Lifileucel With Reduced Dose Fludarabine/Cyclophosphamide Lymphodepletion and Interleukin-2 for the Treatment of Patients With Unresectable or Metastatic Melanoma

NCT06151847 | Completed Phase 2 DMC FDA Drug

• 4 other identifiers: STUDY00150697NCI-2023-09309IIT-2022-LDTILP30CA168524
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial tests how well lifileucel, with reduce dose fludarabine and cyclophosphamide for lymphodepletion and interleukin-2, work for treating patients with melanoma that cannot be removed by surgery (unresectable) or that has spread from where it first started (primary site) to other places in the body (metastatic).Lifileucel is made up of specialized immune cells called lymphocytes or T cells that are taken from a patient's tumor, grown in a manufacturing facility and infused back into the preconditioned patient to attack the tumor. Giving Lifileucel with a reduced dose of fludarabine and cyclophosphamide for lymphodepletion and interleukin -2 is being studied in patients with unresectable or metastatic melanoma.

Conditions

Clinical Stage IV Cutaneous Melanoma AJCC v8; Metastatic Melanoma; Pathologic Stage IIIC Cutaneous Melanoma AJCC v8; Unresectable Melanoma

Outcome Measures

Primary Outcomes (1)

• Percentage of total T-cell receptor (TCR) populations shared between the TIL product and peripheral blood mononuclear cells (PBMCs)

  The TCR population is calculated as the frequencies of unique CDR3 sequences as measured by HTBIvc assay. Will be summarized with respect to mean and standard deviation. The percentage changes will also be presented with respect to visual diagrams for each person, e.g., waterfall plot

  At day + 42

Secondary Outcomes (7)

• Safety: Incidence of treatment emergent adverse events

  From start of treatment to 6 months after TIL

• Safety: Incidence of serious adverse events

  From start of treatment to 6 months after TIL

• Transfusion requirements

  From start of treatment to 6 months after TIL

• Length of hospital stay

  From start of treatment to 6 months after TIL

• Overall response rate

  From start of treatment until the end of treatment, up to 2 years

Study Arms (1)

Treatment (Lifileucel)

EXPERIMENTAL

Lifileucel (LN-144) is an autologous Tumor Infiltrating Lymphocytes (TIL) cell therapy. A tumor sample is resected from each patient for lifileucel manufacturing. Patients then receive the lifileucel regimen which consists of a reduced dose non-myeloablative lymphodepletion, lifileucel infusion followed by interleukin-2.

Procedure: Biospecimen Collection; Drug: Cyclophosphamide; Procedure: Echocardiography; Drug: Fludarabine; Biological: Interleukin-2; Biological: Lifileucel; Procedure: Magnetic Resonance Imaging; Procedure: Multigated Acquisition Scan; Procedure: Tumor Resection

Interventions

Biospecimen Collection PROCEDURE

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: Biological Sample Collection, Biospecimen Collected, Specimen Collection, Undergo blood sample collection

Treatment (Lifileucel)

Cyclophosphamide DRUG

Given IV

Also known as: (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Asta B 518, B-518, Carloxan, Ciclofosfamida, Ciclofosfamide, Cicloxal, Clafen, Claphene, CP monohydrate, CTX, CYCLO-cell, Cycloblastin, Cycloblastine, Cyclophospham, Cyclophosphamid monohydrate, Cyclophosphamide Monohydrate, Cyclophosphamidum, Cyclophosphan, Cyclophosphane, Cyclophosphanum, Cyclostin, Cyclostine, Cytophosphan, Cytophosphane, Cytoxan, Fosfaseron, Genoxal, Genuxal, Ledoxina, Mitoxan, Neosar, Revimmune, Syklofosfamid, WR- 138719, WR-138719

Treatment (Lifileucel)

Echocardiography PROCEDURE

Undergo echocardiography

Also known as: EC

Treatment (Lifileucel)

Fludarabine DRUG

Given IV

Also known as: Fluradosa

Treatment (Lifileucel)

Interleukin-2 BIOLOGICAL

Given IV

Also known as: Epidermal Thymocyte Activating Factor, ETAF, hIL-2, IL-2, IL2, IL2 Protein, Interleukin 2, Interleukin 2 Precursor, Interleukin II, Lymphocyte Mitogenic Factor, Mitogenic Factor, Ro-236019, T Cell Growth Factor, T-Cell Growth Factor, TCGF, Thymocyte Stimulating Factor, TSF

Treatment (Lifileucel)

Lifileucel BIOLOGICAL

Given IV

Also known as: Autologous TIL LN-144, Autologous Tumor Infiltrating Lymphocytes LN-144, Contego, Lifileuecel, LN-144

