Trial Title:
Study of Autologous Tumor Infiltrating Lymphocytes in Patients With Solid Tumors
NCT ID:
NCT03645928
Condition:
Metastatic Melanoma
Squamous Cell Carcinoma of the Head and Neck
Non-small Cell Lung Cancer
Conditions: Official terms:
Squamous Cell Carcinoma of Head and Neck
Pembrolizumab
Nivolumab
Ipilimumab
Conditions: Keywords:
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
Ipilimumab
Nivolumab
CPI
Checkpoint Inhibitor
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Biological
Intervention name:
Lifileucel
Description:
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.
Arm group label:
Cohort 1A
Arm group label:
Cohort 1C
Other name:
LN-144, TIL, autologous tumor infiltrating lymphocytes, lifileucel
Intervention type:
Biological
Intervention name:
LN-145
Description:
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.
Arm group label:
Cohort 2A
Arm group label:
Cohort 3A
Arm group label:
Cohort 3B
Arm group label:
Cohort 3C
Other name:
TIL, autologous tumor infiltrating lymphocytes
Intervention type:
Drug
Intervention name:
Pembrolizumab
Description:
Humanized antibody.
Pembrolizumab will be administered following tumor resection and will continue every 3
weeks or every 6 weeks thereafter for up to 2 years.
Arm group label:
Cohort 1A
Arm group label:
Cohort 2A
Arm group label:
Cohort 3A
Other name:
Keytruda
Intervention type:
Biological
Intervention name:
LN-145-S1
Description:
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.
Arm group label:
Cohort 1B
Other name:
TIL, autologous tumor infiltrating lymphocytes
Intervention type:
Drug
Intervention name:
Ipilimumab
Description:
Monoclonal antibody
Ipilimumab will be administered as a single dose prior to tumor resection.
Arm group label:
Cohort 3C
Other name:
Yervoy
Intervention type:
Drug
Intervention name:
Nivolumab
Description:
Monoclonal antibody
Nivolumab will be administered once prior to tumor resection. The second dose will be
administered prior to TIL administration and dosing will continue every 4 weeks for up to
2 years.
Arm group label:
Cohort 3C
Other name:
Opdivo
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 checkpoint inhibitors or TIL LN-144 (Lifileucel)/LN-145/LN-145-S1 as a single agent
therapy.
Detailed description:
LN-144 (Lifileucel)/LN-145/LN-145-S1 is an adoptive cell transfer therapy that utilizes
an autologous TIL for the treatment of patients with unresectable or metastatic melanoma,
advanced, recurrent, or metastatic squamous cell carcinoma of the head and neck, and
locally advanced or metastatic 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, 2A, 3A and 3C will receive
TIL plus checkpoint inhibitors. Patients in Cohorts 1B, 1C, and 3B will receive
autologous TIL as a single therapy.
Criteria for eligibility:
Criteria:
Inclusion Criteria
- Must have a confirmed diagnosis of malignancy of their receptive histologies:
unresectable or metastatic melanoma Stage IIIC to IV (Cohorts 1A,1B and 1C),
advanced, recurrent or metastatic HNSCC (Cohort 2A), or Stage III or Stage IV
non-small cell lung cancer (Cohorts 3A, 3B, and 3C).
- 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. Patients may have received up to 3 prior systemic anticancer therapies
(except for Cohort 3A, where patients whose tumors harbor actionable mutations may
have received up to 4 prior systemic therapies)
- Cohorts 1B, 1C, 3B, and 3C: Unresectable or metastatic melanoma patients in Cohorts
1B or 1C must have previously received systemic therapy with a PD-1 blocking
antibody. NSCLC patients in Cohort 3B must have previously received systemic therapy
with any CPI (except for those patients with known oncogene driver mutations that
are sensitive to targeted therapies) as part of 1 - 3 prior lines of therapy. NSCLC
patients in Cohort 3C must have previously received 1 line of CPI monotherapy. No
other systemic therapy for metastatic disease is allowed. Prior chemoradiation
and/or chemotherapy in the adjuvant and/or neoadjuvant settings are allowed.
- Must have at least 1 resectable lesion
- Must have remaining measurable disease as defined by RECIST 1.1 following tumor
resection
- Must be ≥ 18 years at the time of consent for Cohorts 1A, 1C, 2A, 3A, 3B, and 3C.
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 their last dose of IL-2, 4 months after their last dose of
pembrolizumab, or 5 months after their last dose of ipilimumab or nivolumab,
whichever occurs later.
Exclusion Criteria
- Patients with melanoma of uveal/ocular origin.
- Patients who have a history of allogeneic organ transplant or any form of cell
therapy involving prior conditioning chemotherapy within the past 20 years. Patients
being retreated with TIL, as part of this study are not excluded.
- Patients who have symptomatic, 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, 3A, and 3C patients may not have a medical history of autoimmune
disorders (including pneumonitis) 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 with respiratory dysfunction or history of smoking are excluded if not
meeting either of forced expiratory volume in 1 second (FEV1)/forced vital capacity
(FVC) > 0.7 or FEV1 > 50%.
- Patients who have had another primary malignancy within the previous 3 years
- Participation in another interventional clinical study within 21 days prior to the
initiation of treatment.
Gender:
All
Minimum age:
12 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
University of California, San Diego
Address:
City:
La Jolla
Zip:
92093
Country:
United States
Status:
Terminated
Facility:
Name:
University of Southern California
Address:
City:
Los Angeles
Zip:
90007
Country:
United States
Status:
Active, not recruiting
Facility:
Name:
University of California, Los Angeles
Address:
City:
Los Angeles
Zip:
90095
Country:
United States
Status:
Active, not recruiting
Facility:
Name:
University of Colorado
Address:
City:
Denver
Zip:
80045
Country:
United States
Status:
Active, not recruiting
Facility:
Name:
Yale University
Address:
City:
New Haven
Zip:
06520
Country:
United States
Status:
Active, not recruiting
Facility:
Name:
Georgetown University Medical Center
Address:
City:
Washington
Zip:
20007
Country:
United States
Status:
Active, not recruiting
Facility:
Name:
Mount Sinai Medical Center
Address:
City:
Miami Beach
Zip:
33140
Country:
United States
Status:
Withdrawn
Facility:
Name:
Orlando Health Cancer Institute
Address:
City:
Orlando
Zip:
32610
Country:
United States
Status:
Recruiting
Facility:
Name:
Moffitt Cancer Center
Address:
City:
Tampa
Zip:
33612
Country:
United States
Status:
Active, not recruiting
Facility:
Name:
University of Louisville
Address:
City:
Louisville
Zip:
40292
Country:
United States
Status:
Recruiting
Facility:
Name:
University of Maryland
Address:
City:
Baltimore
Zip:
21201
Country:
United States
Status:
Active, not recruiting
Facility:
Name:
Massachusetts General Hospital
Address:
City:
Boston
Zip:
02114
Country:
United States
Status:
Recruiting
Facility:
Name:
Karmanos Cancer Institute
Address:
City:
Detroit
Zip:
48201
Country:
United States
Status:
Active, not recruiting
Facility:
Name:
Henry Ford Health System
Address:
City:
Detroit
Zip:
48202
Country:
United States
Status:
Active, not recruiting
Facility:
Name:
MD Anderson at Cooper
Address:
City:
Camden
Zip:
08103
Country:
United States
Status:
Recruiting
Facility:
Name:
Morristown Medical Center
Address:
City:
Morristown
Zip:
07960
Country:
United States
Status:
Recruiting
Facility:
Name:
Columbia University
Address:
City:
New York
Zip:
10027
Country:
United States
Status:
Withdrawn
Facility:
Name:
Memorial Sloan Kettering Cancer Center
Address:
City:
New York
Zip:
10065
Country:
