Study of LN-145/LN-145-S1 Autologous Tumor Infiltrating Lymphocytes in the Treatment of Squamous Cell Carcinoma of the Head & Neck

NCT ID: NCT03083873

Last Updated: 2023-10-12

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

64 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-01-09

Study Completion Date

2022-08-08

Brief Summary

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Multicenter, multicohort, non-randomized, prospective, open label, interventional study evaluating adoptive cell therapy (ACT) with autologous tumor infiltrating lymphocytes (TIL) infusion (LN-145/LN-145-S1) followed by IL-2 after a non-myeloablative (NMA) lymphodepletion preparative regimen for the treatment of patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck

Detailed Description

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LN-145/LN-145-S1 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 and/or metastatic squamous cell carcinoma of the head and neck. The cell transfer therapy used in this study involves patients receiving a NMA lymphodepletion preparative regimen, followed by infusion of autologous TIL followed by the administration of a regimen of IL-2.

Conditions

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Squamous Cell Carcinoma of the Head and Neck

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

Treatment with LN-145, Generation 1 (Gen 1), non-cryopreserved 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. After NMA lymphodepletion, patients are infused with their autologous TIL (LN-145) followed by IL-2 administration.

Cohort 2

Treatment with LN-145 Generation 2 (Gen 2), cryopreserved 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. After NMA lymphodepletion, patients are infused with their autologous TIL (LN-145) followed by IL-2 administration.

Cohort 3

Treatment with LN-145 Generation 3 (Gen 3), cryopreserved 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. After NMA lymphodepletion, patients are infused with their autologous TIL (LN-145) followed by IL-2 administration.

Cohort 4

Treatment with LN-145-S1 cryopreserved TIL

Group Type EXPERIMENTAL

LN-145-S1

Intervention Type BIOLOGICAL

A tumor sample is resected from each patient and cultured ex vivo to expand the population of tumor infiltrating lymphocytes. After NMA lymphodepletion, patients are infused with autologous TIL (LN-145-S1) followed by IL-2 administration.

Cohort 5

LN-145 cryopreserved/LN-145-S1 cryopreserved TIL re-treatment

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

LN-145-S1

Intervention Type BIOLOGICAL

A tumor sample is resected from each patient and cultured ex vivo to expand the population of tumor infiltrating lymphocytes. After NMA lymphodepletion, patients are infused with autologous TIL (LN-145-S1) followed by IL-2 administration.

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

Intervention Type BIOLOGICAL

LN-145-S1

A tumor sample is resected from each patient and cultured ex vivo to expand the population of tumor infiltrating lymphocytes. After NMA lymphodepletion, patients are infused with autologous TIL (LN-145-S1) followed by IL-2 administration.

Intervention Type BIOLOGICAL

Other Intervention Names

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TIL, autologous tumor infiltrating lymphocytes TIL, autologous tumor infiltrating lymphocytes

Eligibility Criteria

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Inclusion Criteria

* Must be greater than 18 years of age at the time of consent.
* Must have recurrent and/or metastatic, squamous cell carcinoma of the head and neck (both HPV-positive and -negative)
* Must have at least 1 lesion that is resectable for TIL generation.
* Must have measurable disease as defined by RECIST v1.1 following the surgical resection.
* Must have received at least 1 and no more than 3 lines of prior systemic immunotherapy and/or chemotherapeutic treatments for HNSCC.
* Any prior therapy directed at the malignant tumor must be discontinued at least 28 days prior to lymphodepletion.
* Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
* Patients must be seronegative for the human immunodeficiency virus.
* Patients seropositive for hepatitis B virus surface antigen (HBsAg), hepatitis B core antibody (anti-HBc), or hepatitis C virus (anti-HCV) indicating acute or chronic infection may be enrolled if the viral load by polymerase chain reaction (PCR) is undetectable with/without active treatment
* Patients of childbearing potential and patients whose sexual partners are of childbearing potential must be willing to practice an approved method of highly effective birth control starting at the time of informed consent and for 1 year after the completion of the study treatment regimen.

