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

A Phase 2, Multicenter Study to Assess the Efficacy and Safety of Autologous Tumor Infiltrating Lymphocytes (LN-144) for Treatment of Patients With Metastatic Melanoma

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.

Study Overview

• Status: Completed
• Conditions: Metastatic Melanoma
• Intervention / Treatment: Biological: Lifileucel

Detailed Description

Lifileucel is an autologous adoptive cell transfer therapy that utilizes a TIL manufacturing process, as originally developed by the NCI, for the treatment of patients with metastatic melanoma. The adoptive cell transfer therapy used in this study involves patients receiving a lymphocyte depleting preconditioning regimen, prior to infusion of autologous TIL, followed by the administration of a regimen of IL-2.

• Study Type: Interventional
• Enrollment (Actual): 220
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Auvergne-Rhône-Alpes
    • Lyon, Auvergne-Rhône-Alpes, France, 69008
      • Centre Leon Berard
    • Pierre-Bénite, Auvergne-Rhône-Alpes, France, 69495
      • Centre Hospitalier Lyon Sud
  • Limousin
    • Limoges, Limousin, France, 87042
      • Hopital Dupuytren
  • Île-de-France Region
    • Villejuif, Île-de-France Region, France, 94805
      • Gustave Roussy Cancer Campus
• Germany
  • Würzburg, Germany, 97080
    • Universitätsklinikum Würzburg
  • Baden-Wurttemberg
    • Heidelberg, Baden-Wurttemberg, Germany, 69120
      • UniversitaetsKlinikum Heidelberg
    • Tübingen, Baden-Wurttemberg, Germany, 72076
      • Universitaetsklinikum Tuebingen (UKT) - Suedwestdeutschen Tumorzentrum - Zentrum für Neuroonkologie
  • Bavaria
    • Erlangen, Bavaria, Germany, 91052
      • Universitätsklinikum Erlangen
    • München, Bavaria, Germany, 81675
      • Klinikum rechts der Isar der Technischen Universität München
  • Saxony
    • Dresden, Saxony, Germany
      • Universitätsklinikum Carl Gustav Carus
    • Leipzig, Saxony, Germany, 4103
      • Universitatsklinikum Leipzig
  • Saxony-Anhalt
    • Halle, Saxony-Anhalt, Germany, 06120
      • Universitätsklinikum Halle
  • Schleswig-Holstein
    • Lübeck, Schleswig-Holstein, Germany, 23538
      • Universitatsklinikum Schleswig-Holstein - Campus Lubeck
• Hungary
  • Csongrád megye
    • Szeged, Csongrád megye, Hungary, 6720
      • Szegedi Tudományegyetem Szent-Györgyi Albert Klinikai Központ
• Italy
  • Milan, Italy, 20141
    • Istituto Europeo di Oncologia
  • Naples, Italy, 80131
    • Istituto Nazionale Tumori IRCCS Fondazione Pascale
  • Forli-cesena
    • Meldola, Forli-cesena, Italy, 47014
      • Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori
  • Pordenone
    • Aviano, Pordenone, Italy, 33081
      • Centro di Riferimento Oncologico di Aviano
  • Torino
    • Candiolo, Torino, Italy, 10060
      • Istituto di Candiolo - Fondazione del Piemonte per l'Oncologia
• Spain
  • Barcelona, Spain, 08036
    • Hospital Clinic De Barcelona
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d'Hebron
  • Barcelona, Spain, 08907
    • Institut Catala d'Oncologia
  • Madrid, Spain, 28007
    • Hospital General Universitario Gregorio Marañon
  • Madrid, Spain, 28041
    • Hospital 12 de Octubre
  • Madrid, Spain, 28050
    • HM Centro Integral Oncológico Clara Campal
  • Madrid, Spain, 28233
    • Hospital Universitario Quironsalud Madrid
  • Valencia, Spain
    • Consorci Hospital General Universitari de València
  • Navarre
    • Pamplona, Navarre, Spain, 31008
      • Clinica Universidad de Navarra
• Switzerland
  • Bern, Switzerland, 3010
    • Inselspital
  • Lausanne, Switzerland
    • Centre Hospitalier Universitaire Vaudois Lausanne - Centre Pluridisciplinaire d'Oncologie
• United Kingdom
  • Cambridge, United Kingdom, CB2 0QQ
    • Addenbrooke's Hospital
  • London, United Kingdom, W1G 6AD
    • Sarah Cannon Research Institute London
  • England
    • London, England, United Kingdom, SW3 6JJ
      • Royal Marsden NHS Trust
  • Scotland
    • Glasgow, Scotland, United Kingdom, G12 0YN
      • Beatson West of Scotland Cancer Centre
• United States
  • California
    • La Jolla, California, United States, 92093
      • University of California San Diego Moores Cancer Center
    • Los Angeles, California, United States, 90048
      • The Angeles Clinic and Research Institute
    • Los Angeles, California, United States, 90095
      • University of California Los Angeles - David Geffen School of Medicine - Westwood Rheumatology
    • San Francisco, California, United States, 94115
      • California Pacific Medical Center
  • Colorado
    • Aurora, Colorado, United States, 80049
      • University of Colorado Cancer Center
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Yale Cancer Center
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami
    • Miami Beach, Florida, United States, 33140
      • Mount Sinai Comprehensive Cancer Center
    • Orlando, Florida, United States, 32806
      • University of Florida Health Cancer Center
    • Tampa, Florida, United States, 33612
      • University of South Florida H. Lee Moffitt Cancer Center and Research Institute
  • Indiana
    • Indianapolis, Indiana, United States, 46202-5116
      • Indiana University
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • James Graham Brown Cancer Center
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota, Masonic Cancer Center
  • New Jersey
    • Morristown, New Jersey, United States, 07960
      • Atlantic Health System
    • New Brunswick, New Jersey, United States
      • Rutgers University
  • New York
    • Buffalo, New York, United States, 14263
      • Roswell Park Cancer Institute
    • New York, New York, United States, 10016
      • New York University Langone Medical Center
  • Oregon
    • Portland, Oregon, United States, 97213
      • Providence Cancer Center Oncology and Hematology Care Clinic
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19701
      • Thomas Jefferson University
    • Pittsburgh, Pennsylvania, United States, 15232
      • University of Pittsburgh Medical Center - Hillman Cancer Center
  • Virginia
    • Richmond, Virginia, United States, 23298
      • Virginia Commonwealth University
  • Washington
    • Seattle, Washington, United States, 98109
      • Seattle Cancer Care Alliance
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Patients must meet all of the following inclusion criteria to be eligible for participation in the study:

