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

Phase 2

Completed

• Conditions: Squamous Cell Carcinoma of the Head and Neck
• Interventions: Biological: LN-145; Biological: LN-145-S1

• Registration Number: NCT03083873
• Lead Sponsor: Iovance Biotherapeutics, Inc.

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.

Study Timeline

• Study Start: 2017-01-09
• Study First Submitted: 2017-03-14
• Study First Submitted QC: 2017-03-14
• Study First Posted: 2017-03-20
• Primary Completion: 2022-08-08
• Study Completion: 2022-08-08
• Results First Submitted: 2023-08-04
• Status Verified: 2023-09
• Results First Submitted QC: 2023-09-21
• Last Update Submitted: 2023-09-21
• Results First Posted: 2023-10-12
• Last Update Posted: 2023-10-12

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 64

Inclusion Criteria

Not provided

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Cohort 1	LN-145	Treatment with LN-145, Generation 1 (Gen 1), non-cryopreserved TIL
Cohort 3	LN-145	Treatment with LN-145 Generation 3 (Gen 3), cryopreserved TIL
Cohort 5	LN-145	LN-145 cryopreserved/LN-145-S1 cryopreserved TIL re-treatment
Cohort 2	LN-145	Treatment with LN-145 Generation 2 (Gen 2), cryopreserved TIL
Cohort 4	LN-145-S1	Treatment with LN-145-S1 cryopreserved TIL
Cohort 5	LN-145-S1	LN-145 cryopreserved/LN-145-S1 cryopreserved TIL re-treatment

Primary Outcome Measures

Name	Time	Method
Objective Response Rate	Up to 24 months	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.

Secondary Outcome Measures

Name	Time	Method
Duration of Response	Up to 24 months	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.
Disease Control Rate	Up to 24 months	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.
Progression-Free Survival	Up to 24 months	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.

Trial Locations

Locations (22)

University of Southern California; 🇺🇸 Los Angeles, California, United States

Northwestern University; 🇺🇸 Chicago, Illinois, United States

University of California, Los Angeles; 🇺🇸 Los Angeles, California, United States

University of Chicago; 🇺🇸 Chicago, Illinois, United States

Indiana University; 🇺🇸 Indianapolis, Indiana, United States

University of Kansas; 🇺🇸 Westwood, Kansas, United States

University of Maryland; 🇺🇸 Baltimore, Maryland, United States

Barbara Ann Karmanos Cancer Institute; 🇺🇸 Detroit, Michigan, United States

UPMC Hillman Cancer Center; 🇺🇸 Pittsburgh, Pennsylvania, United States

University of Washington; 🇺🇸 Seattle, Washington, United States

University of Colorado; 🇺🇸 Aurora, Colorado, United States

Moffitt Cancer Center; 🇺🇸 Tampa, Florida, United States

Medical College of Wisconsin; 🇺🇸 Milwaukee, Wisconsin, United States

University of Alabama; 🇺🇸 Birmingham, Alabama, United States

University of California San Diego; 🇺🇸 La Jolla, California, United States

Christiana Care Health System; 🇺🇸 Newark, Delaware, United States

Louisiana State University - Health Sciences Center; 🇺🇸 New Orleans, Louisiana, United States

Providence Cancer Center Oncology and Hematology Care Clinic; 🇺🇸 Portland, Oregon, United States

Morristown Medical Center; 🇺🇸 Morristown, New Jersey, United States

Avera Cancer Institute; 🇺🇸 Sioux Falls, South Dakota, United States

University of Louisville; 🇺🇸 Louisville, Kentucky, United States

University of North Carolina; 🇺🇸 Chapel Hill, North Carolina, United States