United States
Status:
Active, not recruiting
Facility:
Name:
University of Cincinnati
Address:
City:
Cincinnati
Zip:
45219
Country:
United States
Status:
Terminated
Facility:
Name:
Ohio State University
Address:
City:
Columbus
Zip:
43201
Country:
United States
Status:
Recruiting
Facility:
Name:
Avera Cancer Institute
Address:
City:
Sioux Falls
Zip:
57105
Country:
United States
Status:
Withdrawn
Facility:
Name:
Huntsman Cancer Hospital
Address:
City:
Salt Lake City
Zip:
84112
Country:
United States
Status:
Withdrawn
Facility:
Name:
Fred Hutchinson Cancer Research Center
Address:
City:
Seattle
Zip:
98109
Country:
United States
Status:
Recruiting
Facility:
Name:
Medical College of Wisconsin
Address:
City:
Milwaukee
Zip:
53226
Country:
United States
Status:
Terminated
Facility:
Name:
Princess Margaret Cancer Centre
Address:
City:
Toronto
Zip:
M5G 2C1
Country:
Canada
Status:
Active, not recruiting
Facility:
Name:
Centre Léon Berard
Address:
City:
Lyon
Zip:
69008
Country:
France
Status:
Withdrawn
Facility:
Name:
Klinikum rechts der Isar der Technischen Universität München
Address:
City:
München
Zip:
81675
Country:
Germany
Status:
Recruiting
Facility:
Name:
Universitätsklinikum Carl Gustav Carus
Address:
City:
Dresden
Zip:
01307
Country:
Germany
Status:
Withdrawn
Facility:
Name:
Universitätsklinikum Schleswig-Holstein - Campus Lübeck
Address:
City:
Lübeck
Zip:
23538
Country:
Germany
Status:
Recruiting
Facility:
Name:
Laiko General Hospital of Athens
Address:
City:
Athens
Zip:
11527
Country:
Greece
Status:
Recruiting
Facility:
Name:
Attikon University General Hospital
Address:
City:
Athens
Zip:
12461
Country:
Greece
Status:
Active, not recruiting
Facility:
Name:
Hospital Universitario Marques de Valdecilla
Address:
City:
Santander
Zip:
39008
Country:
Spain
Status:
Recruiting
Facility:
Name:
University Hospital Vall d'Hebron
Address:
City:
Barcelona
Zip:
08035
Country:
Spain
Status:
Withdrawn
Facility:
Name:
ICO l'Hospitalet - Hospital Duran i Reynals
Address:
City:
Barcelona
Zip:
08908
Country:
Spain
Status:
Recruiting
Facility:
Name:
Hospital General Universitario Gregorio Marañón
Address:
City:
Madrid
Zip:
28007
Country:
Spain
Status:
Withdrawn
Facility:
Name:
Hospital Universitario Fundacion Jimenez Diaz
Address:
City:
Madrid
Zip:
28040
Country:
Spain
Status:
Recruiting
Facility:
Name:
Hospital Universitario 12 de Octubre
Address:
City:
Madrid
Zip:
28041
Country:
Spain
Status:
Recruiting
Facility:
Name:
Hospital Universitario HM Sanchinarro
Address:
City:
Madrid
Zip:
28050
Country:
Spain
Status:
Recruiting
Facility:
Name:
Hospital Regional Universitario de Malaga - Hospital General
Address:
City:
Málaga
Zip:
29016
Country:
Spain
Status:
Terminated
Facility:
Name:
Universitätsspital Basel
Address:
City:
Basel
Zip:
4031
Country:
Switzerland
Status:
Withdrawn
Facility:
Name:
Universitaetsspital Bern
Address:
City:
Bern
Zip:
3010
Country:
Switzerland
Status:
Active, not recruiting
Facility:
Name:
Centre Hospitalier Universitaire Vaudois
Address:
City:
Lausanne
Zip:
1011
Country:
Switzerland
Status:
Terminated
Facility:
Name:
Guy's Hospital
Address:
City:
London
Zip:
SE19RT
Country:
United Kingdom
Status:
Recruiting
Facility:
Name:
The Royal Marsden NHS Foundation Trust
Address:
City:
London
Zip:
SW3 6JJ
Country:
United Kingdom
Status:
Recruiting
Facility:
Name:
Bristol Haematology and Oncology Centre
Address:
City:
Bristol
Zip:
BS2 8ED
Country:
United Kingdom
Status:
Withdrawn
Start date:
May 7, 2019
Completion date:
August 9, 2029
Lead sponsor:
Agency:
Iovance Biotherapeutics, Inc.
Agency class:
Industry
Source:
Iovance Biotherapeutics, Inc.
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT03645928
