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Withdrawn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) 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) 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-145TIL, autologous tumor infiltrating lymphocytesLN-145 in combination with durvalumab
DurvalumabMEDI4736LN-145 in combination with durvalumab

Purpose

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.

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 a regimen
      of IL-2.
    

Trial Arms

NameTypeDescriptionInterventions
LN-145 in combination with durvalumabExperimentalAfter nonmyeloablative (NMA) lymphodepletion, patients are infused with their autologous TIL (LN-145) followed by IL-2 administration.
  • LN-145
  • Durvalumab

Eligibility Criteria

        Inclusion Criteria:

          -  Confirmed diagnosis of Stage III or Stage IV NSCLC and progressed after ≤ 3 lines of
             prior systemic therapy in the locally advanced or metastatic setting

          -  Have at least 1 lesion resectable for TIL generation

          -  Measurable disease as defined by RECIST v1.1

          -  Male or female, ≥ 18 years of age

          -  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

          -  A washout period from prior anticancer therapy(ies) of a minimum duration is required
             prior to first study treatment

          -  Recovered from all prior anticancer therapy-related AEs to Grade 1 or less (per CTCAE
             v4.03) prior to enrollment

          -  Female patients of childbearing potential and male patients with partners of
             childbearing potential patient must agree to use contraception while on study and
             during the timeframes as specified following the last dose of study drug(s) received,
             or until the first dose of the subsequent anticancer therapy, whichever is longer

          -  Evidence of postmenopausal status or negative urine or serum pregnancy test for female
             premenopausal patients

        Exclusion Criteria:

          -  History of other malignancies, except for the following: 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 who have received prior cell therapy

          -  Patients who have received prior checkpoint inhibitors: such as anti-PD-1, anti-PD-L1
             inhibitors, and durvalumab

          -  Active or prior documented autoimmune or inflammatory disorders

          -  History of primary or acquired immunodeficiency syndrome, history of allogeneic organ
             transplant that requires therapeutic immunosuppression

          -  Received live or attenuated vaccination within 28 days prior to the start of NMA-LD

          -  Patients with a history of hypersensitivity to any component of the study drugs

          -  Mean QT interval ≥ 470 msec

          -  Patients who have a left ventricular ejection fraction (LVEF) of < 45% or who are New
             York Heart Association (NYHA) Class 2 or higher

          -  Serious illnesses or medical conditions, which would pose increased risk for study
             participation and/or compliance with the protocol

          -  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

          -  Female patients who are pregnant or breastfeeding

          -  Active infection including tuberculosis (TB), hepatitis B, hepatitis C, or HIV

          -  Current or prior use of immunosuppressive medication within 28 days before the first
             dose of study treatment, with the exceptions of intranasal and inhaled corticosteroids
             or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day
             of prednisone, or an equivalent corticosteroid
      
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)
Measure:Overall Survival
Time Frame:A minimum of 5 years
Safety Issue:
Description:To further evaluate efficacy such as overall survival (OS)

Details

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

Trial Keywords

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

Last Updated

April 16, 2019