Clinical Trials /

Study of Autologous Tumor Infiltrating Lymphocytes in Patients With Solid Tumors

NCT03645928

Description:

A prospective, open-label, multi-cohort, non-randomized, multicenter Phase 2 study evaluating adoptive cell therapy (ACT) with TIL LN-144 (Lifileucel)/LN-145 in combination with pembrolizumab. TIL as a single-therapy will be evaluated with LN-145 only.

Related Conditions:
  • Head and Neck Squamous Cell Carcinoma
  • Metastatic Melanoma
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Study of Autologous Tumor Infiltrating Lymphocytes in Patients With Solid Tumors
  • Official Title: A Phase 2, Multicenter Study of Autologous Tumor Infiltrating Lymphocytes (LN 144 or LN-145) in Patients With Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: IOV-COM-202
  • SECONDARY ID: 2018-001608-12
  • NCT ID: NCT03645928

Conditions

  • Metastatic Melanoma
  • Squamous Cell Carcinoma of the Head and Neck
  • Non-small Cell Lung Cancer

Interventions

DrugSynonymsArms
LifileucelLN-144Cohort 1A
LN-145TIL, autologous tumor infiltrating lymphocytesCohort 2A
PembrolizumabCohort 1A

Purpose

A prospective, open-label, multi-cohort, non-randomized, multicenter Phase 2 study evaluating adoptive cell therapy (ACT) with TIL LN-144 (Lifileucel)/LN-145 in combination with pembrolizumab. TIL as a single-therapy will be evaluated with LN-145 only.

Detailed Description

      LN-144 (Lifileucel)/LN-145 is an adoptive cell transfer therapy that utilizes an autologous
      TIL manufacturing process for the treatment of patients with advanced unresectable or
      metastatic melanoma, advanced squamous cell carcinoma of the head and neck, and non-small
      cell lung cancer. The adoptive 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. Patients in
      Cohort 1A, Cohort 2A, and Cohort 3A will receive TIL plus pembrolizumab. Patients in Cohort
      3B will receive TIL as a single therapy.
    

Trial Arms

NameTypeDescriptionInterventions
Cohort 1AExperimentalLifileucel (LN-144) therapy in combination with pembrolizumab in patients with advanced unresectable or metastatic melanoma, who have not received prior immunotherapy including checkpoint inhibitors (eg, anti-PD-1/anti-PD-L1, anti-CTLA-4).
  • Lifileucel
  • Pembrolizumab
Cohort 2AExperimentalTIL LN-145 therapy in combination with pembrolizumab in patients with advanced HNSCC, who have not received prior immunotherapy including checkpoint inhibitors (eg, anti-PD-1/anti-PD-L1).
  • LN-145
  • Pembrolizumab
Cohort 3AExperimentalTIL LN-145 therapy in combination with pembrolizumab in patients with locally advanced or metastatic (Stage III-IV) non-small-cell lung cancer (NSCLC) with ≤ 3 prior lines of systemic therapy, excluding immunotherapy.
  • LN-145
  • Pembrolizumab
Cohort 3BExperimentalTIL LN-145 therapy as a single agent in NSCLC, who have previously received systemic therapy with checkpoint inhibitors (eg, anti-PD-1/anti-PD-L1) as part of at least one of their 1-3 lines of prior systemic therapy.
  • LN-145

Eligibility Criteria

        Inclusion Criteria

          -  Must have a confirmed diagnosis of malignancy of their receptive histologies:
             unresectable or metastatic melanoma (Cohort 1A), advanced recurrent or metastatic
             squamous cell carcinoma of the head and neck (Cohort 2A), or Stage III or Stage IV
             non-small cell lung cancer (Cohorts 3A and 3B).

          -  Cohorts 1A, 2A, and 3A only: If previously treated, patients must have progressed on
             or after most recent therapy. Cohorts 1A, 2A, and 3A may have received up to 3 prior
             systemic anticancer therapies

          -  Cohort 3B only: Patients with Stage III or Stage IV NSCLC who have previously received
             systemic therapy with CPIs (eg, anti-PD-1/anti-PD-L1) as part of ≤ 3 prior lines of
             systemic therapy. Patients must have radiographically confirmed progression on or
             after most recent therapy.

          -  Must have at least 1 resectable lesion

          -  Must have a remaining measurable disease as defined by RECIST 1.1 following tumor
             resection

          -  Must be ≥18 years at the time of consent.

          -  Must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1,
             and an estimated life expectancy of ≥ 3 months

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

        Exclusion Criteria

          -  Patients with melanoma of uveal/ocular origin.

          -  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.

          -  Patients with symptomatic and/or untreated brain metastases

          -  Patients who are on a systemic steroid therapy within 21 days of enrollment.

          -  Patients who are pregnant or breastfeeding.

          -  Patients who have an active medical illness(es), which in the opinion of the
             Investigator, would pose increased risks for study participation

          -  Patients may not have active or prior documented autoimmune or inflammatory disorders

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

          -  Patients who have any form of primary immunodeficiency

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

          -  Patients who have a left ventricular ejection fraction (LVEF) > 45% or who are New
             York Heart Association Class II or higher

          -  Patients who have obstructive or restrictive pulmonary disease and have a documented
             FEV1 ≤ 60% of predicted normal

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

          -  Participation in another clinical study with an investigational product 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 autologous TIL LN-144 (Lifileucel)/LN-145 in combination with pembrolizumab in MM, HNSCC, or NSCLC patients or TIL LN-145 as a single therapy in relapsed or refractory (r/r) NSCLC patients, who have previously progressed on or after treatment with CPIs, as determined by objective response rate (ORR), using the Response Evaluation Criteria in Solid Tumors (RECIST 1.1), as assessed by Investigator.

Secondary Outcome Measures

Measure:Complete Response Rate
Time Frame:Up to 60 months
Safety Issue:
Description:To evaluate efficacy parameters such Complete Response (CR) rate per RECIST 1.1, as assessed by the Investigator
Measure:Duration of Response
Time Frame:Up to 60 months
Safety Issue:
Description:To evaluate efficacy parameters such Duration of Response (DOR) per RECIST 1.1, as assessed by the Investigator
Measure:Disease Control Rate
Time Frame:Up to 60 months
Safety Issue:
Description:To evaluate efficacy parameters such Disease Control Rate (DCR) per RECIST 1.1, as assessed by the Investigator
Measure:Progression-Free Survival
Time Frame:Up to 60 months
Safety Issue:
Description:To evaluate efficacy parameters such Progression-Free Survival (PFS) per RECIST 1.1, as assessed by the Investigator
Measure:Overall Survival
Time Frame:Up to 60 months
Safety Issue:
Description:To evaluate efficacy parameters such Overall Survival (OS)

Details

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

Trial Keywords

  • LN-144
  • LN-145
  • Cell Therapy
  • Autologous Adoptive Cell Transfer
  • Autologous Adoptive Cell Therapy
  • Cellular Immuno-therapy
  • Tumor Infiltrating Lymphocytes
  • TIL
  • IL-2
  • Multiple Tumor Type
  • Lifileucel
  • Pembrolizumab

Last Updated

December 17, 2019