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 or TIL LN-145/LN-145-S1 as a single therapy.

Related Conditions:
  • Head and Neck Squamous Cell Carcinoma
  • 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/LN-145/LN-145-S1) 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-144, TIL, autologous tumor infiltrating lymphocytes, lifileucelCohort 1A
LN-145TIL, autologous tumor infiltrating lymphocytesCohort 2A
PembrolizumabCohort 1A
LN-145-S1TIL, autologous tumor infiltrating lymphocytesCohort 1B

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 or TIL LN-145/LN-145-S1 as a single therapy.

Detailed Description

      LN-144 (Lifileucel)/LN-145/LN-145-S1 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) lymphodepletion regimen, followed by infusion of
      autologous TIL followed by the administration of a regimen of IL-2. Patients in Cohorts 1A,
      Cohort 2A, and Cohort 3A will receive TIL plus pembrolizumab. Patients in Cohorts 1B and
      Cohort 3B will receive TIL as a single therapy.
    

Trial Arms

NameTypeDescriptionInterventions
Cohort 1AExperimentalTIL LN-144 therapy in combination with pembrolizumab in patients with Stage IIIC or Stage IV unresectable or metastatic melanoma (MM) with ≤ 3 prior lines of systemic therapy, excluding immune checkpoint inhibitor (CPI) therapy.
  • Lifileucel
  • Pembrolizumab
Cohort 1BExperimentalTIL LN-145-S1 therapy as a single agent in patients with Stage IIIC or Stage IV unresectable or MM, who have previously received systemic therapy with a PD-1 blocking antibody as at least one of their 1-3 lines of prior systemic therapy. If the tumor is proto-oncogene B-Raf (BRAF) V600 mutation positive, patients must have received a BRAF inhibitor or BRAF inhibitor in combination with a mitogen-activated extracellular signal-related kinase (MEK) inhibitor.
  • LN-145-S1
Cohort 2AExperimentalTIL LN-145 therapy in combination with pembrolizumab in patients with advanced, recurrent, or metastatic HNSCC, with ≤ 3 prior lines of systemic therapy, excluding CPIs.
  • 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 CPIs.
  • LN-145
  • Pembrolizumab
Cohort 3BExperimentalTIL LN-145 therapy as a single agent in NSCLC, (Stage III-IV), 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 Stage IIIC or Stage IV (Cohorts 1A and 1B),
             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: Patients must be CPI naive. If previously treated,
             patients must have progressed on or after most recent therapy and must not have
             received CPIs as part of one of the counted lines of prior therapy. Patients must have
             radiologically documented disease progression while receiving or after the completion
             of the most recent prior treatment. Cohorts 1A, 2A, and 3A may have received up to 3
             prior systemic anticancer therapies

          -  Cohorts 1B and 3B: Patients must have previously received systemic therapy with PD-1
             blocking antibody for MM or any CPI for NSCLC as part of ≤ 3 prior lines of therapy.
             Patients must have radiologically documented disease progression while receiving or
             after the completion of the most recent prior treatment.

          -  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 for Cohorts 1A, 2A, 3A, and 3B. Patients must
             be ≥ 12 years at the time of consent for Cohort 1B. Enrollment of patients > 70 years
             of age may be allowed after consultation with the Medical Monitor.

          -  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 birth control during treatment and
             for 12 months after receiving 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 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 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

          -  Pulmonary function requirement - Patients having any of the following require
             pulmonary function testing (PFT) with post-bronchodilator values of forced expiratory
             volume (FEV1)/forced vital capacity (FVC) > 0.7 and FEV1 > 50%: History of cigarette
             smoking of ≥ 20 pack-years and still smoking, ceased smoking within the past 2 years,
             history of chronic obstructive pulmonary disease (COPD), any signs or symptoms of
             respiratory dysfunction

          -  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:12 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 NSCLC patients and TIL LN-145-S1 in MM patients (who have previously progressed on or after treatment with a PD-1 blocking antibody for MM or any CPI for NSCLC), 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
  • LN-145-S1

Last Updated

February 26, 2020