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

Metastatic Melanoma Clinical Trial

— LN-144  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02360579
• Other study ID #: C-144-01
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: September 2015
• Est. completion date: January 15, 2025

Study information

• Verified date: July 2023
• Source: Iovance Biotherapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 178
• Est. completion date: January 15, 2025
• Est. primary completion date: January 15, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Melanoma
• Metastatic Melanoma

Intervention

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.

Locations

Country	Name	City	State
France	Hôpital Dupuytren	Limoges cedex	Limousin
France	Centre Léon Bérard	Lyon	Rhone-alpes
France	Centre Hospitalier Lyon Sud	Pierre-Bénite	Rhone-alpes
France	Gustave Roussy Cancer Campus	Villejuif Cedex	Ile-de-france
Germany	Universitätsklinikum Carl Gustav Carus	Dresden	Sachsen
Germany	Universitätsklinikum Erlangen	Erlangen	Bayern
Germany	Universitätsklinikum Halle	Halle/Saale	Sachsen-anhalt
Germany	Universitaetsklinikum Heidelberg	Heidelberg	Baden-wuerttemberg
Germany	Universitätsklinikum Leipzig	Leipzig	Sachsen
Germany	Universitätsklinikum Schleswig-Holstein - Campus Lübeck	Lübeck	Schleswig-holstein
Germany	Klinikum Rechts der Isar der Technischen Universität München	München	Bayern
Germany	Universitaetsklinikum Tuebingen (UKT) - Suedwestdeutschen Tumorzentrum - Zentrum für Neuroonkologie	Tübingen	Baden-wuerttemberg
Germany	Universitätsklinikum Würzburg	Würzburg
Hungary	Szegedi Tudomanyegyetem Szent-Györgyi Albert Klinikai Központ	Szeged	Csongrad
Italy	Centro di Riferimento Oncologico di Aviano	Aviano	Pordenone
Italy	Istituto di Candiolo - Fondazione del Piemonte per l'Oncologia	Candiolo	Torino
Italy	Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori	Meldola	Forli-cesena
Italy	Istituto Europeo di Oncologia	Milano
Italy	Istituto Nazionale Tumori IRCCS Fondazione Pascale	Napoli
Spain	Hospital Clinic de Barcelona	Barcelona
Spain	Hospital Universitari Vall d'Hebrón	Barcelona
Spain	Institut Català d'Oncologia	Barcelona
Spain	HM Centro Integral Oncológico Clara Campal	Madrid
Spain	Hospital 12 de Octubre	Madrid
Spain	Hospital General Universitario Gregorio Marañon	Madrid
Spain	Hospital Universitario Quirónsalud Madrid	Madrid
Spain	Clínica Universidad de Navarra	Pamplona	Navarra
Spain	Consorci Hospital General Universitari de València	Valencia
Switzerland	Inselspital	Bern
Switzerland	Centre Hospitalier Universitaire Vaudois Lausanne - Centre Pluridisciplinaire d'Oncologie	Lausanne
United Kingdom	Addenbrooke's Hospital	Cambridge
United Kingdom	Beatson West of Scotland Cancer Centre	Glasgow	Scotland
United Kingdom	Royal Marsden NHS Trust	London	England
United Kingdom	Sarah Cannon Research Institute London	London
United States	University of Colorado Cancer Center	Aurora	Colorado
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Indiana University	Indianapolis	Indiana
United States	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	James Graham Brown Cancer Center	Louisville	Kentucky
United States	University of Miami	Miami	Florida
United States	Mount Sinai Comprehensive Cancer Center	Miami Beach	Florida
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
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	Yale Cancer Center	New Haven	Connecticut
United States	New York University Langone Medical Center	New York	New York
United States	University of Florida Health Cancer Center	Orlando	Florida
United States	Thomas Jefferson University	Philadelphia	Pennsylvania
United States	University of Pittsburgh Medical Center - Hillman Cancer Center	Pittsburgh	Pennsylvania
United States	Providence Cancer Center Oncology and Hematology Care Clinic	Portland	Oregon
United States	Virginia Commonwealth University	Richmond	Virginia
United States	California Pacific Medical Center	San Francisco	California
United States	Seattle Cancer Care Alliance	Seattle	Washington
United States	University of South Florida H. Lee Moffitt Cancer Center and Research Institute	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Iovance Biotherapeutics, Inc.

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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 Blinded Independent Review Committee (BIRC) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1	Every 6 weeks for 6 months, then every 3 months for a maximum of 60 months
Secondary	Disease Assessment for Duration of Response	Evaluate the efficacy endpoints of duration of response (DOR) by the BIRC and by the investigator per RECIST v1.1	Every 6 weeks for 6 months, then every 3 months for a maximum of 60 months
Secondary	Disease Assessment for Disease Control Rate	Evaluate the efficacy endpoints of disease control rate (DCR) as assessed by the BIRC and by the investigator per RECIST v1.1	Every 6 weeks for 6 months, then every 3 months for a maximum of 60 months
Secondary	Disease Assessment for Progression-Free Survival	Evaluate the efficacy endpoints of progression-free survival (PFS) as assessed by the BIRC and by the investigator per RECIST v1.1	Every 6 weeks for 6 months, then every 3 months for a maximum of 60 months
Secondary	Overall Survival	Evaluate overall survival (OS) and objective response rate (ORR) by the investigator	Until death or up to 60 months
Secondary	Adverse Events	Incidence rate of treatment-emergent adverse events (AEs) and serious AEs by severity and relationship to Lifileucel (LN-144).	Maximum 60 months