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

Squamous Cell Carcinoma of the Head and Neck Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03083873
• Other study ID #: C-145-03
• Secondary ID: 2016-003446-86
• Status: Completed
• Phase: Phase 2
• Start date: January 9, 2017
• Est. completion date: August 8, 2022

Study information

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

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 64
• Est. completion date: August 8, 2022
• Est. primary completion date: August 8, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Squamous Cell
• Squamous Cell Carcinoma of Head and Neck
• Squamous Cell Carcinoma of the Head and Neck

Intervention

Biological:
• 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.
• 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.

Locations

Country	Name	City	State
United States	University of Colorado	Aurora	Colorado
United States	University of Maryland	Baltimore	Maryland
United States	University of Alabama	Birmingham	Alabama
United States	University of North Carolina	Chapel Hill	North Carolina
United States	Northwestern University	Chicago	Illinois
United States	University of Chicago	Chicago	Illinois
United States	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan
United States	Indiana University	Indianapolis	Indiana
United States	University of California San Diego	La Jolla	California
United States	University of California, Los Angeles	Los Angeles	California
United States	University of Southern California	Los Angeles	California
United States	University of Louisville	Louisville	Kentucky
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Morristown Medical Center	Morristown	New Jersey
United States	Louisiana State University - Health Sciences Center	New Orleans	Louisiana
United States	Christiana Care Health System	Newark	Delaware
United States	UPMC Hillman Cancer Center	Pittsburgh	Pennsylvania
United States	Providence Cancer Center Oncology and Hematology Care Clinic	Portland	Oregon
United States	University of Washington	Seattle	Washington
United States	Avera Cancer Institute	Sioux Falls	South Dakota
United States	Moffitt Cancer Center	Tampa	Florida
United States	University of Kansas	Westwood	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
Iovance Biotherapeutics, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective Response Rate	The percentage of patients who have a confirmed complete response or partial response as assessed by the investigator per RECIST v1.1. Objective response rate (ORR) will be defined as the percentage of the patients with a confirmed complete or partial response (CR or PR),by MRI or CT scan as per RECIST 1.1 criteria.; Complete response (CR), Disappearance of all target and non-target lesions. All lymph nodes must be non-pathological in size(<10mm short axis). No new lesions.; Partial response (PR), At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Persistence of one or more non-target lesion(s) and/or maintenance above the normal limits (Non-CR/Non-PD). No new lesions.	Up to 24 months
Secondary	Duration of Response	To evaluate efficacy parameters such as Duration of Response (DOR) using RECIST v1.1 as assessed by the Investigator. DOR is measured from the time point at which the initial measurement criteria per RECIST v1.1 are met for a CR or PR (if response is a confirmed response), whichever response is observed first, until PD.	Up to 24 months
Secondary	Disease Control Rate	The percentage of patients who have a best overall response of complete response, partial response, or stable disease as assessed by the investigator per RECIST v1.1. The BOR of SD must be at least 4 weeks from LN-145/LN-145-S1 infusion.	Up to 24 months
Secondary	Progression-Free Survival	The time (in months) from the date of the TIL infusion to progressive disease as assessed by the Investigator using RECIST v1.1 or death due to any cause, whichever occurs earlier. Progression was defined using Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.1) as at least a 20% increase in the sum of diameters of the target lesions and an absolute increase of at least 5 mm, and/or unequivocal progression of existing non-target lesions, and/or the appearance of 1 or more new lesions.	Up to 24 months