL regimen therapy if they meet all Inclusion and Exclusion Criteria (except exclusion criterion b).

Biological: Lifileucel

Cohort 4

EXPERIMENTAL

Cryopreserved lifileucel (LN-144) (Gen 2 infusion product)

Biological: Lifileucel

Interventions

Lifileucel BIOLOGICAL

A tumor sample is resected from each patient and cultured ex vivo to expand the population of tumor infiltrating lymphocytes. After lymphodepletion, patients are infused with lifileucel followed by IL-2.

Also known as: LN - 144

Cohort 1; Cohort 2; Cohort 3; Cohort 4

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with unresectable or metastatic melanoma (Stage IIIc or Stage IV)
• Patients must have progressed following ≥ one prior systemic therapy including a programmed cell death protein-1 (PD-1) blocking antibody; and if proto-oncogene B-Raf (BRAF) V600 mutation-positive, a BRAF inhibitor or BRAF inhibitor in combination with mitogen-activated extracellular signal-regulated kinase (MEK) inhibitor
• At least one measurable target lesion, as defined by RECIST v1.1
• Lesions in previously irradiated areas (or other local therapy) should not be selected as target lesions, unless treatment was ≥ 3 months prior to Screening, and there has been demonstrated disease progression in that particular lesion
• At least one resectable lesion (or aggregate of lesions resected) of a minimum 1.5 cm in diameter post-resection to generate TIL; surgical removal with minimal morbidity (defined as any procedure for which expected hospitalization is ≤ 3 days)
• Patients must be ≥ 18 years of age at the time of consent. Enrollment of patients \> 70 years of age may be allowed after consultation with the Medical Monitor
• Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 and an estimated life expectancy of ≥ 3 months
• In the opinion of the Investigator, patients must be able to complete all study-required procedures
• Patients must have the following hematologic parameters:
• Absolute neutrophil count (ANC) ≥ 1000/mm3
• Hemoglobin (Hb) ≥ 9.0 g/dL
• Platelet ≥ 100,000/mm3
• Patients must have adequate organ function:
• Serum alanine transaminase (ALT)/serum glutamic-pyruvic transaminase (SGPT) and aspartate transaminase (AST)/serum glutamic-oxaloacetic transaminase (SGOT) ≤ 3 times the upper limit of normal (ULN); patients with liver metastasis ≤ 5 times ULN
• Estimated creatinine clearance (eCrCl) ≥ 40 mL/min using the Cockcroft-Gault formula

You may not qualify if:

• Patients who meet any of the following criteria are not eligible for participation in this study:
• Patients who have been shown to be BRAF mutation positive (V600), but have not received prior systemic therapy with a BRAF inhibitor alone or a BRAF inhibitor in combination with a MEK inhibitor
• Patients who have received an organ allograft or prior cell transfer therapy
• Patients with melanoma of uveal/ocular origin
• Patients who have a history of hypersensitivity to any component or excipient of LN-144 or other study drugs:
• NMA-LD preconditioning regimen (cyclophosphamide, mesna, and fludarabine)
• Antibiotics (ABX) of the aminoglycoside group (ie, streptomycin, gentamicin); except those who are skin-test negative for gentamicin hypersensitivity
• Any component of the LN-144 infusion product formulation including dimethyl sulfoxide (DMSO), human serum albumin (HSA), IL-2, and dextran-40
• Patients with symptomatic and/or untreated brain metastases (of any size and any number)
• Patients with definitively treated brain metastases may be considered for Enrollment, and must be stable for ≥ 14 days prior to beginning the NMA LD preconditioning regimen
• Patients who are on chronic systemic steroid therapy for any reason
• Patients who have active medical illness(es) that would pose increased risk for study participation, including: active systemic infections requiring systemic ABX, coagulation disorders, or other active major medical illnesses of the cardiovascular, respiratory, or immune system
• Patients who have any form of primary immunodeficiency (such as severe combined immunodeficiency disease \[SCID\] and acquired immunodeficiency syndrome \[AIDS\])
• Patients who have a left ventricular ejection fraction (LVEF) \< 45% or New York Heart Association (NYHA) functional classification \> Class 1
• Patients ≥ 60 years of age and who have a history of ischemic heart disease, chest pain, or clinically significant atrial and/or ventricular arrhythmias must have a cardiac stress test. Patients with any irreversible wall movement abnormalities are excluded

Sponsors & Collaborators

• Iovance Biotherapeutics, Inc.: lead

Study Sites (57)

University of California San Diego Moores Cancer Center

La Jolla, California, 92093, United States

Location

The Angeles Clinic and Research Institute

Los Angeles, California, 90048, United States

Location

University of California Los Angeles - David Geffen School of Medicine - Westwood Rheumatology

Los Angeles, California, 90095, United States

Location

California Pacific Medical Center

San Francisco, California, 94115, United States

Location

University of Colorado Cancer Center

Aurora, Colorado, 80049, United States

Location

Yale Cancer Center

New Haven, Connecticut, 06510, United States

Location

University of Miami

Miami, Florida, 33136, United States

Location

Mount Sinai Comprehensive Cancer Center

Miami Beach, Florida, 33140, United States

Location

University of Florida Health Cancer Center

Orlando, Florida, 32806, United States

Location

University of South Florida H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, 33612, United States

Location

Indiana University

Indianapolis, Indiana, 46202-5116, United States

Location

James Graham Brown Cancer Center

Louisville, Kentucky, 40202, United States

Location

University of Minnesota, Masonic Cancer Center

Minneapolis, Minnesota, 55455, United States

Location

Atlantic Health System

Morristown, New Jersey, 07960, United States

Location

Rutgers University

New Brunswick, New Jersey, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

New York University Langone Medical Center

New York, New York, 10016, United States

Location

Providence Cancer Center Oncology and Hematology Care Clinic

Portland, Oregon, 97213, United States

Location

Thomas Jefferson University

Philadelphia, Pennsylvania, 19701, United States

Location

University of Pittsburgh Medical Center - Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

Location

Virginia Commonwealth University

Richmond, Virginia, 23298, United States

Location

Seattle Cancer Care Alliance

Seattle, Washington, 98109, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Centre Léon Bérard

Lyon, Auvergne-Rhône-Alpes, 69008, France

Location

Centre Hospitalier Lyon Sud

Pierre-Bénite, Auvergne-Rhône-Alpes, 69495, France

Location

Hôpital Dupuytren

Limoges, Limousin, 87042, France

Location

Gustave Roussy Cancer Campus

Villejuif, Île-de-France Region, 94805, France

Location

Universitaetsklinikum Heidelberg

Heidelberg, Baden-Wurttemberg, 69120, Germany

Location

Universitaetsklinikum Tuebingen (UKT) - Suedwestdeutschen Tumorzentrum - Zentrum für Neuroonkologie

Tübingen, Baden-Wurttemberg, 72076, Germany

Location

Universitätsklinikum Erlangen

Erlangen, Bavaria, 91052, Germany

Location

Klinikum Rechts der Isar der Technischen Universität München

München, Bavaria, 81675, Germany

Location

Universitätsklinikum Carl Gustav Carus

Dresden, Saxony, Germany

Location

Universitätsklinikum Leipzig

Leipzig, Saxony, 4103, Germany

Location

Universitätsklinikum Halle

Halle, Saxony-Anhalt, 06120, Germany

Location

Universitätsklinikum Schleswig-Holstein - Campus Lübeck

Lübeck, Schleswig-Holstein, 23538, Germany

Location

Universitätsklinikum Würzburg

Würzburg, 97080, Germany

Location

Szegedi Tudomanyegyetem Szent-Györgyi Albert Klinikai Központ

Szeged, Csongrád megye, 6720, Hungary

Location

Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori

Meldola, Forli-cesena, 47014, Italy

Location

Centro di Riferimento Oncologico di Aviano

Aviano, Pordenone, 33081, Italy

Location

Istituto di Candiolo - Fondazione del Piemonte per l'Oncologia

Candiolo, Torino, 10060, Italy

Location

Istituto Europeo di Oncologia

Milan, 20141, Italy

Location

Istituto Nazionale Tumori IRCCS Fondazione Pascale

Naples, 80131, Italy

Location

Clínica Universidad de Navarra

Pamplona, Navarre, 31008, Spain

Location

Hospital Universitari Vall d'Hebrón

Barcelona, 08035, Spain

Location

Hospital Clinic de Barcelona

Barcelona, 08036, Spain

Location

Institut Català d'Oncologia

Barcelona, 08907, Spain

Location

Hospital General Universitario Gregorio Marañon

Madrid, 28007, Spain

Location

Hospital 12 de Octubre

Madrid, 28041, Spain

Location

HM Centro Integral Oncológico Clara Campal

Madrid, 28050, Spain

Location

Hospital Universitario Quirónsalud Madrid

Madrid, 28233, Spain

Location

Consorci Hospital General Universitari de València

Valencia, Spain

Location

Inselspital

Bern, 3010, Switzerland

Location

Centre Hospitalier Universitaire Vaudois Lausanne - Centre Pluridisciplinaire d'Oncologie

