Study Stopped
After reviewing the available safety and efficacy data to date, Iovance concluded that the study reached the required number of events for evaluation of study endpoints.
Study of Autologous Tumor Infiltrating Lymphocytes in Patients With Solid Tumors
A Phase 2, Multicenter Study of Autologous Tumor Infiltrating Lymphocytes (LN 144/LN-145/LN-145-S1) in Patients With Solid Tumors
3 other identifiers
interventional
225
7 countries
34
Brief Summary
A prospective, open-label, multi-cohort, non-randomized, multicenter Phase 2 study evaluating adoptive cell therapy (ACT) with TIL \[LN-144/LN-145 (lifileucel)\] in combination with immune checkpoint inhibitors or TIL \[LN-144/LN-145 (lifileucel) and LN-145-S1\] as a single agent therapy.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started May 2019
Longer than P75 for phase_2
34 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
August 22, 2018
CompletedFirst Posted
Study publicly available on registry
August 24, 2018
CompletedStudy Start
First participant enrolled
May 7, 2019
CompletedPrimary Completion
Last participant's last visit for primary outcome
February 20, 2026
CompletedStudy Completion
Last participant's last visit for all outcomes
February 20, 2026
CompletedMay 15, 2026
May 1, 2026
6.8 years
August 22, 2018
May 13, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (3)
Objective Response Rate
To evaluate the efficacy of autologous TIL in combination with ICIs in metastatic melanoma, HNSCC, and NSCLC patients and as a single therapy in metastatic melanoma and NSCLC patients as determined by objective response rate (ORR) using the Response Evaluation Criteria in Solid Tumors (RECIST 1.1) as assessed by Investigator
Up to 60 months
Safety Profile Measured by Grade ≥3 TEAEs
To characterize the safety profile of autologous TIL in combination with ICIs in metastatic melanoma, HNSCC, and NSCLC patients and as a single therapy in metastatic melanoma and NSCLC patients as measured by the incidence of Grade ≥ 3 treatment-emergent adverse events (TEAEs)
Up to 60 months
Percentage of patients for whom lifileucel is successfully manufactured and meets release specification
To evaluate the feasibility of producing lifileucel using tumor samples obtained before (Cohort 3D) or during (Cohort 3E) frontline platinum doublet chemotherapy and pembrolizumab in patients with Stage IV NSCLC
Up to 60 months
Secondary Outcomes (5)
Complete Response Rate
Up to 60 months
Duration of Response
Up to 60 months
Disease Control Rate
Up to 60 months
Progression-Free Survival
Up to 60 months
Overall Survival
Up to 60 months
Study Arms (10)
Cohort 1A
EXPERIMENTALLifileucel (LN-144) regimen in combination with pembrolizumab in patients with Stage IIIC to IV unresectable or metastatic melanoma with ≤ 3 prior lines of systemic therapy, excluding immune checkpoint inhibitors (ICI).
Cohort 1B
EXPERIMENTALLN-145-S1 regimen in patients with Stage IIIC or Stage IV unresectable or metastatic melanoma, who have previously received systemic therapy with a PD-1 blocking antibody. If the tumor is proto-oncogene B-Raf (BRAF) V600 mutation positive, patients must have received a BRAF inhibitor with or without a mitogen-activated extracellular signal-related kinase (MEK) inhibitor.
Cohort 1C
EXPERIMENTALLifileucel (LN-144 Generation 3 \[Gen 3\]) regimen in patients with Stage IIIC or Stage IV unresectable or metastatic melanoma, who have previously received systemic therapy with a PD-1 blocking antibody. If the tumor is BRAF V600 mutation positive, patients must have received BRAF inhibitor with or without a MEK inhibitor.
Cohort 2A
EXPERIMENTALLifileucel (LN-145) regimen in combination with pembrolizumab in patients with advanced, recurrent, or metastatic HNSCC, with ≤ 3 prior lines of systemic therapy, excluding ICIs.
Cohort 3A
EXPERIMENTALLifileucel (LN-145) regimen in combination with pembrolizumab in patients with locally advanced or metastatic (Stage III or Stage IV) non-small-cell lung cancer (NSCLC) with ≤ 3 prior lines of systemic therapy, excluding ICIs, or ≤ 4 lines if 2 or more of the lines are tyrosine kinase inhibitor (TKI) therapy for those with tumors that harbored actionable mutations (eg, EGFR, ALK, ROS).
