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

NCT03108495 | Terminated Phase 2 DMC FDA Drug

• 2 other identifiers: C-145-042024-510634-41-00
• Study Type: interventional
• Target: 210
• Locations: 8 countries
• Sites: 43

Brief Summary

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

Conditions

Cervical Carcinoma

Keywords

LN-145; Cell Therapy; Autologous Adoptive Cell Transfer; Autologous Adoptive Cell Therapy; Cellular Immuno-therapy; Tumor Infiltrating Lymphocytes; TIL; IL-2; Pembrolizumab

Outcome Measures

Primary Outcomes (4)

• Cohort 1 and 2: Objective Response Rate

  To evaluate the efficacy of LN-145 in patients with recurrent, metastatic, or persistent cervical carcinoma based on the objective response rate (ORR) as assessed by the Investigator per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1

  Up to 60 months

• Cohort 3: Adverse Events

  To characterize the safety profile of LN-145 in combination with pembrolizumab in patients with recurrent, metastatic, or persistent cervical carcinoma as assessed by incidence of adverse events.

  Up to 60 months

• Cohort 4: Efficacy and Adverse Events

  To explore the efficacy and safety profile of LN-145 in previously enrolled patients with recurrent, metastatic, or persistent cervical carcinoma

  Up to 60 months

• Cohort 5: Efficacy and Adverse Events

  To explore the efficacy and safety profile of LN-145 in re-treated patients with recurrent, metastatic, or persistent cervical carcinoma

  Up to 60 months

Secondary Outcomes (10)

• Cohort 1 and 2: Duration of Response

  Up to 60 months

• Cohort 1 and 2: Disease Control Rate

  Up to 60 months

• Cohort 1 and 2: Progression-Free Survival

  Up to 60 months

• Cohort 1 and 2: Overall Survival

  Up to 60 months

• Cohort 1 and 2: Adverse Events

  Up to 60 months

Study Arms (5)

Cohort 1 LN-145 monotherapy

EXPERIMENTAL

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

Biological: LN-145

Cohort 2 LN-145 monotherapy

EXPERIMENTAL

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.

Biological: LN-145

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

EXPERIMENTAL

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.

Biological: LN-145 + pembrolizumab

Cohort 4 - Non-enrolling Cohort

EXPERIMENTAL

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.

Biological: LN-145

Cohort 5 Retreatment Cohort

EXPERIMENTAL

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

Biological: LN-145

Interventions

LN-145 BIOLOGICAL

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

Also known as: TIL, autologous tumor infiltrating lymphocytes

Cohort 1 LN-145 monotherapy; Cohort 2 LN-145 monotherapy; Cohort 4 - Non-enrolling Cohort; Cohort 5 Retreatment Cohort

LN-145 + pembrolizumab 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.

Also known as: TIL, autologous tumor infiltrating lymphocytes; pembrolizumab (anti-PD-1 immunotherapy)

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

Eligibility Criteria

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

You may qualify if:

• To be eligible for the study, patients must meet ALL of the following criteria prior to participation:
• 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.
• 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.
• 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)
• At least one measurable target lesion, as defined by RECIST v1.1.
• 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
• 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.
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Must have adequate organ function.
• 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

You may not qualify if:

• Patients who meet any of the following criteria are not eligible for participation in this study:
• 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.
• Patients who require ongoing systemic steroid therapy (\> 10 mg/day of prednisone or other steroid equivalent dose).
• 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).
• 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)
• 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.
• 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
• Patients who have any form of primary immunodeficiency (such as severe combined immunodeficiency \[SCID\] or acquired immunodeficiency syndrome \[AIDS\])
• Patients who have a diagnosis of end-stage renal disorder requiring hemodialysis
• Patients who have a left ventricular ejection fraction (LVEF) \< 45% or who are New York Heart Association (NYHA) Class 2 or higher.
• 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 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)
• Patients who are of the following protected classes will be excluded, including:

Sponsors & Collaborators

• Iovance Biotherapeutics, Inc.: lead

Study Sites (43)

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

Phoenix, Arizona, 85013, United States

Location

University of Southern California

Los Angeles, California, 90033, United States

Location

University of California San Diego

San Diego, California, 92093, United States

Location

Sylvester Comprehensive Cancer Center

Miami, Florida, 33136, United States

Location

University of Florida Health Cancer Center

Orlando, Florida, 32806, United States

Location

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

Tampa, Florida, 33612, United States

Location

Augusta University

Augusta, Georgia, 30912-0003, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

James Graham Brown Cancer Center

Louisville, Kentucky, 40202, United States

Location

LSU Health Sciences Center

New Orleans, Louisiana, 70112, United States

Location

The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, 21287-0013, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Rutgers University

Newark, New Jersey, 07103, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

The Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, 73104, United States

Location

Allegheny Health

Pittsburgh, Pennsylvania, 15224, United States

Location

UPMC Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

Location

Avera Medical Group Oncology

Sioux Falls, South Dakota, 57105, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

University of Virginia

Charlottesville, Virginia, 22908, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53225, United States

Location

Centre Hospitalier Lyon Sud

Pierre-Bénite, Auvergne-Rhône-Alpes, 69495, France

Location

Centre Léon Bérard

Lyon, 69008, France

Location

Gustave Roussy Cancer Campus

Villejuif, 94805, France

Location

Universitätsklinikum Erlangen

Erlangen, Bavaria, 91054, Germany

Location

Universitätsklinikum Carl Gustav Carus

Dresden, Saxony, 01307, Germany

Location

Istituto Europeo di Oncologia

Miano, Milano, 20141, Italy

Location

Academisch Medisch Centrum

Amsterdam, AZ, 1105, Netherlands

Location

Clínica Universidad de Navarra

Pamplona, Navarre, 31008, Spain

Location

Hospital Universitari Vall d'Hebrón

Barcelona, 08035, Spain

Location

Institut Català d'Oncologia

Barcelona, 08908, Spain

Location

Hospital General Universitario Gregorio Marañon

Madrid, 28007, Spain

Location

Hospital Universitario Madrid Sanchinarro

Madrid, 28050, Spain

Location

Inselspital

Bern, CH-3010, Switzerland

Location

Centre Hospitalier Universitaire Vaudois Lausanne - Centre Pluridisciplinaire d'Oncologie

Lausanne, Switzerland

Location

Bristol Haematology and Oncology Centre

Bristol, England, BS2 8ED, United Kingdom

Location

Sarah Cannon Research Institute London

London, England, W1G 6AD, United Kingdom

Location

University College London Hospitals NHS Foundation Trust

London, England, W1G 6BW, United Kingdom

Location

NHS Greater Glasgow and Clyde

Glasgow, Scotland, G12 0YN, United Kingdom

Location

Guy's & St.Thomas NHS Foundation Trust

London, SE1 9RT, United Kingdom

Location

MeSH Terms

Conditions

Uterine Cervical Neoplasms

Interventions

Toll-Like Receptor 1; pembrolizumab

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Intervention Hierarchy (Ancestors)

Toll-Like Receptors; Receptors, Pattern Recognition; Receptors, Immunologic; Receptors, Cell Surface; Membrane Proteins; Proteins; Amino Acids, Peptides, and Proteins

Study Officials

• Iovance Medical Monitor

  Iovance Biotherapeutics, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 27, 2017
• First Posted: April 11, 2017
• Study Start: June 22, 2017
• Primary Completion: August 22, 2025
• Study Completion: August 22, 2025
• Last Updated: September 17, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

FR (3); DE (2); NL (1); CH (2); IT (1); ES (5); US (24); GB (5)