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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 : November 12, 2018
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. TIL as a single-therapy will be evaluated with LN-145 only.

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 Phase 2

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 1 and 2 will receive TIL plus pembrolizumab, and patients in Cohort 3 will receive TIL as a single therapy.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 36 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 or LN-145) in Patients With Solid Tumors
Estimated Study Start Date : November 2018
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 1
Lifileucel (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).
Biological: Lifileucel

A tumor sample is resected from each patient and cultured ex vivo to expand the population of tumor infiltrating lymphocytes. After lymphodepletion, patients are infused with Lifileucel followed by IL-2.

Lifileucel will be administered to patients once (on Day 0) during the study.

Other Name: LN-144

Drug: Pembrolizumab
Humanized antibody. Pembrolizumab 200 mg IV will be administered approximately every 3 weeks for up to 2 years.

Experimental: Cohort 2
TIL 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).
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.

Experimental: Cohort 3
TIL LN-145 therapy as a single-agent in NSCLC patients, who have previously received systemic therapy with checkpoint inhibitors (eg, anti-PD-1/anti-PD-L1).
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 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).

  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 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).


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

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

  • Patients must be ≥18 years and ≤70 years of age at the time of consent. Enrollment of patients >70 years of age may be allowed.
  • Must have a histologically confirmed unresectable or metastatic melanoma (Cohort 1), recurrent or metastatic squamous cell carcinoma of the head and neck (Cohort 2), or recurrent or metastatic non-small cell lung cancer (Cohort 3).
  • Cohort 1 and Cohort 2 only: must have not received prior immunotherapy, including checkpoint inhibitors (eg, anti-PD-1/anti-PD-L1 and/or anti-CTLA-4). With the excluded prior therapies cited, patients may have received from 1 to 3 prior systemic anticancer therapies.
  • Cohort 3 only: Patients with Stage III or Stage IV NSCLC (squamous, nonsquamous, adenocarcinoma, or large cell carcinoma) who have received from 1 to 3 prior systemic anticancer therapies, including checkpoint inhibitors (eg, anti-PD-1/anti-PD-L1) in the locally advanced or metastatic setting.
  • Must have remaining measurable disease as defined by RECIST 1.1 following tumor resection
  • Must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • Childbearing potential or their partners of childbearing potential must be willing to practice an approved method of birth control
  • Must have adequate organ function.
  • Must be seronegative for the human immunodeficiency virus (HIV).
  • Must have provided written authorization for use and disclosure of protected health information.

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.
  • Patients with symptomatic and/or untreated brain metastases
  • Patients who are on a systemic steroid therapy at a dose of >10mg of prednisone or equivalent a day. Short course of higher-dose steroid therapy is allowed.
  • 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 any form of primary immunodeficiency
  • Patients with a history of hypersensitivity to any component of the study drugs
  • Patients who have obstructive or restrictive pulmonary disease
  • 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 nonmyeloablative lymphodepletion (NMA-LD) 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
Contact: Iovance Biotherapeutics Study Team 866-565-4410 Clinical.Inquiries@iovance.com

Locations
United States, Connecticut
Yale University Recruiting
New Haven, Connecticut, United States, 06520
United States, Florida
Mount Sinai Medical Center Recruiting
Miami Beach, Florida, United States, 33140
United States, Kentucky
University of Louisville Recruiting
Louisville, Kentucky, United States, 40292
Sponsors and Collaborators
Iovance Biotherapeutics, Inc.
Investigators
Study Director: Iovance Biotherapeutics Medical Monitor Iovance Biotherapeutics

Responsible Party: Iovance Biotherapeutics, Inc.
ClinicalTrials.gov Identifier: NCT03645928     History of Changes
Other Study ID Numbers: IOV-COM-202
2018-001608-12 ( EudraCT Number )
First Posted: August 24, 2018    Key Record Dates
Last Update Posted: November 12, 2018
Last Verified: September 2018

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

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Carcinoma, Squamous Cell
Head and Neck Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms, Squamous Cell
Pembrolizumab
Antineoplastic Agents