Clinical Trials /

Autologous LN-145 in Patients With Metastatic Non-Small-Cell Lung Cancer

NCT04614103

Description:

This is a prospective, open-label, multi-cohort, non-randomized, multicenter phase 2 study evaluating LN-145 in patients with metastatic NSCLC.

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

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Autologous LN-145 in Patients With Metastatic Non-Small-Cell Lung Cancer
  • Official Title: A Phase 2 Multicenter Study of Autologous Tumor Infiltrating Lymphocytes (LN-145) in Patients With Metastatic Non-Small-Cell Lung Cancer

Clinical Trial IDs

  • ORG STUDY ID: IOV-LUN-202
  • SECONDARY ID: 2020-003629-45
  • NCT ID: NCT04614103

Conditions

  • Metastatic Non Small Cell Lung Cancer

Interventions

DrugSynonymsArms
LN-145TIL, Autologous Tumor Infiltrating LymphocytesCohort 1
LN-145TIL, Autologous Tumor Infiltrating LymphocytesCohort 3

Purpose

This is a prospective, open-label, multi-cohort, non-randomized, multicenter phase 2 study evaluating LN-145 in patients with metastatic NSCLC.

Detailed Description

      LN-145 is a ready-to-infuse, autologous TIL therapy that utilizes an autologous TIL
      manufacturing process, as originally developed by the NCI and further optimized by Iovance
      for the treatment of patients with metastatic NSCLC. The cell transfer therapy used in this
      study involves patients receiving an NMA lymphocyte depleting preparative regimen, followed
      by infusion of autologous TIL, then finally followed by the administration of IL-2.
    

Trial Arms

NameTypeDescriptionInterventions
Cohort 1ExperimentalPatients whose tumors did not express programmed cell death-ligand 1 (PD-L1) (tumor proportion score [TPS] < 1%) prior to their CPI treatment.
  • LN-145
Cohort 2ExperimentalPatients whose tumors expressed PD-L1 (TPS ≥ 1%) prior to their CPI treatment.
  • LN-145
Cohort 3ExperimentalPatients whose tumors do not express PD-L1 (TPS < 1%) prior to their CPI treatment and who are unable to safely undergo a surgical harvest for TIL generation due to at least one of the following: Unacceptable surgical risk Surgically approachable lesion is required for Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 assessment
  • LN-145
Cohort 4ExperimentalPatients who have been previously treated with LN-145 in Cohort 1, 2, or 3 of this study.
  • LN-145

Eligibility Criteria

        Inclusion Criteria:

          -  Confirmed histologic diagnosis of Non-Small-Cell Lung Carcinoma confirmation.

          -  Have received a single line of systemic therapy that included CPI and chemotherapy
             with documented radiographic disease progression on or following this single line of
             systemic therapy.

          -  LVEF > 45%, NYHA Class 1; cardiac stress test required

          -  FEV1>50% or FEV1/FVC>0.7 (6 min walk test if unable to perform or unreliable
             spirometry).

          -  At least 1 resectable lesion.

          -  Previously irradiated lesion must have radiographic progression prior to harvest.

          -  Must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1,
             and an estimated life expectancy of ≥ 6 months

          -  Patients of childbearing potential or those with partners of childbearing potential
             must be willing to practice an approved method of highly effective birth control
             during treatment and for 12 months after receiving all protocol-related therapy.

        Exclusion Criteria:

          -  Patients who have known oncogene driver mutations (eg, EGFR, ALK, ROS) which are
             sensitive to targeted therapies.

          -  Patients who have symptomatic and/or untreated brain metastases.

          -  Patients who have organ allograft or prior cell transfer within the past 20 years.

          -  Patients who are on systemic steroid therapy ≥ 10 mg/day of prednisone or other
             steroid equivalent. Patients receiving steroids as replacement therapy for
             adrenocortical insufficiency at ≤ 10 mg/day of prednisone or other steroid equivalent
             may be eligible.

          -  Patients who have any form of primary immunodeficiency

          -  Patients who have received a live or attenuated vaccination within 28 days prior to
             the start of treatment

          -  Patients who have had another primary malignancy within the previous 3 years

          -  Participation in another interventional clinical study within 21 days of the
             initiation of 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:Up to 60 months
Safety Issue:
Description:To evaluate the efficacy of LN-145 in patients with metastatic NSCLC without an actionable driver mutation who have disease progression on or following a single line of approved systemic therapy consisting of combined immune checkpoint inhibitor(s) (CPI[s]) + chemotherapy ± bevacizumab, as determined by objective response rate (ORR), using the RECIST v1.1, as assessed by the Independent Review Committee (IRC) (Cohorts 1 and 2) or by the Investigator (Cohorts 3 and 4)

Secondary Outcome Measures

Measure:Objective Response Rate
Time Frame:Up to 60 months
Safety Issue:
Description:To evaluate efficacy parameters such as Objective Response Rate (ORR) per RECIST v1.1
Measure:Complete Response Rate
Time Frame:Up to 60 months
Safety Issue:
Description:To evaluate efficacy parameters such as Complete Response Rate (CRR) per RECIST v1.1
Measure:Duration of Response
Time Frame:Up to 60 months
Safety Issue:
Description:To evaluate efficacy parameters such as Duration of Response (DOR) rate per RECIST v1.1
Measure:Disease Control Rate
Time Frame:Up to 60 months
Safety Issue:
Description:To evaluate efficacy parameters such as Disease Control Rate (DCR) per RECIST v1.1
Measure:Progression-Free Survival
Time Frame:Up to 60 months
Safety Issue:
Description:To evaluate efficacy parameters such as Progression-Free Survival (PFS) per RECIST v1.1
Measure:Overall Survival
Time Frame:Up to 60 months
Safety Issue:
Description:To evaluate efficacy parameters such as Overall Survival (OS)
Measure:Adverse Events
Time Frame:Up to 60 months
Safety Issue:
Description:To characterize the safety profile of LN-145 in NSCLC patients, as measured by the incidence of Grade ≥ 3 treatment-emergent adverse events (TEAEs)
Measure:Core Biopsies
Time Frame:Up to 60 months
Safety Issue:
Description:For Cohort 3 only: To evaluate the efficiency of generating LN-145 from tumor core biopsies; Percentage successful TIL products generated from core biopsies

Details

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

Trial Keywords

  • LN-145
  • Cell Therapy
  • Autologous Adoptive Cell Therapy
  • Cellular Immuno-therapy
  • Tumor Infiltrating Lymphocytes
  • TIL
  • IL-2
  • Non Small Cell Lung Cancer

Last Updated

November 19, 2020