Treatment (Lifileucel)

Magnetic Resonance Imaging PROCEDURE

Undergo MRI

Also known as: Magnetic Resonance, Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging

Treatment (Lifileucel)

Multigated Acquisition Scan PROCEDURE

Undergo MUGA scan

Also known as: Blood Pool Scan, Equilibrium Radionuclide Angiography, Gated Blood Pool Imaging, Gated Heart Pool Scan, MUGA, MUGA Scan, Multi-Gated Acquisition Scan, Radionuclide Ventriculogram Scan, Radionuclide Ventriculography, RNVG, SYMA Scanning, Synchronized Multigated Acquisition Scanning

Treatment (Lifileucel)

Tumor Resection PROCEDURE

Undergo tumor resection

Treatment (Lifileucel)

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males and females age ≥ 18 years Enrollment of patients ≥ 70 years of age may be allowed at principal investigator discretion.
• Eastern Cooperative Oncology Group (ECOG) performance status 0 - 1
• At least one measurable target lesion, as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1
• 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 lesion
• Women of childbearing potential must have a negative serum pregnancy test 48 hours prior to initiating treatment
• Patients with unresectable or metastatic melanoma (stage IIIc or stage IV)
• Patients must have progressed following 1-3 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 mitogen-activated extracellular signal-regulated kinase (MEK) inhibitor
• 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)
• Adequate hematologic and organ function
• Patients must have recovered from all prior therapy-related adverse events (AEs) to ≤ grade 1 (per Common Terminology Criteria for Adverse Events \[CTCAE\] version \[v\] 5.0), except for alopecia or vitiligo, prior to enrollment (tumor resection)
• Patients with documented ≥ grade 2 diarrhea or colitis because 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
• Patients with immunotherapy-related endocrinopathies stable for at least 6 weeks (eg, hypothyroidism), and controlled with hormonal replacement (non-corticosteroids), are allowed
• Patients must have a washout period of ≥ 28 days from prior anticancer therapy(ies) to the start of the planned reduced dose lymphodepletion (RDL) preconditioning regimen:
• Targeted therapy: MEK/BRAF or other targeted agents
• Chemotherapy

You may not qualify if:

• Current or anticipating use of other anti-neoplastic or investigational agents while participating in this study
• Is pregnant or breastfeeding
• Patients who have active medical illness(es) that would pose increased risk for study participation, including active systemic infections requiring systemic antibiotics, coagulation disorders, or other active major medical illnesses of the cardiovascular, respiratory, or immune system
• 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 Lifileucel or other study drugs
• 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 who have a documented forced expiratory volume in 1 second (FEV1) of ≤ 60%
• Patients who have had another primary malignancy within the previous 3 years (except for carcinoma in situ of the breast, cervix, or bladder; localized prostate cancer; and non-melanoma skin cancer that has been adequately treated)
• Patients with symptomatic and/or untreated brain metastases (of any size and any number)

Sponsors & Collaborators

• University of Kansas Medical Center: lead
• National Cancer Institute (NCI): collaborator
• Iovance Biotherapeutics, Inc.: collaborator

Study Sites (1)

University of Kansas Cancer Center

Kansas City, Kansas, 66160, United States

Location

Related Publications (1)

• Mushtaq MU, Abdelhakim H, Selby L, Shahzad M, Abhyankar SH, McGuirk JP, Doolittle GC. Reduced dose fludarabine and cyclophosphamide lymphodepletion before tumor-infiltrating lymphocyte therapy in melanoma. Future Oncol. 2025 Jun;21(13):1631-1637. doi: 10.1080/14796694.2025.2498842. Epub 2025 May 9.

  PMID: 40343719 DERIVED

MeSH Terms

Conditions

Melanoma

Interventions

Specimen Handling; Cyclophosphamide; fludarabine; Interleukin-2; 4-toluenesulfonyl fluoride; lifileucel; Magnetic Resonance Spectroscopy; Transurethral Resection of Bladder

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

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Interleukins; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Lymphokines; Proteins; Biological Factors; Spectrum Analysis; Chemistry Techniques, Analytical; Urologic Surgical Procedures; Urogenital Surgical Procedures; Surgical Procedures, Operative

Study Officials

• Muhammad Umair Mushtaq

  University of Kansas

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: November 17, 2023
• First Posted: November 30, 2023
• Study Start: December 21, 2023
• Primary Completion: July 10, 2025
• Study Completion: July 10, 2025
• Last Updated: April 30, 2026

Record last verified: 2026-04

Locations

US (1)