Criteria for Inclusion:

1. Patients with unresectable or metastatic melanoma (Stage IIIc or Stage IV)
2. 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

3. 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
4. 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)
5. 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
6. Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 and an estimated life expectancy of ≥ 3 months
7. In the opinion of the Investigator, patients must be able to complete all study-required procedures

8. Patients must have the following hematologic parameters:

   • Absolute neutrophil count (ANC) ≥ 1000/mm3
   • Hemoglobin (Hb) ≥ 9.0 g/dL
   • Platelet ≥ 100,000/mm3

9. 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
   • Total bilirubin ≤ 2 mg/dL
   • Patients with Gilbert's syndrome must have a total bilirubin ≤ 3 mg/dL

10. Patients must have recovered from all prior therapy-related adverse events (AEs) to ≤ Grade 1 (per Common Terminology Criteria for Adverse Events [CTCAE] v4.03), except for alopecia or vitiligo, prior to Enrollment (tumor resection)

    • Patients with documented ≥ Grade 2 diarrhea or colitis as a result of previous treatment with immune checkpoint inhibitor(s) must have been asymptomatic for at least 6 months and/or had a normal colonoscopy post-immune checkpoint inhibitor treatment, by visual assessment, prior to tumor resection

11. Patients must have a washout period ≥ 28 days from prior anticancer therapy(ies) to the start of the planned NMA-LD preconditioning regimen:

    • Targeted therapy: MEK/BRAF or other targeted agent
    • Chemotherapy
    • Immunotherapy: anti-cytotoxic T lymphocyte-associated antigen 4 (CTLA-4)/anti-PD-1, other monoclonal antibody (mAb), or vaccine
    • Palliative radiation therapy is permitted so long as it does not involve lesions being selected for TIL, or as target or non-target lesions. Washout is not required if all related toxicities have resolved to ≤ Grade 1 as per CTCAE v4.03

12. Patients of childbearing potential or their partners of childbearing potential must be willing to take the appropriate precaution to avoid pregnancy or fathering a child for the duration of the study and practice an approved, highly effective method of birth control during treatment and for 12 months after receiving the last protocol-related therapy

