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

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

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

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.

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.