Study of LN-145, Autologous Tumor Infiltrating Lymphocytes in the Treatment of Patients With Cervical Carcinoma

NCT ID: NCT03108495

Last Updated: 2025-09-17

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE2

Total Enrollment

210 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-06-22

Study Completion Date

2025-08-22

Brief Summary

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Prospective, multicenter, single-arm, open label, interventional study evaluating adoptive cell therapy (ACT) with autologous tumor infiltrating lymphocytes (TIL) infusion (LN-145) followed by IL-2 after a non-myeloablative (NMA) lymphodepletion preparative regimen for the treatment of patients with recurrent, metastatic, or persistent cervical carcinoma

Detailed Description

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LN-145 is an adoptive cell transfer therapy that utilizes an autologous TIL manufacturing process, as originally developed by the NCI, for the treatment of patients with recurrent, metastatic, or persistent cervical carcinoma. The cell transfer therapy used in this study involves patients receiving a NMA lymphocyte depleting preparative regimen, followed by infusion of autologous TIL followed by the administration of a regimen of IL-2.

Conditions

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Cervical Carcinoma

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Cohort 1 LN-145 monotherapy

Post-NMA lymphodepletion, patients are infused with their autologous TIL (LN-145) followed by IL-2 administration.

Group Type EXPERIMENTAL

LN-145

Intervention Type BIOLOGICAL

A tumor sample is resected from each patient and cultured ex vivo to expand the population of tumor infiltrating lymphocytes.

Cohort 2 LN-145 monotherapy

Patients previously treated with an antiprogrammed cell death protein-1 (PD-1) or anti-programmed death-ligand 1 (PD-L1) checkpoint inhibitor: Post-NMA lymphodepletion, patients are infused with their autologous TIL (LN-145) followed by IL-2 administration.

Group Type EXPERIMENTAL

LN-145

Intervention Type BIOLOGICAL

A tumor sample is resected from each patient and cultured ex vivo to expand the population of tumor infiltrating lymphocytes.

Cohort 3 - Combination Arm (TIL + Pembrolizumab) - US Only

Patients will be administered with pembrolizumab, followed by NMA lymphodepletion, then infused with their autologous TIL (LN-145) followed by pembrolizumab every 3 or 6 weeks post IL-2 administration up to 24 months.

Group Type EXPERIMENTAL

LN-145 + pembrolizumab

Intervention Type BIOLOGICAL

A tumor sample is resected from each patient and cultured ex vivo to expand the population of tumor infiltrating lymphocytes. The first dose of anti-PD-1 immunotherapy will be administered following tumor resection.

Cohort 4 - Non-enrolling Cohort

Cohort includes patient population not meeting inclusion criteria in cohort 1 and 2. Post-NMA lymphodepletion, patients are infused with their autologous TIL (LN-145) followed by IL-2 administration.

Group Type EXPERIMENTAL

LN-145

Intervention Type BIOLOGICAL

A tumor sample is resected from each patient and cultured ex vivo to expand the population of tumor infiltrating lymphocytes.

Cohort 5 Retreatment Cohort

Patients who have been previously treated with LN-145 may be given a second treatment with TIL.

Group Type EXPERIMENTAL

LN-145

Intervention Type BIOLOGICAL

A tumor sample is resected from each patient and cultured ex vivo to expand the population of tumor infiltrating lymphocytes.

Interventions

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LN-145

A tumor sample is resected from each patient and cultured ex vivo to expand the population of tumor infiltrating lymphocytes.

Intervention Type BIOLOGICAL

LN-145 + pembrolizumab

A tumor sample is resected from each patient and cultured ex vivo to expand the population of tumor infiltrating lymphocytes. The first dose of anti-PD-1 immunotherapy will be administered following tumor resection.

