Study of LN-145/LN-145-S1 Autologous Tumor Infiltrating Lymphocytes in the Treatment of Squamous Cell Carcinoma of the Head & Neck
Condition: Squamous Cell Carcinoma of the Head and Neck
MeSH terms: Carcinoma; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck
Intervention: LN-145; LN-145-S1
Intervention description: 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.; 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.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 64.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
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

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
    

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.