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Autologous LN-145 in Patients With Metastatic Non-Small-Cell Lung Cancer

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: NCT04614103
Recruitment Status : Recruiting
First Posted : November 3, 2020
Last Update Posted : August 9, 2022
Sponsor:
Information provided by (Responsible Party):
Iovance Biotherapeutics, Inc.

Brief Summary:
This is a prospective, open-label, multi-cohort, non-randomized, multicenter phase 2 study evaluating LN-145 in patients with metastatic non-small-cell lung cancer

Condition or disease Intervention/treatment Phase
Metastatic Non Small Cell Lung Cancer Biological: LN-145 Phase 2

Detailed Description:
LN-145 is a ready-to-infuse TIL therapy that utilizes an autologous TIL manufacturing process, as originally developed by the NCI and further optimized by Iovance for the treatment of patients with metastatic NSCLC. The cell transfer therapy used in this study involves patients receiving a non-myeloablative (NMA) lymphodepleting preparative regimen, followed by infusion of autologous TIL, then finally followed by the administration of IL-2.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 95 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 (TIL or LN-145) in Patients With Metastatic Non-Small-Cell Lung Cancer
Actual Study Start Date : May 7, 2021
Estimated Primary Completion Date : June 2024
Estimated Study Completion Date : December 2026

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer

Arm Intervention/treatment
Experimental: Cohort 1
Patients whose tumors did not express programmed cell death-ligand 1 (PD-L1), i.e., tumor proportion score (TPS) < 1% prior to ICI treatment and Patients with no available historical TPS for PD-L1 expression
Biological: LN-145
A tumor sample is resected from each patient and cultured ex vivo to expand the population of tumor infiltrating lymphocytes. After lymphodepleting chemotherapy including cyclophosphamide and fludarabine, patient is infused with autologous TIL (LN-145), followed by IL-2.
Other Name: TIL, Autologous Tumor Infiltrating Lymphocytes

Experimental: Cohort 2
Patients whose tumors expressed PD-L1 TPS ≥1% prior to ICI treatment
Biological: LN-145
A tumor sample is resected from each patient and cultured ex vivo to expand the population of tumor infiltrating lymphocytes. After lymphodepleting chemotherapy including cyclophosphamide and fludarabine, patient is infused with autologous TIL (LN-145), followed by IL-2.
Other Name: TIL, Autologous Tumor Infiltrating Lymphocytes

Experimental: Cohort 3
Patients, regardless of tumor PD-L1 TPS prior to ICI treatment, who are unable to safely undergo a surgical tumor resection for TIL generation
Biological: LN-145
A tumor sample is obtained by image-guided core biopsy from each patient and cultured ex vivo to expand the population of tumor infiltrating lymphocytes. After lymphodepleting chemotherapy including cyclophosphamide and fludarabine, patient is infused with autologous TIL (LN-145) followed by IL-2.
Other Name: TIL, Autologous Tumor Infiltrating Lymphocytes

Experimental: Retreatment Cohort
Patients who were previously treated with LN-145 in Cohort 1, 2, or 3.
Biological: LN-145
A tumor sample is resected from each patient and cultured ex vivo to expand the population of tumor infiltrating lymphocytes. After lymphodepleting chemotherapy including cyclophosphamide and fludarabine, patient is infused with autologous TIL (LN-145), followed by IL-2.
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 LN-145 as determined by objective response rate (ORR) in patients with metastatic NSCLC using the Response Evaluation Criteria in Solid Tumors (RECIST v1.1), as assessed by central review for Cohorts 1 and 2 and by the investigator for Cohort 3 and the Retreatment Cohort


Secondary Outcome Measures :
  1. Objective Response Rate [ Time Frame: Up to 60 months ]
    To evaluate the efficacy of LN-145 as determined by objective response rate (ORR) per RECIST v1.1, as assessed by the Investigator for Cohorts 1 and 2

  2. Complete Response Rate [ Time Frame: Up to 60 months ]
    To evaluate efficacy parameters such as Complete Response Rate (CRR) per RECIST v1.1

  3. Duration of Response [ Time Frame: Up to 60 months ]
    To evaluate efficacy parameters such as Duration of Response (DOR) rate per RECIST v1.1

