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

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ClinicalTrials.gov Identifier: NCT04614103
Recruitment Status : Recruiting
First Posted : November 3, 2020
Last Update Posted : August 2, 2021
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 NSCLC.

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, autologous 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 an NMA lymphocyte depleting 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 (LN-145) in Patients With Metastatic Non-Small-Cell Lung Cancer
Actual Study Start Date : May 7, 2021
Estimated Primary Completion Date : December 2022
Estimated Study Completion Date : December 2026

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Cohort 1
Patients whose tumors did not express programmed cell death-ligand 1 (PD-L1) (tumor proportion score [TPS] < 1%) prior to their CPI 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 NMA lymphodepletion, patients are infused with their autologous TIL (LN-145) followed by IL-2 administration.
Other Name: TIL, Autologous Tumor Infiltrating Lymphocytes

Experimental: Cohort 2
Patients whose tumors expressed PD-L1 (TPS ≥ 1%) prior to their CPI 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 NMA lymphodepletion, patients are infused with their autologous TIL (LN-145) followed by IL-2 administration.
Other Name: TIL, Autologous Tumor Infiltrating Lymphocytes

Experimental: Cohort 3

Patients whose tumors do not express PD-L1 (TPS < 1%) prior to their CPI treatment and who are unable to safely undergo a surgical harvest for TIL generation due to at least one of the following:

  • Unacceptable surgical risk
  • Surgically approachable lesion is required for Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 assessment
Biological: LN-145
A tumor sample is harvested via core biopsy 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.
Other Name: TIL, Autologous Tumor Infiltrating Lymphocytes

Experimental: Cohort 4
Patients who have been previously treated with LN-145 in Cohort 1, 2, or 3 of this study.
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.
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 in patients with metastatic NSCLC without an actionable driver mutation who have disease progression on or following a single line of approved systemic therapy consisting of combined immune checkpoint inhibitor(s) (CPI[s]) + chemotherapy ± bevacizumab, as determined by objective response rate (ORR), using the RECIST v1.1, as assessed by the Independent Review Committee (IRC) (Cohorts 1 and 2) or by the Investigator (Cohorts 3 and 4)


Secondary Outcome Measures :
  1. Objective Response Rate [ Time Frame: Up to 60 months ]
    To evaluate efficacy parameters such as Objective Response Rate (ORR) per RECIST v1.1

  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 NSCLC patients, as measured by the incidence of Grade ≥ 3 treatment-emergent adverse events (TEAEs)

  8. Core Biopsies [ Time Frame: Up to 60 months ]
    For Cohort 3 only: To evaluate the efficiency of generating LN-145 from tumor core biopsies; Percentage successful TIL products generated from core biopsies



Information from the National Library of Medicine

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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:

  • Confirmed histologic diagnosis of Non-Small-Cell Lung Carcinoma confirmation.
  • Have received a single line of systemic therapy that included CPI and chemotherapy with documented radiographic disease progression on or following this single line of systemic therapy.
  • LVEF > 45%, NYHA Class 1; cardiac stress test required
  • FEV1>50% or FEV1/FVC>0.7 (6 min walk test if unable to perform or unreliable spirometry).
  • At least 1 resectable lesion.
  • Previously irradiated lesion must have radiographic progression prior to harvest.
  • 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 highly effective birth control during treatment and for 12 months after receiving all protocol-related therapy.

Exclusion Criteria:

  • Patients who have known oncogene driver mutations (eg, EGFR, ALK, ROS) which are sensitive to targeted therapies.
  • Patients who have symptomatic and/or untreated brain metastases.
  • Patients who have organ allograft or prior cell transfer within the past 20 years.
  • 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 have any form of primary immunodeficiency
  • 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 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): NCT04614103


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

Locations
Show Show 17 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 2, 2021
Last Verified: July 2021

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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
Lung Carcinoma
LN145
PD-L1
Stage IV Cancer
Stage IV Lung Cancer
Stage IV Non-Small Cell Lung Cancer
Stage IV NSCLC
Systemic Therapy
2nd line therapy
Second line therapy
CPI
Check point inhibitor
Metastatic NSCLC
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