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Trial record 1 of 1 for:    IOV-COM-202
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Study of Autologous Tumor Infiltrating Lymphocytes in Patients With Solid Tumors

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ClinicalTrials.gov Identifier: NCT03645928
Recruitment Status : Recruiting
First Posted : August 24, 2018
Last Update Posted : February 28, 2020
Sponsor:
Information provided by (Responsible Party):
Iovance Biotherapeutics, Inc.

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.

Condition or disease Intervention/treatment Phase
Metastatic Melanoma Squamous Cell Carcinoma of the Head and Neck Non-small Cell Lung Cancer Biological: Lifileucel Biological: LN-145 Drug: Pembrolizumab Biological: LN-145-S1 Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 75 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2, Multicenter Study of Autologous Tumor Infiltrating Lymphocytes (LN 144/LN-145/LN-145-S1) in Patients With Solid Tumors
Actual Study Start Date : May 7, 2019
Estimated Primary Completion Date : December 2023
Estimated Study Completion Date : December 2024

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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.
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

Drug: Pembrolizumab
Humanized antibody. Pembrolizumab 200 mg IV will be administered approximately every 3 weeks for up to 2 years or until disease progression or unacceptable toxicity.

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 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.
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

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.
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 will be administered approximately every 3 weeks for up to 2 years or until disease progression or unacceptable toxicity.

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.
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 will be administered approximately every 3 weeks for up to 2 years or until disease progression or unacceptable toxicity.

Experimental: Cohort 3B
TIL 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.
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




Primary Outcome Measures :
  1. 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 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.

  2. 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).


Secondary Outcome Measures :
  1. 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

  2. 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

  3. 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

  4. 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

  5. Overall Survival [ Time Frame: Up to 60 months ]
    To evaluate efficacy parameters such Overall Survival (OS)



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   12 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03645928


Contacts
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Contact: Iovance Biotherapeutics Study Team 866-565-4410 Clinical.Inquiries@iovance.com

Locations
Show Show 29 study locations
Sponsors and Collaborators
Iovance Biotherapeutics, Inc.
Investigators
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Study Director: Iovance Biotherapeutics Medical Monitor Iovance Biotherapeutics
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Responsible Party: Iovance Biotherapeutics, Inc.
ClinicalTrials.gov Identifier: NCT03645928    
Other Study ID Numbers: IOV-COM-202
2018-001608-12 ( EudraCT Number )
First Posted: August 24, 2018    Key Record Dates
Last Update Posted: February 28, 2020
Last Verified: February 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Iovance Biotherapeutics, Inc.:
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
Additional relevant MeSH terms:
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Squamous Cell Carcinoma of Head and Neck
Neoplasms by Site
Neoplasms
Neoplasms by Histologic Type
Carcinoma, Squamous Cell
Carcinoma
Neoplasms, Glandular and Epithelial
Head and Neck Neoplasms
Pembrolizumab
Antineoplastic Agents, Immunological
Antineoplastic Agents