  4. Disease Control Rate [ Time Frame: Up to 60 months ]
    To evaluate efficacy parameters such as Disease Control Rate (DCR) per RECIST v1.1

  5. Progression-Free Survival [ Time Frame: Up to 60 months ]
    To evaluate efficacy parameters such as Progression-Free Survival (PFS) per RECIST v1.1

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

  7. Adverse Events [ Time Frame: Up to 60 months ]
    To characterize the safety profile of LN-145 in patients with non-small-cell lung cancer (NSCLC)

  8. Core Biopsies [ Time Frame: Up to 60 months ]
    To determine the feasibility of generating LN-145 using tumor tissue obtained via image-guided core biopsy



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:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Have historically or pathologically confirmed diagnosis of metastatic Stage IV NSCLC without EGFR, ALK, or ROS genomic alterations.
  • For patients who have actionable mutations (other than EGFR, ALK, or ROS genomic alterations), 1 additional line of therapy with the appropriate targeted therapy will be allowed.
  • Patients must have documented radiographic disease progression on or after the first-line therapy, including concurrent or sequential ICI and platinum-based chemotherapy ± bevacizumab. No more than 1 prior line is allowed if ICI and platinum-based chemotherapy were administered concurrently and no more than 2 prior lines are allowed for sequential administration of platinum-based chemotherapy and ICI as 2 separate lines.
  • LN-145 manufacture is allowed for patients who have residual resectable disease after completion of the platinum-based chemotherapy component of the front-line ICI and platinum-based chemotherapy combination and meet all eligibility criteria except documented disease progression. These patients must intend to receive TIL therapy after disease progression
  • Prior systemic therapy in the adjuvant or neoadjuvant setting, or as part of definitive chemoradiotherapy, will count as a line of therapy if the patient had disease progression during or within 12 months after the completion of such therapy.
  • At least 1 resectable lesion for TIL production and at least one remaining measurable lesion, as defined by RECIST v1.1
  • Have adequate organ function
  • LVEF > 45%, NYHA Class 1
  • Have adequate pulmonary function
  • ECOG performance status of 0 or 1
  • Patients of childbearing potential or those with partners of childbearing potential must be willing to practice an approved method of highly effective birth control during treatment and up to 12 months after all protocol-related therapy

Exclusion Criteria:

  • Patients who have EGFR, ALK or ROS driver mutations
  • Patients who have symptomatic, untreated brain metastases.
  • Patients who have had allogeneic organ transplant or prior cell therapy within the past 20 years
  • Patients who have any form of primary immunodeficiency
  • Patients who are on systemic steroid therapy ≥ 10 mg/day of prednisone or equivalent.
  • Patients who have received a live or attenuated vaccination within 28 days prior to the start of treatment
  • Patients who have had another primary malignancy within the previous 3 years
  • Participation in another interventional clinical study within 21 days

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): NCT04614103


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

Locations
Show Show 38 study locations
Sponsors and Collaborators
Iovance Biotherapeutics, Inc.
Investigators
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Study Director: Iovance Biotherapeutics Study Team Iovance Biotherapeutics
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Responsible Party: Iovance Biotherapeutics, Inc.
ClinicalTrials.gov Identifier: NCT04614103    
Other Study ID Numbers: IOV-LUN-202
2020-003629-45 ( EudraCT Number )
First Posted: November 3, 2020    Key Record Dates
Last Update Posted: August 9, 2022
Last Verified: August 2022

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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-145
Cell Therapy
Autologous Adoptive Cell Therapy
Cellular Immuno-therapy
Tumor Infiltrating Lymphocytes
TIL
IL-2
Non Small Cell Lung Cancer
NSCLC
Second line Lung Cancer
Bronchial Neoplasms
Carcinoma
Lung Disease
Metastatic Lung Cancer
Metastatic Non Small Cell Lung Cancer
Metastatic NSCLC
Lung Carcinoma
PD-L1
Stage IV Lung Cancer
Stage IV Non-Small Cell Lung Cancer
Stage IV NSCLC
Systemic Therapy
2nd line therapy
Second line therapy
CPI
Immune checkpoint inhibitor (ICI)
NSCLC Recurrent
Recurrent Lung Cancer
Recurrent Lung Carcinoma
Additional relevant MeSH terms:
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Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms