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

NCT ID: NCT02360579

Last Updated: 2025-12-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 220 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-09-24
• Study Completion Date: 2024-10-24

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.

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.

Conditions

Metastatic Melanoma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cohort 1

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

Group Type: EXPERIMENTAL

Lifileucel

Intervention Type: 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.

Cohort 2

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

Group Type: EXPERIMENTAL

Lifileucel

Intervention Type: 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.

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).

Group Type: EXPERIMENTAL

Lifileucel

Intervention Type: 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.

Cohort 4

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

Group Type: EXPERIMENTAL

Lifileucel

Intervention Type: 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.

Interventions

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.

Intervention Type: BIOLOGICAL

Other Intervention Names

LN - 144

Eligibility Criteria

Inclusion Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Iovance Biotherapeutics, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Iovance Biotherapeutics Medical Monitor

Role: STUDY_CHAIR

Iovance Biotherapeutics, Inc.

Locations

University of California San Diego Moores Cancer Center

La Jolla, California, United States

The Angeles Clinic and Research Institute

Los Angeles, California, United States

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

Los Angeles, California, United States

California Pacific Medical Center

San Francisco, California, United States

University of Colorado Cancer Center

Aurora, Colorado, United States

Yale Cancer Center

New Haven, Connecticut, United States

University of Miami

Miami, Florida, United States

Mount Sinai Comprehensive Cancer Center

Miami Beach, Florida, United States

University of Florida Health Cancer Center

Orlando, Florida, United States

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

Tampa, Florida, United States

Indiana University

Indianapolis, Indiana, United States

James Graham Brown Cancer Center

Louisville, Kentucky, United States

University of Minnesota, Masonic Cancer Center

Minneapolis, Minnesota, United States

Atlantic Health System

Morristown, New Jersey, United States

Rutgers University

New Brunswick, New Jersey, United States

Roswell Park Cancer Institute

Buffalo, New York, United States

New York University Langone Medical Center

New York, New York, United States

Providence Cancer Center Oncology and Hematology Care Clinic

Portland, Oregon, United States

Thomas Jefferson University

Philadelphia, Pennsylvania, United States

University of Pittsburgh Medical Center - Hillman Cancer Center

Pittsburgh, Pennsylvania, United States

Virginia Commonwealth University

Richmond, Virginia, United States

Seattle Cancer Care Alliance

Seattle, Washington, United States

Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Centre Léon Bérard

Lyon, Auvergne-Rhône-Alpes, France

Centre Hospitalier Lyon Sud

Pierre-Bénite, Auvergne-Rhône-Alpes, France

Hôpital Dupuytren

Limoges, Limousin, France

Gustave Roussy Cancer Campus

Villejuif, Île-de-France Region, France

Universitaetsklinikum Heidelberg

Heidelberg, Baden-Wurttemberg, Germany

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

Tübingen, Baden-Wurttemberg, Germany

Universitätsklinikum Erlangen

Erlangen, Bavaria, Germany

Klinikum Rechts der Isar der Technischen Universität München

München, Bavaria, Germany

Universitätsklinikum Carl Gustav Carus

Dresden, Saxony, Germany

Universitätsklinikum Leipzig

Leipzig, Saxony, Germany

Universitätsklinikum Halle

Halle, Saxony-Anhalt, Germany

Universitätsklinikum Schleswig-Holstein - Campus Lübeck

Lübeck, Schleswig-Holstein, Germany

Universitätsklinikum Würzburg

Würzburg, , Germany

Szegedi Tudomanyegyetem Szent-Györgyi Albert Klinikai Központ

Szeged, Csongrád megye, Hungary

Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori

Meldola, Forli-cesena, Italy

Centro di Riferimento Oncologico di Aviano

Aviano, Pordenone, Italy

Istituto di Candiolo - Fondazione del Piemonte per l'Oncologia

Candiolo, Torino, Italy

Istituto Europeo di Oncologia

Milan, , Italy

Istituto Nazionale Tumori IRCCS Fondazione Pascale

Napoli, , Italy

Clínica Universidad de Navarra

Pamplona, Navarre, Spain

Hospital Universitari Vall d'Hebrón

Barcelona, , Spain

Hospital Clinic de Barcelona

Barcelona, , Spain

Institut Català d'Oncologia

Barcelona, , Spain

Hospital General Universitario Gregorio Marañon

Madrid, , Spain

Hospital 12 de Octubre

Madrid, , Spain

HM Centro Integral Oncológico Clara Campal

Madrid, , Spain

Hospital Universitario Quirónsalud Madrid

Madrid, , Spain

Consorci Hospital General Universitari de València

Valencia, , Spain

Inselspital

Bern, , Switzerland

Centre Hospitalier Universitaire Vaudois Lausanne - Centre Pluridisciplinaire d'Oncologie

Lausanne, , Switzerland

Royal Marsden NHS Trust

London, England, United Kingdom

Beatson West of Scotland Cancer Centre

Glasgow, Scotland, United Kingdom

Addenbrooke's Hospital

Cambridge, , United Kingdom

Sarah Cannon Research Institute London

London, , United Kingdom

Countries

United States; France; Germany; Hungary; Italy; Spain; Switzerland; United Kingdom

References

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.

Reference Type: BACKGROUND

PMID: 36600653 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 40454684 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 40693376 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 33979178 (View on PubMed)

Provided Documents

Document Type: Study Protocol: Protocol V9.0

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Document Type: Study Protocol: Protocol V8.0

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Document Type: Study Protocol: Protocol V3.0

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Document Type: Study Protocol: Protocol V4.0

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Document Type: Study Protocol: Protocol V5.0 (Incorporating Amendments 1-4)

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Document Type: Study Protocol: Protocol V7.0_(Incorporating Amendments 1 through 6)

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Document Type: Study Protocol: Protocol V6.0 (Incorporating Amendments 1-5)

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Document Type: Statistical Analysis Plan

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Other Identifiers

C-144-01

Identifier Type: -

Identifier Source: org_study_id