Cohort 3B
EXPERIMENTALLifileucel (LN-145) regimen ent in patients with Stage III or Stage IV NSCLC, who have previously received 1-3 lines of prior systemic therapy. Patients with known oncogene drivers (eg, EGFR, ALK, ROS) who have mutations that are sensitive to targeted therapies are not required to have received prior systemic therapy with ICIs.
Cohort 3C
EXPERIMENTALLifileucel (LN-145) regimen in combination with ipilimumab and nivolumab in patients with Stage III or Stage IV NSCLC who have previously received 1 line of ICI monotherapy. No other systemic therapy for metastatic disease is allowed. Prior chemoradiation and/or chemotherapy in the adjuvant and/or neo-adjuvant settings are allowed.
Cohort 3D
EXPERIMENTALLifileucel regimen in combination with pembrolizumab with or without pemetrexed, given after tumor resection then 4 cycles of frontline platinum doublet chemotherapy plus pembrolizumab, in patients with Stage IV NSCLC without EGFR, ALK, or ROS1 driver mutations, who have had no prior therapy for advanced disease.
Cohort 3E
EXPERIMENTALLifileucel regimen in combination with pembrolizumab with or without pemetrexed, given after 4 cycles of frontline platinum doublet chemotherapy plus pembrolizumab with tumor resection between any 2 cycles, in patients with Stage IV NSCLC without EGFR, ALK, or ROS1 driver mutations.
Cohort 1D
EXPERIMENTALLifileucel (LN-144) regimen in combination with nivolumab-relatlimab in patients with Stage IIIC to IV unresectable or metastatic (advanced) melanoma who have had no prior therapy for advanced disease.
Interventions
A tumor sample is resected from each patient and cultured ex vivo to expand the population of tumor-infiltrating lymphocytes (TIL). After NMA-LD, patients receive lifileucel, followed by aldesleukin administration. Lifileucel will be administered to patients once (on Day 0) during the study.
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 aldesleukin administration. TIL will be administered to patients once (on Day 0) during the study.
Humanized antibody. Pembrolizumab will be administered after tumor resection and will continue every 3 weeks or every 6 weeks for up to 2 years.
A tumor sample is resected from each patient and cultured ex vivo to expand the population of TIL, then TIL with high levels of PD-1 surface expression are selected. After NMA-LD, patients receive their autologous PD-1-selected TIL (LN-145-S1), followed by aldesleukin administration. TIL will be administered to patients once (on Day 0) during the study.
Monoclonal antibody Ipilimumab will be administered as a single dose prior to tumor resection.
Monoclonal antibody. Nivolumab will be administered once prior to tumor resection. The second dose will be administered prior to starting NMA-LD and will continue every 4 weeks for up to 2 years.
Monoclonal antibody (nivolumab) and monoclonal antibody (relatlimab). Nivolumab-relatlimab will be administered after tumor resection and will continue every 4 weeks for up to 2 years.
Cisplatin administered intravenously at the protocol-defined dose every 3 weeks for up to 4 cycles.
Carboplatin administered intravenously at the protocol-defined dose every 3 weeks for up to 4 cycles.
Paclitaxel administered intravenously at the protocol-defined dose every 3 weeks for up to 4 cycles.
Pemetrexed administered intravenously at the protocol-defined dose every 3 weeks for up to 4 cycles. Optional continuation maintenance every 3 weeks, if applicable.
Nab-Paclitaxel administered intravenously at the protocol-defined dose every 3 weeks for up to 4 cycles.
Eligibility Criteria
You may qualify if:
- Must have a confirmed diagnosis of malignancy of their receptive \[RL7.1\]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). Stage IV NSCLC with no actionable mutations (EGFR, ALK, ROS1) with effective targeted therapy (Cohorts 3D and 3E).
- Cohorts 1A, 1D, 2A, 3A, 3D and 3E: If previously treated, patients must have progressed on or after most recent therapy and must not have received ICIs 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). Patients in Cohort 1D may have had no prior therapy for advanced disease. Patients in Cohorts 3D and 3E may have had no prior systemic therapy for Stage IV disease.
- 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 ICI (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 ICI 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, 1D, 2A, 3A, 3B, 3C, 3D and 3E. 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 aldesleukin, 4 months after their last dose of pembrolizumab, 5 months after their last dose of ipilimumab or nivolumab, or nivolumab-relatlimab; 6 months after the last dose of carboplatin; 14 months after the last dose of cisplatin; and 6 months after the last dose of pemetrexed, paclitaxel, or nab-paclitaxel, whichever occurs later.