Lausanne, Switzerland

Location

Royal Marsden NHS Trust

London, England, SW3 6JJ, United Kingdom

Location

Beatson West of Scotland Cancer Centre

Glasgow, Scotland, G12 0YN, United Kingdom

Location

Addenbrooke's Hospital

Cambridge, CB2 0QQ, United Kingdom

Location

Sarah Cannon Research Institute London

London, W1G 6AD, United Kingdom

Location

Related Publications (4)

• Chesney J, Lewis KD, Kluger H, Hamid O, Whitman E, Thomas S, Wermke M, Cusnir M, Domingo-Musibay E, Phan GQ, Kirkwood JM, Hassel JC, Orloff M, Larkin J, Weber J, Furness AJS, Khushalani NI, Medina T, Egger ME, Graf Finckenstein F, Jagasia M, Hari P, Sulur G, Shi W, Wu X, Sarnaik A. Efficacy and safety of lifileucel, a one-time autologous tumor-infiltrating lymphocyte (TIL) cell therapy, in patients with advanced melanoma after progression on immune checkpoint inhibitors and targeted therapies: pooled analysis of consecutive cohorts of the C-144-01 study. J Immunother Cancer. 2022 Dec;10(12):e005755. doi: 10.1136/jitc-2022-005755.

  PMID: 36600653 BACKGROUND

• Medina T, Chesney JA, Kluger HM, Hamid O, Whitman ED, Cusnir M, Thomas SS, Wermke M, Domingo-Musibay E, Phan GQ, Kirkwood JM, Larkin J, Weber J, Graf Finckenstein F, Chou J, Gastman B, Wu X, Fiaz R, Sarnaik AA; C-144-01 Investigators. 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 Nov 20;43(33):3565-3572. doi: 10.1200/JCO-25-00765. Epub 2025 Jun 2.

  PMID: 40454684 BACKGROUND

• Kluger H, Grigoleit GU, Thomas S, Domingo-Musibay E, Chesney JA, Sanmamed MF, Medina T, Ziemer M, Whitman E, Finckenstein FG, Gastman B, Chou J, Wu X, Sulur G, Fiaz R, Qi R, Sarnaik AA. Lifileucel tumor-infiltrating lymphocyte cell therapy in patients with unresectable or metastatic mucosal melanoma after disease progression on immune checkpoint inhibitors. Cancer Commun (Lond). 2025 Oct;45(10):1229-1234. doi: 10.1002/cac2.70050. Epub 2025 Jul 22. No abstract available.

  PMID: 40693376 BACKGROUND

• Sarnaik AA, Hamid O, Khushalani NI, Lewis KD, Medina T, Kluger HM, Thomas SS, Domingo-Musibay E, Pavlick AC, Whitman ED, Martin-Algarra S, Corrie P, Curti BD, Olah J, Lutzky J, Weber JS, Larkin JMG, Shi W, Takamura T, Jagasia M, Qin H, Wu X, Chartier C, Graf Finckenstein F, Fardis M, Kirkwood JM, Chesney JA. Lifileucel, a Tumor-Infiltrating Lymphocyte Therapy, in Metastatic Melanoma. J Clin Oncol. 2021 Aug 20;39(24):2656-2666. doi: 10.1200/JCO.21.00612. Epub 2021 May 12.

  PMID: 33979178 DERIVED

MeSH Terms

Conditions

Melanoma

Interventions

lifileucel

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Results Point of Contact

• Title: Rana Fiaz, Executive Medical Director
• Organization: Iovance Biotherapeutics

rana.fiaz@iovance.com

661-645-3572

Study Officials

• Iovance Biotherapeutics Medical Monitor

  Iovance Biotherapeutics, Inc.

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 3, 2015
• First Posted: February 10, 2015
• Study Start: September 24, 2015
• Primary Completion: October 24, 2024
• Study Completion: October 24, 2024
• Last Updated: March 25, 2026
• Results First Posted: December 9, 2025

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

CH (2); ES (9); DE (9); FR (4); IT (5); GB (4); US (23); HU (1)