Exclusion Criteria

* Patients who have received an organ allograft or prior cell transfer therapy within the past 20 years.
* Patients who are on a systemic steroid therapy (greater than 10 mg of prednisone or equivalent). Patients receiving steroids as replacement therapy for adrenocortical insufficiency at \< 10 mg of prednisone or other steroid equivalent daily may be eligible.
* Prior therapy-related toxicities Grade ≥ 1 according to Common Toxicity Criteria for Adverse Events (CTCAE) v4.03
* Patients with documented Grade ≥ 2 diarrhea or colitis as a result of previous immunotherapy within six months from screening.
* Patients who have a contraindication to or history of hypersensitivity reaction to cyclophosphamide, mesna, fludarabine, IL-2, antibiotics of the aminoglycoside group (ie, gentamicin or streptomycin; excluding those who are skin-test negative for gentamicin hypersensitivity), any component of the TIL infusion product formulation including dimethylsulfoxide (DMSO), human serum albumin (HSA), IL-2, and dextran-40.
* Patients with active systemic infections, coagulation disorders or other active major medical illnesses of the cardiovascular, respiratory or immune system.
* Patients with symptomatic and/or untreated brain metastases.
* Have any form of primary or acquired immunodeficiency syndrome, such as severe combined immunodeficiency disease or acquired immune deficiency syndrome (AIDS).
* 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 had another primary malignancy within the previous 3 years.
* Patients who are pregnant, parturient, or breastfeeding women.
* Patients who have received a live or attenuated vaccine within 28 days of the NMA-LD regimen.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

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 Biotherapeutics Medical Monitor

Role: STUDY_DIRECTOR

Iovance Biotherapeutics

Locations

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University of Alabama

Birmingham, Alabama, United States

Site Status

University of California San Diego

La Jolla, California, United States

Site Status

University of California, Los Angeles

Los Angeles, California, United States

Site Status

University of Southern California

Los Angeles, California, United States

Site Status

University of Colorado

Aurora, Colorado, United States

Site Status

Christiana Care Health System

Newark, Delaware, United States

Site Status

Moffitt Cancer Center

Tampa, Florida, United States

Site Status

Northwestern University

Chicago, Illinois, United States

Site Status

University of Chicago

Chicago, Illinois, United States

Site Status

Indiana University

Indianapolis, Indiana, United States

Site Status

University of Kansas

Westwood, Kansas, United States

Site Status

University of Louisville

Louisville, Kentucky, United States

Site Status

Louisiana State University - Health Sciences Center

New Orleans, Louisiana, United States

Site Status

University of Maryland

Baltimore, Maryland, United States

Site Status

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, United States

Site Status

Morristown Medical Center

Morristown, New Jersey, United States

Site Status

University of North Carolina

Chapel Hill, North Carolina, United States

Site Status

Providence Cancer Center Oncology and Hematology Care Clinic

Portland, Oregon, United States

Site Status

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, United States

Site Status

Avera Cancer Institute

Sioux Falls, South Dakota, United States

Site Status

University of Washington

Seattle, Washington, United States

Site Status

Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Site Status

Countries

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United States

References

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Ferris RL MD,, Leidner RS, Chung CH, Jimeno A, Lee SM, Sukari A, Nieva JJ, Grilley-Olson JE, Redman R, Wong SJ, Villaflor VM, Misleh J, Finckenstein FG, Chou J, Gastman B, Fiaz R, Catlett M, Yi M, Cohen EEW. Efficacy and safety of one-time autologous tumor-infiltrating lymphocyte cell therapy in patients with recurrent and/or metastatic head and neck squamous cell carcinoma. J Immunother Cancer. 2025 Aug 24;13(8):e011633. doi: 10.1136/jitc-2025-011633.

Reference Type DERIVED
PMID: 40854613 (View on PubMed)

Provided Documents

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Document Type: Study Protocol: Version 1

View Document

Document Type: Study Protocol: Version 2

View Document

Document Type: Study Protocol: Version 3

View Document

Document Type: Study Protocol: Version 4

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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2016-003446-86

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

C-145-03

Identifier Type: -

Identifier Source: org_study_id

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