You may not qualify if:
- 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 or history of leptomeningeal 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, 1D, 2A, 3A, 3C, 3D and 3E 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 to be administered in the pertinent cohort(s).
- Patients who have a left ventricular ejection fraction (LVEF) \< 45% or who are New York Heart Association Class II or higher. A cardiac stress test demonstrating any irreversible wall movement abnormality in any patients ≥60 years of age or in patients who have a history of ischemic heart disease, cardiac chest pain, or clinically significant atrial and/or ventricular arrhythmias.
- 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.
- Patients in Cohorts 1D, 3D, or 3E who previously received adjuvant or neoadjuvant ICI(s) for non-metastatic disease and had an immune-related AE(s) requiring systemic steroid treatment or discontinuation of immune checkpoint inhibitor therapy.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (34)
University of California, San Diego
La Jolla, California, 92093, United States
University of Southern California
Los Angeles, California, 90007, United States
University of California, Los Angeles
Los Angeles, California, 90095, United States
University of Colorado
Denver, Colorado, 80045, United States
Yale University
New Haven, Connecticut, 06520, United States
Georgetown University Medical Center
Washington D.C., District of Columbia, 20007, United States
Orlando Health Cancer Institute
Orlando, Florida, 32610, United States
Moffitt Cancer Center
Tampa, Florida, 33612, United States
University of Louisville
Louisville, Kentucky, 40292, United States
University of Maryland
Baltimore, Maryland, 21201, United States
Massachusetts General Hospital
Boston, Massachusetts, 02114, United States
Karmanos Cancer Institute
Detroit, Michigan, 48201, United States
Henry Ford Health System
Detroit, Michigan, 48202, United States
MD Anderson at Cooper
Camden, New Jersey, 08103, United States
Morristown Medical Center
Morristown, New Jersey, 07960, United States
Memorial Sloan Kettering Cancer Center
New York, New York, 10065, United States
University of Cincinnati
Cincinnati, Ohio, 45219, United States
Ohio State University
Columbus, Ohio, 43201, United States
Fred Hutchinson Cancer Research Center
Seattle, Washington, 98109, United States
Medical College of Wisconsin
Milwaukee, Wisconsin, 53226, United States
Princess Margaret Cancer Centre
Toronto, Ontario, M5G 2C1, Canada
Universitätsklinikum Schleswig-Holstein - Campus Lübeck
Lübeck, Schleswig-Holstein, 23538, Germany
Laiko General Hospital of Athens
Athens, Attica, 11527, Greece
Attikon University General Hospital
Athens, Attica, 12461, Greece
Hospital Universitario Marques de Valdecilla
Santander, Cantabria, 39008, Spain
Hospital Regional Universitario de Malaga - Hospital General
Málaga, Málaga, 29016, Spain
ICO l'Hospitalet - Hospital Duran i Reynals
Barcelona, 08908, Spain
Hospital Universitario Fundacion Jimenez Diaz
Madrid, 28040, Spain
Hospital Universitario 12 de Octubre
Madrid, 28041, Spain
Hospital Universitario HM Sanchinarro
Madrid, 28050, Spain
Universitaetsspital Bern
Bern, 3010, Switzerland
Centre Hospitalier Universitaire Vaudois
Lausanne, 1011, Switzerland
Guy's Hospital
London, England, SE19RT, United Kingdom
The Royal Marsden NHS Foundation Trust
London, England, SW3 6JJ, United Kingdom
Related Publications (1)
Hensel J, Metts J, Gupta A, Ladle BH, Pilon-Thomas S, Mullinax J. Adoptive Cellular Therapy for Pediatric Solid Tumors: Beyond Chimeric Antigen Receptor-T Cell Therapy. Cancer J. 2022 Jul-Aug 01;28(4):322-327. doi: 10.1097/PPO.0000000000000603.
PMID: 35880942DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Iovance Biotherapeutics Medical Monitor
Iovance Biotherapeutics
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
August 22, 2018
First Posted
August 24, 2018
Study Start
May 7, 2019
Primary Completion
February 20, 2026
Study Completion
February 20, 2026
Last Updated
May 15, 2026
Record last verified: 2026-05