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

Study Overview
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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.

Official Title
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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

Conditions
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Squamous Cell Carcinoma of the Head and Neck

Intervention / Treatment
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* Biological: LN-145
* Biological: LN-145-S1


Participation Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>Treatment with LN-145, Generation 1 (Gen 1), non-cryopreserved TIL | Biological: LN-145<br>* 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.<br>* Other names: TIL, autologous tumor infiltrating lymphocytes;|
| Experimental: Cohort 2<br>Treatment with LN-145 Generation 2 (Gen 2), cryopreserved TIL | Biological: LN-145<br>* 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.<br>* Other names: TIL, autologous tumor infiltrating lymphocytes;|
| Experimental: Cohort 3<br>Treatment with LN-145 Generation 3 (Gen 3), cryopreserved TIL | Biological: LN-145<br>* 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.<br>* Other names: TIL, autologous tumor infiltrating lymphocytes;|
| Experimental: Cohort 4<br>Treatment with LN-145-S1 cryopreserved TIL | Biological: LN-145-S1<br>* 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.<br>* Other names: TIL, autologous tumor infiltrating lymphocytes;|
| Experimental: Cohort 5<br>LN-145 cryopreserved/LN-145-S1 cryopreserved TIL re-treatment | Biological: LN-145<br>* 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.<br>* Other names: TIL, autologous tumor infiltrating lymphocytes;Biological: LN-145-S1<br>* 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.<br>* Other names: TIL, autologous tumor infiltrating lymphocytes;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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LN-145, Cell Therapy, Autologous Adoptive Cell Transfer, Autologous Adoptive Cell Therapy, Cellular Immuno-therapy, Tumor Infiltrating Lymphocytes, TIL, IL-2, LN-145-S1