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Study of Autologous Tumor Infiltrating Lymphocytes in Patients With Solid Tumors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03645928
Recruitment Status : Recruiting
First Posted : August 24, 2018
Last Update Posted : September 11, 2020
Sponsor:
Information provided by (Responsible Party):
Iovance Biotherapeutics, Inc.

Tracking Information
First Submitted Date  ICMJE August 22, 2018
First Posted Date  ICMJE August 24, 2018
Last Update Posted Date September 11, 2020
Actual Study Start Date  ICMJE May 7, 2019
Estimated Primary Completion Date December 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 14, 2020)
  • Objective Response Rate [ Time Frame: Up to 60 months ]
    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), as determined by objective response rate (ORR), using the Response Evaluation Criteria in Solid Tumors (RECIST 1.1), as assessed by Investigator.
  • Safety Profile Measured by Grade ≥3 TEAEs [ Time Frame: Up to 60 months ]
    To characterize the safety profile of TIL LN-144 (Lifileucel)/LN-145 in combination with pembrolizumab in MM, HNSCC, and NSCLC patients or TIL LN-145 as a single therapy in NSCLC patients and TIL LN-145-S1 in MM patients as measured by the incidence of Grade ≥ 3 treatment-emergent adverse events (TEAEs).
Original Primary Outcome Measures  ICMJE
 (submitted: August 22, 2018)
  • Objective Response Rate [ Time Frame: Up to 60 months ]
    To evaluate the efficacy of autologous TIL LN-144 (Lifileucel)/LN-145 as a single therapy or in combination with pembrolizumab in patients with metastatic melanoma, HNSCC, or NSCLC by determining the objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST 1.1).
  • Safety Profile Measured by Grade ≥3 TEAEs [ Time Frame: Up to 60 months ]
    To characterize the safety profile of TIL LN-144 (Lifileucel)/LN-145 as a single-therapy in NSCLC patients or in combination with pembrolizumab in metastatic melanoma and HNSCC patients as measured by the incidence of Grade ≥3 treatment-emergent adverse events (TEAEs).
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 22, 2018)
  • Complete Response Rate [ Time Frame: Up to 60 months ]
    To evaluate efficacy parameters such Complete Response (CR) rate per RECIST 1.1, as assessed by the Investigator
  • Duration of Response [ Time Frame: Up to 60 months ]
    To evaluate efficacy parameters such Duration of Response (DOR) per RECIST 1.1, as assessed by the Investigator
  • Disease Control Rate [ Time Frame: Up to 60 months ]
    To evaluate efficacy parameters such Disease Control Rate (DCR) per RECIST 1.1, as assessed by the Investigator
  • Progression-Free Survival [ Time Frame: Up to 60 months ]
    To evaluate efficacy parameters such Progression-Free Survival (PFS) per RECIST 1.1, as assessed by the Investigator
  • Overall Survival [ Time Frame: Up to 60 months ]
    To evaluate efficacy parameters such Overall Survival (OS)
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of Autologous Tumor Infiltrating Lymphocytes in Patients With Solid Tumors
Official Title  ICMJE A Phase 2, Multicenter Study of Autologous Tumor Infiltrating Lymphocytes (LN 144/LN-145/LN-145-S1) in Patients With Solid Tumors
Brief Summary 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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Metastatic Melanoma
  • Squamous Cell Carcinoma of the Head and Neck
  • Non-small Cell Lung Cancer
Intervention  ICMJE
  • Biological: Lifileucel
    A tumor sample is resected from each patient and cultured ex vivo to expand the population of tumor infiltrating lymphocytes. After NMA lymphodepletion, patients are infused with Lifileucel followed by IL-2 administration. Lifileucel will be administered to patients once (on Day 0) during the study.
    Other Name: LN-144, TIL, autologous tumor infiltrating lymphocytes, lifileucel
  • Biological: LN-145
    A tumor sample is resected from each patient and cultured ex vivo to expand the population of tumor infiltrating lymphocytes. After NMA lymphodepletion, patients are infused with their autologous TIL (LN-145) followed by IL-2 administration. TIL will be administered to patients once (on Day 0) during the study.
    Other Name: TIL, autologous tumor infiltrating lymphocytes
  • Drug: Pembrolizumab

    Humanized antibody.

    Pembrolizumab 200 mg IV or 400 mg IV will be administered following tumor resection and prior to NMA-LD. The next dose of pembrolizumab will be no earlier than following the completion of IL-2 and continue every 3 weeks at 200 mg IV or every 6 weeks at 400 mg IV thereafter for up to 2 years.

  • Biological: LN-145-S1
    A tumor sample is resected from each patient and cultured ex vivo to expand the population of tumor infiltrating lymphocytes. After NMA lymphodepletion, patients are infused with their autologous TIL (LN-145-S1) followed by IL-2 administration. TIL will be administered to patients once (on Day 0) during the study.
    Other Name: TIL, autologous tumor infiltrating lymphocytes
Study Arms  ICMJE
  • Experimental: Cohort 1A
    TIL 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.
    Interventions:
    • Biological: Lifileucel
    • Drug: Pembrolizumab
  • Experimental: Cohort 1B
    TIL 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 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.
    Intervention: Biological: LN-145-S1
  • Experimental: Cohort 2A
    TIL LN-145 therapy in combination with pembrolizumab in patients with advanced, recurrent, or metastatic HNSCC, with ≤ 3 prior lines of systemic therapy, excluding CPIs.
    Interventions:
    • Biological: LN-145
    • Drug: Pembrolizumab
  • Experimental: Cohort 3A
    TIL 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.
    Interventions:
    • Biological: LN-145
    • Drug: Pembrolizumab
  • Experimental: Cohort 3B
    TIL LN-145 therapy as a single agent in NSCLC, (Stage III-IV), who have previously received 1-3 lines of prior systemic therapy.
    Intervention: Biological: LN-145
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: February 26, 2020)
75
Original Estimated Enrollment  ICMJE
 (submitted: August 22, 2018)
36
Estimated Study Completion Date  ICMJE December 2024
Estimated Primary Completion Date December 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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: 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: MM patients must have previously received systemic therapy with a PD-1 blocking antibody. NSCLC patients must have previously received systemic therapy with any CPI (except for those patients with known oncogene drivers (eg, EGFR, ALK, ROS) who have mutations that are sensitive to targeted therapies) as part of 1 - 3 prior lines of 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 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
  • Cohort 1A, 2A and 3A patients may not have a medical history of autoimmune disorders requiring treatment or active management.
  • 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 not meeting the pulmonary function requirements as stated: 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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 12 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Iovance Biotherapeutics Study Team 866-565-4410 Clinical.Inquiries@iovance.com
Listed Location Countries  ICMJE Canada,   France,   Greece,   Spain,   Switzerland,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03645928
Other Study ID Numbers  ICMJE IOV-COM-202
2018-001608-12 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Iovance Biotherapeutics, Inc.
Study Sponsor  ICMJE Iovance Biotherapeutics, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Iovance Biotherapeutics Medical Monitor Iovance Biotherapeutics
PRS Account Iovance Biotherapeutics, Inc.
Verification Date September 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP