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Clinical Trial 18944

Cancer Type: Head & Neck
Study Type: Treatment
NCT#: NCT03083873

Phase: Phase II
Prinicipal Investigator:

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Overview

Study Title

A Phase 2 Study to Evaluate the Safety, Tolerability and Efficacy of Cell Transfer Therapy Using Autologous Tumor Infiltrating Lymphocytes (LN-145) followed by IL-2 in Patients with Recurrent and/or Metastatic Squamous Cell Carcinoma of the Head and Neck

Summary

The purpose of this study is to find out if an investigational product called LN-145 is safe to give to participants with recurrent and/or metastatic head and neck cancer and if processing tumors to obtain cells in a central lab works.

Objective

Primary Objectives: - To evaluate the safety and tolerability of lymphodepletion, LN-145, and IL-2 in patients with recurrent and/or metastatic HNSCC. - To evaluate the efficacy of therapy using the overall response rate (ORR) in patients with recurrent and/or metastatic HNSCC. Secondary Objectives: - To evaluate other efficacy parameters such as complete response (CR) rate, the duration of response (DOR), progression-free survival (PFS), and overall survival (OS) in patients with recurrent and/or metastatic HNSCC. Exploratory Objectives: - To explore persistence of TILs and immune correlates of response, survival, toxicity of the treatment.

Treatments

Therapies

Medications

IL-2 (Interleukin-2); LN-145 (); LN-145-S1 (); MESNA (); TIL (); cyclophosphamide (); cytoxan (cyclophosphamide); fludarabine (Fludarabine phosphate)

Inclusion Criteria

Inclusion Criteria:

  • Must be 18 years of age or older at the time of consent. Enrollment of patients over 70 years of age may be allowed after consultation with the Medical Monitor.
  • Patient (or a legally authorized representative) must understand and voluntarily sign informed consent prior to any study-related assessments/procedures being conducted.
  • Must be able and willing to comply to the study visit schedule and protocol requirements.
  • Must have recurrent and/or metastatic HNSCC. Histologic diagnosis of the primary tumor is required via the pathology report.
  • Must have at least 1 lesion that is resectable for TIL generation. The resected TIL- generating lesion should yield at least 1.5 cm in diameter post-resection of tumor tissue and can be surgically removed with minimal morbidity. An aggregate of ≥ 1.5 cm in diameter from multiple lesions is permitted. If the lesion is within a previously irradiated field, the irradiation must have occurred at least 3 months prior to resection and the lesion must have had radiologically documented progression after radiation therapy.
  • Must have measurable disease as defined by RECIST v1.1 following the tumor resection for TIL manufacturing. Lesions in previously irradiated areas must not be selected as target lesions unless there has been demonstrated radiographic progression in those lesions. Lesions that are partially resected for TIL generation and are still measurable per RECIST may be selected as non-target lesions but cannot serve as a target lesion for response assessment.
  • Must have received at least 1 and no more than 3 lines of prior systemic immunotherapy and/or chemotherapeutic treatments for HNSCC. Patients must have radiologically documented disease progression while receiving or after completion of the most recent prior treatment. Prior systemic therapy in the adjuvant or neoadjuvant setting, or as part of definitive chemoradiotherapy, will be counted as a line of therapy if the disease progressed during or within 12 months of the completion of such therapy.
  • Any prior therapy directed at the malignant tumor, including chemotherapy, biologic/targeted agents, and immunologic agents must be discontinued at least 28 days prior to lymphodepletion except for localized palliative radiation therapy.
  • Must meet the laboratory criteria independent of transfusion and/or blood product support for at least 5 days prior to laboratory testing as outlined per protocol.
  • Patients must be seronegative for the human immunodeficiency virus (HIV1 and HIV2).
  • Patients seropositive for hepatitis B 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. Additional serology testing may be required depending on local prevalence of certain viral exposures.
  • Patients of childbearing potential and patients whose sexual partners are of childbearing potential must be willing to practice an approved method of highly effective must be willing to practice an approved method of birth control with their partners; starting at the time of informed consent and for 1 year after the completion of the study treatment regimen. Approved methods of birth control as indicated in protocol.
  • Pulmonary function requirement outlined in protocol.

  • Exclusion Criteria

    Exclusion Criteria:

  • Patients who have received an organ allograft or prior cell transfer therapy that included a nonmyeloablative or myeloablative chemotherapy regimen within the past 20 years. Note: This criterion is applicable for patients undergoing retreatment with TIL with the exception that they will have had a prior NMA-LD regimen with their prior TIL treatment.
  • Patients who are on a systemic steroid therapy > 10 mg of prednisone or other steroid equivalent daily. Patients receiving steroids as replacement therapy for adrenocortical insufficiency are study eligible.
  • Patients with prior therapy-related toxicities Grade >1 per NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03; (see Appendix 17.4), except for neuropathy, dysphagia, alopecia, or vitiligo. Immunotherapy-related endocrinopathies stable for at least 1 month, and controlled with hormonal replacement, are not excluded. If toxicities have resolved to Grade > Patients with documented Grade ≥2 diarrhea or colitis due to previous immunotherapy (eg, ipilimumab, tremelimumab, anti-PD-1, or anti-PD-L1) within 6 months from screening. Patients who had a normal colonoscopy post anti-PD-1/anti-PD-L1 treatment with uninflamed mucosa by visual assessment, or who have been asymptomatic for ≥6 months, are not excluded
  • Patients who have a contraindication to or history of hypersensitivity reaction to any component or excipients of the TIL therapy and other study drugs: NMA-LD (cyclophosphamide, mesna, and fludarabine), IL-2, Antibiotics of the aminoglycosides group (ie, gentamicin or streptomycin; excluding those who are skin-test negative for gentamicin hypersensitivity), Any component of the TIL infusion product formulation including dimethyl sulfoxide (DMSO), human serum albumin (HSA), IL-2, and dextran-40
  • Patients with active systemic infections (eg, syphilis), coagulation disorders, or other active major medical illnesses of the cardiovascular, respiratory, or immune system; including evidence in the medical history of a positive cardiac stress test, myocardial infarction, cardiac arrhythmia, obstructive or restrictive pulmonary disease, uveitis, or other conditions, that in the opinion of the Investigator, would significantly increase the risk of participation.
  • Patients with symptomatic and/or untreated brain metastases (of any size and any number). Patients with definitively treated brain metastases may be considered eligible after discussion with the Sponsor’s Medical Monitor/designee, must be stable for at least 2 weeks and must be asymptomatic prior to the start of treatment (NMA-LD)
  • Patients who 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) > Patients who have had another primary malignancy within the previous 3 years (some exceptions apply)
  • Additional exclusions apply

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