Intervention Type BIOLOGICAL

Other Intervention Names

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TIL, autologous tumor infiltrating lymphocytes TIL, autologous tumor infiltrating lymphocytes; pembrolizumab (anti-PD-1 immunotherapy)

Eligibility Criteria

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Inclusion Criteria

To be eligible for the study, patients must meet ALL of the following criteria prior to participation:

1. 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.
2. Must have recurrent, metastatic, or persistent squamous cell carcinoma (SCC), adenosquamous carcinoma (ASC), or adenocarcinoma (AC) of the cervix that is not amenable to curative treatment with surgery and/or radiation therapy.
3. 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)
4. At least one measurable target lesion, as defined by RECIST v1.1.
5. Cohort 1 and Cohort 2: Progression during or following at least one, but no more than three, prior systemic chemotherapeutic treatments for recurrent, metastatic, or persistent cervical carcinoma

* A line of systemic therapy is defined as any chemotherapy or multiple-agent chemotherapy regimen that was administered for recurrent, metastatic, or persistent SCC, ASC, or AC of the cervix.
* A bevacizumab and chemotherapy combination is encouraged as a prior line of treatment.
* Neither chemoradiation, nor chemotherapy in the neoadjuvant or adjuvant settings are considered as a prior line of systemic therapy.

Cohort 2: Must also have previously received treatment with a checkpoint inhibitor (ie, PD-1, PD-L1\]) in the setting of recurrent, metastatic, or persistent disease either as monotherapy or in combination (eg, in combination with chemotherapy or another immune agent)

Cohort 3 (United States only): Must have not received any therapies other than prior chemoradiation or surgery for loco-regional disease
6. Any prior therapy directed at the malignant tumor, including chemotherapy, biologic/targeted agents, and immunologic agents must be discontinued at least 28 days prior to tumor resection.
7. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
8. Must have adequate organ function.
9. Patient has no evidence of any active viral, bacterial, or fungal infection requiring ongoing systemic treatment. Patients must be seronegative for the human immunodeficiency virus (HIV). Patients with acute or chronic hepatitis infections may be enrolled if the viral load by nucleic acid amplification test (NAAT) is undetectable with/without active treatment
10. Patients of childbearing potential must be willing to take the appropriate precaution to avoid pregnancy 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.
11. Prior to study Enrollment (tumor resection), patient must have documentation of radiological disease progression after the most recent therapy

Exclusion Criteria

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

1. Patients who have received an organ allograft or prior cell transfer therapy except for prior LN-145 therapy in the setting of re-treatment only.
2. Patients who require ongoing systemic steroid therapy (\> 10 mg/day of prednisone or other steroid equivalent dose).
3. Patients who currently have prior therapy-related toxicities Grade \> 1 according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0; except for peripheral neuropathy, alopecia, or vitiligo prior to Enrollment (tumor resection).
4. . Patients who have a history of hypersensitivity to any component or excipient of LN-145 or other study drugs:

• NMA-LD preparative regimen (cyclophosphamide, mesna, and fludarabine)
5. Patients who have active systemic infections, coagulation disorders, or other active major medical illness(es) of the cardiovascular, respiratory, or immune system, including evidence in the medical history of urinary tract obstruction, a positive cardiac stress test, myocardial infarction, cardiac arrhythmia, obstructive or restrictive pulmonary disease, or other conditions that in the opinion of the Investigator would increase the risk of participation.
6. 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 preparative regimen
7. Patients who have any form of primary immunodeficiency (such as severe combined immunodeficiency \[SCID\] or acquired immunodeficiency syndrome \[AIDS\])
8. Patients who have a diagnosis of end-stage renal disorder requiring hemodialysis
9. Patients who have a left ventricular ejection fraction (LVEF) \< 45% or who are New York Heart Association (NYHA) Class 2 or higher.
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 (except for curatively treated localized malignancy that has not required treatment for \> 1 year, and in the judgement of the Investigator, does not pose a significant risk of recurrence including, but not limited to, non-melanoma skin cancer or bladder cancer)
12. Patients who are of the following protected classes will be excluded, including:

* Pregnant, parturient, or breastfeeding women
* Persons who are hospitalized without consent or those deprived of liberty because of a judiciary or administrative decision
* Patients with a legal protection measure or a person who cannot express his/her consent
* Patients in emergency situations who cannot consent to the study
13. Patients who have received a live or attenuated vaccine within 28 days prior to beginning the NMA-LD preparative regimen
14. Patients whose cancer requires immediate attention or who would otherwise suffer a disadvantage by participating in this study
15. Cohort 1 and Cohort 3: Patients who have received prior treatment with immunotherapy (eg, PD-1, PD-L1, or anti-cytotoxic T lymphocyte-associated antigen-4 \[CTLA-4\] antibodies)
16. Patients who have Grade ≥ 2 hemorrhage within 14 days prior to Enrollment (tumor resection)
17. Cohort 3: Patients may not have active or prior documented autoimmune or inflammatory disorders (including pneumonitis, inflammatory bowel disease \[eg, colitis or Crohn's disease\], diverticulitis \[with the exception of diverticulosis\], systemic lupus erythematosus, sarcoidosis syndrome, or Wegener syndrome \[granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc.\]).
Minimum Eligible Age