    • Approved methods of birth control are as follows:
    • Combined (estrogen and progesterone containing) hormonal birth control associated with inhibition of ovulation: oral, intravaginal, transdermal
    • Progesterone-only hormonal birth control associated with inhibition of ovulation: oral, injectable, implantable
    • Intrauterine device (IUD)
    • Intrauterine hormone-releasing system (IUS)
    • Bilateral tubal occlusion
    • Vasectomized partner
    • True sexual abstinence when this is in line with the preferred and usual lifestyle of the patient. Periodic abstinence (eg, calendar ovulation, symptothermal, post-ovulation methods) is not acceptable
13. Patients (or legally authorized representative) must have the ability to understand the requirements of the study, have provided written informed consent as evidenced by signature on an ICF approved by an Institutional Review Board/Independent Ethics Committee (IRB/IEC), and agree to abide by the study restrictions and return to the site for the required assessments, including the OS Follow-up Period
14. Patients have provided written authorization for use and disclosure of protected health information

Criteria for Exclusion:

Patients who meet any of the following criteria are not eligible for participation in this study:

1. 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
2. Patients who have received an organ allograft or prior cell transfer therapy
3. Patients with melanoma of uveal/ocular origin

4. 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

5. 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
6. Patients who are on chronic systemic steroid therapy for any reason
7. 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
8. Patients who have any form of primary immunodeficiency (such as severe combined immunodeficiency disease [SCID] and acquired immunodeficiency syndrome [AIDS])

9. 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
10. Patients who have a documented forced expiratory volume in 1 second (FEV1) of ≤ 60%
11. Patients who have had another primary malignancy within the previous 3 years (with the exception of carcinoma in situ of the breast, cervix, or bladder; localized prostate cancer; and non-melanoma skin cancer that has been adequately treated)
12. Patients who have received a live or attenuated vaccine within 28 days of beginning the NMA-LD preconditioning regimen
13. Patients who are pregnant or breastfeeding
14. Patients whose cancer requires immediate attention or who would otherwise suffer a disadvantage by participating in this trial

15. Patients protected by the following constraints:

    • Hospitalized persons without consent or persons deprived of liberty because of a judiciary or administrative decision
    • Adult persons with a legal protection measure or persons who cannot express their consent
    • Patients in emergency situations who cannot consent to participate in the trial

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 2; Cryopreserved lifileucel (LN-144) (Gen 2 infusion product) (Closed)	Biological: Lifileucel; 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.; Other Names: LN - 144
Experimental: Cohort 3; 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; 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.; Other Names: LN - 144
Experimental: Cohort 4; Cryopreserved lifileucel (LN-144) (Gen 2 infusion product)	Biological: Lifileucel; 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.; Other Names: LN - 144
Experimental: Cohort 1; Non-cryopreserved LN-144 (Gen 1 infusion product) (Closed)	Biological: Lifileucel; 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.; Other Names: LN - 144

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease Assessment for Duration of Response	Evaluate the efficacy endpoints of duration of response (DOR) by the IRC for Cohorts 2 & 4 and by the investigator for Cohort 1 per RECIST v1.1	Every 6 weeks for 6 months, then every 3 months for a maximum of 60 months
Disease Assessment for Disease Control Rate	Evaluate the efficacy endpoints of disease control rate (DCR) by the IRC for Cohorts 2 & 4 and by the investigator for Cohort 1 per RECIST v1.1	Every 6 weeks for 6 months, then every 3 months for a maximum of 60 months
Disease Assessment for Progression-Free Survival	Evaluate the efficacy endpoints of Progression-Free Survival by the IRC for Cohorts 2 & 4 and by the investigator for Cohort 1 per RECIST v1.1	Every 6 weeks for 6 months, then every 3 months for a maximum of 60 months
Overall Survival	Evaluate overall survival (OS)	Until death or up to 60 months
Safety Profile	Incidence, seriousness, relationship to study treatment, and characteristics of treatment-emergent adverse events	Maximum 60 months

Collaborators and Investigators

• Sponsor: Iovance Biotherapeutics, Inc.
• Investigators: Study Chair: Iovance Biotherapeutics Medical Monitor, Iovance Biotherapeutics, Inc.

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): September 24, 2015
• Primary Completion (Actual): October 24, 2024
• Study Completion (Actual): October 24, 2024

Study Registration Dates

• First Submitted: February 3, 2015
• First Submitted That Met QC Criteria: February 9, 2015
• First Posted (Estimated): February 10, 2015

Study Record Updates

• Last Update Posted (Actual): March 25, 2026
• Last Update Submitted That Met QC Criteria: March 5, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Cell Therapy; Melanoma; Tumor Infiltrating Lymphocytes; IL-2; TIL; Autologous Adoptive Cell Transfer; Autologous Adoptive Cell Therapy; Cellular Immuno-therapy; LN-144; Lifileucel
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Skin Diseases; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Skin Neoplasms; Skin and Connective Tissue Diseases; Melanoma; lifileucel
• Other Study ID Numbers: C-144-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No