Clinical Trials /

Study of Autologous Tumor Infiltrating Lymphocytes (LN-145) In Combo With Durvalumab in Non-Small Cell Lung Cancer

NCT03419559

Description:

This study is a Phase 2, open-label, multicenter study evaluating adoptive cell therapy (ACT) with autologous TIL therapy (LN-145) in combination with Anti-PD-L1 inhibitor durvalumab.

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Withdrawn

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Study of Autologous Tumor Infiltrating Lymphocytes (LN-145) Alone and In Combo With Durvalumab in Non-Small Cell Lung Cancer
  • Official Title: A Phase 2 Study to Assess the Efficacy and Safety of Autologous Tumor Infiltrating Lymphocytes (LN-145) Alone and In Combination With Anti-PD-L1 Inhibitor Durvalumab (MEDI4736) in Patients With Locally Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC)

Clinical Trial IDs

  • ORG STUDY ID: IOV-LUN-201
  • NCT ID: NCT03419559

Conditions

  • Non Small Cell Lung Cancer

Interventions

DrugSynonymsArms
LN-145Cohort 1 LN-145 alone
DurvalumabMEDI4736Cohort 2 LN-145 in combination with durvalumab

Purpose

This study is a Phase 2, open-label, 2-cohort, multicenter study evaluating adoptive cell therapy (ACT) with autologous TIL therapy (LN-145) alone, (Cohort 1), or in combination with durvalumab (anti-programmed cell death ligand 1 [PD-L1] monoclonal antibody [mAb]) (Cohort 2).

Detailed Description

      LN-145 is an adoptive cell transfer therapy that utilizes an autologous TIL manufacturing
      process, as originally developed by the NCI. The cell transfer therapy used in this study
      involves patients receiving a nonmyeloablative (NMA) lymphocyte depleting preparative
      regimen, followed by infusion of autologous TIL followed by the administration of up to 6
      doses of IL-2. Patients in Cohort 2 will also receive durvalumab Q4Weeks until progression or
      unacceptable toxicity.
    

Trial Arms

NameTypeDescriptionInterventions
Cohort 1 LN-145 aloneExperimentalAfter nonmyeloablative (NMA) lymphodepletion, patients are infused with their autologous (LN-145) followed by IL-2 administration
    Cohort 2 LN-145 in combination with durvalumabActive ComparatorAfter nonmyeloablative (NMA) lymphodepletion, patients are infused with their autologous (LN-145) followed by IL-2 administration. Patients in cohort 2 will also receive durvalumab Q4Weeks
    • Durvalumab

    Eligibility Criteria

            Inclusion Criteria:
    
              -  Confirmed diagnosis of Stage III or Stage IV NSCLC and have received ≥ 1 line of prior
                 systemic therapy in the locally advanced or metastatic setting
    
              -  Have at least 1 resectable lesion to generate TIL
    
              -  Measurable disease as defined by Response Evaluation Criteria in Solid Tumors, version
                 1.1 (RECIST 1.1)
    
              -  Male or female, ≥ 18 years of age
    
              -  Body weight > 30 kg
    
              -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, and estimated
                 life expectancy of ≥ 3 months
    
              -  Adequate bone marrow function at screening
    
              -  Adequate organ function at screening
    
              -  If the patient is of childbearing potential or their partner(s) is of childbearing
                 potential, they must agree to use highly effective method of contraception while on
                 study and for 6 months after receiving all protocol-related therapy.
    
            Exclusion Criteria:
    
              -  Must not have a history of other malignancies, except for adequately treated
                 nonmelanoma skin cancer, curatively treated in-situ cancer of the cervix,
                 curatively-treated thyroid cancer, or other solid tumors curatively treated with no
                 evidence of disease for ≥ 3 years
    
              -  Patients may not have received prior cell therapy
    
              -  Patients may not have received prior anti PD-1 or anti PD-L1 inhibitors
    
              -  Active or prior documented autoimmune or inflammatory disorders
    
              -  History of primary immunodeficiency, history of allogeneic organ transplant that
                 requires therapeutic immunosuppression
    
              -  Received live or attenuated vaccination within 28 days prior to the start of NMA-LD
    
              -  History of hypersensitivity to cyclophosphamide, fludarabine, dimethyl sulfoxide
                 (DMSO) or IL-2
    
              -  Known allergic reaction to antibiotics of the aminoglycoside group (ie, streptomycin,
                 gentamicin)
    
              -  Mean QT interval ≥ 470 msec
    
              -  Decreased cardiac function as evidenced by a left ventricular ejection fraction of <
                 45%
    
              -  Uncontrolled intercurrent illness
    
              -  Patients who have obstructive or restrictive pulmonary disease and have a documented
                 FEV1 (forced expiratory volume in 1 second) of ≤ 60%
    
              -  Active central nervous system metastases and/or leptomeningeal disease
    
              -  Current or prior use of immunosuppressive medication within 28 days before the first
                 study treatment
          
    Maximum Eligible Age:N/A
    Minimum Eligible Age:18 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Objective response rate
    Time Frame:A maximum of 24 months
    Safety Issue:
    Description:To evaluate efficacy using the objective response rate (ORR

    Secondary Outcome Measures

    Measure:Duration of Response
    Time Frame:A maximum of 24 months
    Safety Issue:
    Description:To further evaluate efficacy such as the duration of response (DOR)
    Measure:Progression-free Survival
    Time Frame:A maximum of 24 months
    Safety Issue:
    Description:To further evaluate efficacy such as progression free survival (PFS) (PFS)
    Measure:Overall Survival
    Time Frame:A minimum of 3 years
    Safety Issue:
    Description:To further evaluate efficacy such as overall survival (OS)

    Details

    Phase:Phase 2
    Primary Purpose:Interventional
    Overall Status:Recruiting
    Lead Sponsor:Iovance Biotherapeutics, Inc.

    Trial Keywords

    • LN-145
    • Cell Therapy
    • Autologous Adoptive Cell Transfer
    • Cellular Immuno-therapy
    • TIL
    • IL-2
    • Durvalumab

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