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Iovance Biotherapeutics, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Iovance Medical Monitor

Role: STUDY_DIRECTOR

Iovance Biotherapeutics, Inc.

Locations

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St. Joseph's Hospital and Medical Center Center For Women's Health

Phoenix, Arizona, United States

Site Status

University of Southern California

Los Angeles, California, United States

Site Status

University of California San Diego

San Diego, California, United States

Site Status

Sylvester Comprehensive Cancer Center

Miami, Florida, United States

Site Status

University of Florida Health Cancer Center

Orlando, Florida, United States

Site Status

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

Tampa, Florida, United States

Site Status

Augusta University

Augusta, Georgia, United States

Site Status

University of Chicago

Chicago, Illinois, United States

Site Status

James Graham Brown Cancer Center

Louisville, Kentucky, United States

Site Status

LSU Health Sciences Center

New Orleans, Louisiana, United States

Site Status

The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, United States

Site Status

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

Karmanos Cancer Institute

Detroit, Michigan, United States

Site Status

Rutgers University

Newark, New Jersey, United States

Site Status

Roswell Park Cancer Institute

Buffalo, New York, United States

Site Status

Cleveland Clinic

Cleveland, Ohio, United States

Site Status

The Ohio State University Comprehensive Cancer Center

Columbus, Ohio, United States

Site Status

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, United States

Site Status

Allegheny Health

Pittsburgh, Pennsylvania, United States

Site Status

UPMC Cancer Center

Pittsburgh, Pennsylvania, United States

Site Status

Avera Medical Group Oncology

Sioux Falls, South Dakota, United States

Site Status

MD Anderson Cancer Center

Houston, Texas, United States

Site Status

University of Virginia

Charlottesville, Virginia, United States

Site Status

Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Site Status

Centre Hospitalier Lyon Sud

Pierre-Bénite, Auvergne-Rhône-Alpes, France

Site Status

Centre Léon Bérard

Lyon, , France

Site Status

Gustave Roussy Cancer Campus

Villejuif, , France

Site Status

Universitätsklinikum Erlangen

Erlangen, Bavaria, Germany

Site Status

Universitätsklinikum Carl Gustav Carus

Dresden, Saxony, Germany

Site Status

Istituto Europeo di Oncologia

Miano, Milano, Italy

Site Status

Academisch Medisch Centrum

Amsterdam, AZ, Netherlands

Site Status

Clínica Universidad de Navarra

Pamplona, Navarre, Spain

Site Status

Hospital Universitari Vall d'Hebrón

Barcelona, , Spain

Site Status

Institut Català d'Oncologia

Barcelona, , Spain

Site Status

Hospital General Universitario Gregorio Marañon

Madrid, , Spain

Site Status

Hospital Universitario Madrid Sanchinarro

Madrid, , Spain

Site Status

Inselspital

Bern, , Switzerland

Site Status

Centre Hospitalier Universitaire Vaudois Lausanne - Centre Pluridisciplinaire d'Oncologie

Lausanne, , Switzerland

Site Status

Bristol Haematology and Oncology Centre

Bristol, England, United Kingdom

Site Status

Sarah Cannon Research Institute London

London, England, United Kingdom

Site Status

University College London Hospitals NHS Foundation Trust

London, England, United Kingdom

Site Status

NHS Greater Glasgow and Clyde

Glasgow, Scotland, United Kingdom

Site Status

Guy's & St.Thomas NHS Foundation Trust

London, , United Kingdom

Site Status

Countries

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United States France Germany Italy Netherlands Spain Switzerland United Kingdom

Other Identifiers

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2024-510634-41-00

Identifier Type: CTIS

Identifier Source: secondary_id

C-145-04

Identifier Type: -

Identifier Source: org_study_id

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