Clinical trial NCT03083873: Study of LN-145/LN-145-S1 Autologous Tumor Infiltrating Lymphocytes in the Treatment of Squamous Cell Carcinoma of the Head & Neck
Official title: A Phase 2, Multicenter Study to Evaluate the Efficacy and Safety of Autologous Tumor Infiltrating Lymphocytes (LN-145/LN-145-S1) for the Treatment of Patients With Recurrent and/or Metastatic Squamous Cell Carcinoma of the Head and Neck
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Squamous Cell Carcinoma of the Head and Neck
Keywords: LN-145
Cell Therapy
Autologous Adoptive Cell Transfer
Autologous Adoptive Cell Therapy
Cellular Immuno-therapy
Tumor Infiltrating Lymphocytes
TIL
IL-2
LN-145-S1
Lead sponsor: Iovance Biotherapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2017-03-20
Enrollment: 64
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Objective Response Rate
timeFrame: Up to 24 months
Secondary outcomes:
measure: Duration of Response
timeFrame: Up to 24 months
measure: Disease Control Rate
timeFrame: Up to 24 months
measure: Progression-Free Survival
timeFrame: Up to 24 months
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama
state: Alabama
city: La Jolla
country: United States
facility: University of California San Diego
state: California
city: Los Angeles
country: United States
facility: University of California, Los Angeles
state: California
city: Los Angeles
country: United States
facility: University of Southern California
state: California
city: Aurora
country: United States
facility: University of Colorado
state: Colorado
city: Newark
country: United States
facility: Christiana Care Health System
state: Delaware
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
city: Westwood
country: United States
facility: University of Kansas
state: Kansas
city: Louisville
country: United States
facility: University of Louisville
state: Kentucky
city: New Orleans
country: United States
facility: Louisiana State University - Health Sciences Center
state: Louisiana
city: Baltimore
country: United States
facility: University of Maryland
state: Maryland
city: Detroit
country: United States
facility: Barbara Ann Karmanos Cancer Institute
state: Michigan
city: Morristown
country: United States
facility: Morristown Medical Center
state: New Jersey
city: Chapel Hill
country: United States
facility: University of North Carolina
state: North Carolina
city: Portland
country: United States
facility: Providence Cancer Center Oncology and Hematology Care Clinic
state: Oregon
city: Pittsburgh
country: United States
facility: UPMC Hillman Cancer Center
state: Pennsylvania
city: Sioux Falls
country: United States
facility: Avera Cancer Institute
state: South Dakota
city: Seattle
country: United States
facility: University of Washington
state: Washington
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
Study officials:
affiliation: Iovance Biotherapeutics
name: Iovance Biotherapeutics Medical Monitor
role: STUDY_DIRECTOR
References: