Metastatic MelanomaPhase 2NCT03645928
Study of Autologous Tumor Infiltrating Lymphocytes in Patients With Solid Tumors
A Phase 2 study testing Lifileucel, LN-145 and Pembrolizumab in people with Metastatic Melanoma and Squamous Cell Carcinoma of the Head and Neck, run by Iovance Biotherapeutics, Inc. at 34 sites in 7 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Melanoma, Squamous Cell Carcinoma of the Head and Neck, Non-small Cell Lung Cancer
- What is being tested?
- Lifileucel, LN-145 and Pembrolizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 225 participants
- Where
- 34 sitesin 7 countries
- Study dates
- 7 May 2019to 20 Feb 2026
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 15Show fewer
- 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.
Trial locations and contacts
34 sites in 7 countries.
34 sites in 7 countries
United States20 sites
University of Maryland
Baltimore, Maryland, 21201
Massachusetts General Hospital
Boston, Massachusetts, 02114
MD Anderson at Cooper
Camden, New Jersey, 08103
University of Cincinnati
Cincinnati, Ohio, 45219
Ohio State University
Columbus, Ohio, 43201
University of Colorado
Denver, Colorado, 80045
Karmanos Cancer Institute
Detroit, Michigan, 48201
Henry Ford Health System
Detroit, Michigan, 48202
University of California, San Diego
La Jolla, California, 92093
University of Southern California
Los Angeles, California, 90007
University of California, Los Angeles
Los Angeles, California, 90095
University of Louisville
Louisville, Kentucky, 40292
Medical College of Wisconsin
Milwaukee, Wisconsin, 53226
Morristown Medical Center
Morristown, New Jersey, 07960
Yale University
New Haven, Connecticut, 06520
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
Orlando Health Cancer Institute
Orlando, Florida, 32610
Fred Hutchinson Cancer Research Center
Seattle, Washington, 98109
Moffitt Cancer Center
Tampa, Florida, 33612
Georgetown University Medical Center
Washington D.C., District of Columbia, 20007
Spain6 sites
ICO l'Hospitalet - Hospital Duran i Reynals
Barcelona, 08908
Hospital Universitario Fundacion Jimenez Diaz
Madrid, 28040
Hospital Universitario 12 de Octubre
Madrid, 28041
Hospital Universitario HM Sanchinarro
Madrid, 28050
Hospital Regional Universitario de Malaga - Hospital General
Málaga, Málaga, 29016
Hospital Universitario Marques de Valdecilla
Santander, Cantabria, 39008
Greece2 sites
Laiko General Hospital of Athens
Athens, Attica, 11527
Attikon University General Hospital
Athens, Attica, 12461
Switzerland2 sites
Universitaetsspital Bern
Bern, 3010
Centre Hospitalier Universitaire Vaudois
Lausanne, 1011
United Kingdom2 sites
Guy's Hospital
London, England, SE19RT
The Royal Marsden NHS Foundation Trust
London, England, SW3 6JJ
Germany1 site
Universitätsklinikum Schleswig-Holstein - Campus Lübeck
Lübeck, Schleswig-Holstein, 23538
About this study
Official title: A Phase 2, Multicenter Study of Autologous Tumor Infiltrating Lymphocytes (LN 144/LN-145/LN-145-S1) in Patients With Solid Tumors
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.
Read the detailed description
TIL [LN-144/LN-145 (lifileucel) and 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 lymphodepletion (NMA-LD) regimen, followed by autologous TIL infusion , then aldesleukin administration. Patients in Cohorts 1A, 1D, 2A, 3A, 3C, 3D, and 3E will receive TIL plus immune checkpoint inhibitors. Patients in Cohorts 1B, 1C, and 3B will receive autologous TIL as a single therapy.
- Conditions
- Metastatic Melanoma, Squamous Cell Carcinoma of the Head and Neck, Non-small Cell Lung Cancer
- Being tested
- Lifileucel, LN-145, Pembrolizumab, LN-145-S1, Ipilimumab
- 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, ICI, Immune Checkpoint Inhibitor, Aldesleukin, Non-small cell lung cancer, Melanoma
- Medical subject headings
- Melanoma, Squamous Cell Carcinoma of Head and Neck, Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LifileucelBiological
Also called LN-144, TIL, autologous tumor-infiltrating lymphocytes
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.
LN-145Biological
Also called TIL, autologous tumor infiltrating lymphocytes
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.
PembrolizumabDrug
Also called Keytruda
Humanized antibody. Pembrolizumab will be administered after tumor resection and will continue every 3 weeks or every 6 weeks for up to 2 years.
LN-145-S1Biological
Also called TIL, autologous tumor-infiltrating lymphocytes, PD-1-selected TIL
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.
IpilimumabDrug
Also called Yervoy
Monoclonal antibody
Ipilimumab will be administered as a single dose prior to tumor resection.
NivolumabDrug
Also called Opdivo
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.
Nivolumab-relatlimabDrug
Also called Opdualag
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.
CisplatinDrug
Cisplatin administered intravenously at the protocol-defined dose every 3 weeks for up to 4 cycles.
CarboplatinDrug
Carboplatin administered intravenously at the protocol-defined dose every 3 weeks for up to 4 cycles.
PaclitaxelDrug
Paclitaxel administered intravenously at the protocol-defined dose every 3 weeks for up to 4 cycles.
Nab paclitaxelDrug
Nab-Paclitaxel administered intravenously at the protocol-defined dose every 3 weeks for up to 4 cycles.
PemetrexedDrug
Pemetrexed administered intravenously at the protocol-defined dose every 3 weeks for up to 4 cycles. Optional continuation maintenance every 3 weeks, if applicable.
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1A | Experimental | Lifileucel (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). Receives: Biological: Lifileucel; Drug: Pembrolizumab |
| Cohort 1B | Experimental | LN-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. Receives: Biological: LN-145-S1 |
| Cohort 1C | Experimental | Lifileucel (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. Receives: Biological: Lifileucel |
| Cohort 2A | Experimental | Lifileucel (LN-145) regimen in combination with pembrolizumab in patients with advanced, recurrent, or metastatic HNSCC, with ≤ 3 prior lines of systemic therapy, excluding ICIs. Receives: Biological: Lifileucel; Biological: LN-145; Drug: Pembrolizumab |
| Cohort 3A | Experimental | Lifileucel (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). Receives: Biological: Lifileucel; Biological: LN-145; Drug: Pembrolizumab |
| Cohort 3B | Experimental | Lifileucel (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. Receives: Biological: Lifileucel; Biological: LN-145 |
| Cohort 3C | Experimental | Lifileucel (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. Receives: Biological: Lifileucel; Biological: LN-145; Drug: Ipilimumab; Drug: Nivolumab |
| Cohort 3D | Experimental | Lifileucel 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. Receives: Biological: Lifileucel; Biological: LN-145; Drug: Pembrolizumab; Drug: Cisplatin; Drug: Carboplatin; Drug: Paclitaxel; Drug: Nab paclitaxel; Drug: Pemetrexed |
| Cohort 3E | Experimental | Lifileucel 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. Receives: Biological: Lifileucel; Biological: LN-145; Drug: Pembrolizumab; Drug: Cisplatin; Drug: Carboplatin; Drug: Paclitaxel; Drug: Nab paclitaxel; Drug: Pemetrexed |
| Cohort 1D | Experimental | Lifileucel (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. Receives: Biological: Lifileucel; Drug: Nivolumab-relatlimab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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)
Measured: 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
Measured: Up to 60 months
Secondary outcomes (5)
Complete Response Rate
To evaluate efficacy using Complete Response (CR) rate per RECIST 1.1, as assessed by the Investigator
Measured: Up to 60 months
Duration of Response
To evaluate efficacy using Duration of Response (DOR) per RECIST 1.1, as assessed by the Investigator
Measured: Up to 60 months
Disease Control Rate
To evaluate efficacy using Disease Control Rate (DCR) per RECIST 1.1, as assessed by the Investigator
Measured: Up to 60 months
Progression-Free Survival
To evaluate efficacy using Progression-Free Survival (PFS) per RECIST 1.1, as assessed by the Investigator
Measured: Up to 60 months
Overall Survival
To evaluate efficacy using Overall Survival (OS)
Measured: Up to 60 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Aug 2018
- Study start7 May 2019
- Primary completion20 Feb 2026
- Study completion20 Feb 2026
Why it 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.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Metastatic MelanomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 225 participants (actual)
Sponsor and investigators
- Lead sponsor
- Iovance Biotherapeutics, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Iovance Biotherapeutics Medical Monitor, Study director, Iovance Biotherapeutics
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03645928
- Sponsor's protocol ID
- IOV-COM-202
- Other IDs
- 2018-001608-12, 2024-510779-39-00, 2018
- Status last verified
- May 2026
- First submitted
- 22 Aug 2018
- Last updated
- 15 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
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.
PubMed 35880942
Study at a glance
From the registry record, last updated by the sponsor on 15 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2, Multicenter Study of Autologous Tumor Infiltrating Lymphocytes (LN 144/LN-145/LN-145-S1) in Patients With Solid Tumors
- ClinicalTrials.gov ID
- NCT03645928
- Acronym / sponsor ID
- IOV-COM-202
- Conditions
- Metastatic Melanoma, Squamous Cell Carcinoma of the Head and Neck, Non-small Cell Lung Cancer
- Keywords
- LN-144, LN-145, Cell Therapy, Autologous Adoptive Cell Transfer, Autologous Adoptive Cell Therapy, Cellular Immuno-therapy, Tumor Infiltrating Lymphocytes, TIL
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason 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.
- Enrolment
- 225 participants (actual)
- Lead sponsor
- Iovance Biotherapeutics, Inc.Industry (pharma, biotech, devices)
- Study start
- 7 May 2019 (actual)
- Primary completion
- 20 Feb 2026 (actual)
- Study completion
- 20 Feb 2026 (actual)
- First posted
- 24 Aug 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
TIL [LN-144/LN-145 (lifileucel) and 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 lymphodepletion (NMA-LD) regimen, followed by autologous TIL infusion , then aldesleukin administration. Patients in Cohorts 1A, 1D, 2A, 3A, 3C, 3D, and 3E will receive TIL plus immune checkpoint inhibitors. Patients in Cohorts 1B, 1C, and 3B will receive autologous TIL as a single therapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 10
| Arm | Type | Receives |
|---|---|---|
| Cohort 1A | Experimental | Biological: Lifileucel, Drug: PembrolizumabLifileucel (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 | Experimental | Biological: LN-145-S1LN-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 | Experimental | Biological: LifileucelLifileucel (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 | Experimental | Biological: Lifileucel, Biological: LN-145, Drug: PembrolizumabLifileucel (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 | Experimental | Biological: Lifileucel, Biological: LN-145, Drug: PembrolizumabLifileucel (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 | Experimental | Biological: Lifileucel, Biological: LN-145Lifileucel (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 | Experimental | Biological: Lifileucel, Biological: LN-145, Drug: Ipilimumab, Drug: NivolumabLifileucel (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 | Experimental | Biological: Lifileucel, Biological: LN-145, Drug: Pembrolizumab, Drug: Cisplatin, Drug: Carboplatin, Drug: Paclitaxel, Drug: Nab paclitaxel, Drug: PemetrexedLifileucel 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 | Experimental | Biological: Lifileucel, Biological: LN-145, Drug: Pembrolizumab, Drug: Cisplatin, Drug: Carboplatin, Drug: Paclitaxel, Drug: Nab paclitaxel, Drug: PemetrexedLifileucel 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 | Experimental | Biological: Lifileucel, Drug: Nivolumab-relatlimabLifileucel (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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (15 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LifileucelAlso: LN-144, TIL, autologous tumor-infiltrating lymphocytesA 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. | Biological | Cohort 1A, Cohort 1C, Cohort 1D, Cohort 2A, Cohort 3A, Cohort 3B, Cohort 3C, Cohort 3D, Cohort 3E |
| LN-145Also: TIL, autologous tumor infiltrating lymphocytesA 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. | Biological | Cohort 2A, Cohort 3A, Cohort 3B, Cohort 3C, Cohort 3D, Cohort 3E |
| PembrolizumabAlso: KeytrudaHumanized antibody. Pembrolizumab will be administered after tumor resection and will continue every 3 weeks or every 6 weeks for up to 2 years. | Drug | Cohort 1A, Cohort 2A, Cohort 3A, Cohort 3D, Cohort 3E |
| LN-145-S1Also: TIL, autologous tumor-infiltrating lymphocytes, PD-1-selected TILA 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. | Biological | Cohort 1B |
| IpilimumabAlso: YervoyMonoclonal antibody Ipilimumab will be administered as a single dose prior to tumor resection. | Drug | Cohort 3C |
| NivolumabAlso: OpdivoMonoclonal 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. | Drug | Cohort 3C |
| Nivolumab-relatlimabAlso: OpdualagMonoclonal 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. | Drug | Cohort 1D |
| CisplatinCisplatin administered intravenously at the protocol-defined dose every 3 weeks for up to 4 cycles. | Drug | Cohort 3D, Cohort 3E |
| CarboplatinCarboplatin administered intravenously at the protocol-defined dose every 3 weeks for up to 4 cycles. | Drug | Cohort 3D, Cohort 3E |
| PaclitaxelPaclitaxel administered intravenously at the protocol-defined dose every 3 weeks for up to 4 cycles. | Drug | Cohort 3D, Cohort 3E |
| Nab paclitaxelNab-Paclitaxel administered intravenously at the protocol-defined dose every 3 weeks for up to 4 cycles. | Drug | Cohort 3D, Cohort 3E |
| PemetrexedPemetrexed administered intravenously at the protocol-defined dose every 3 weeks for up to 4 cycles. Optional continuation maintenance every 3 weeks, if applicable. | Drug | Cohort 3D, Cohort 3E |
Primary outcome
Objective Response Rate
Time frame: Up to 60 months
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
Safety Profile Measured by Grade ≥3 TEAEs
Time frame: Up to 60 months
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)
Percentage of patients for whom lifileucel is successfully manufactured and meets release specification
Time frame: Up to 60 months
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
5 secondary outcomes
Complete Response Rate
Time frame: Up to 60 months
Duration of Response
Time frame: Up to 60 months
Disease Control Rate
Time frame: Up to 60 months
Progression-Free Survival
Time frame: Up to 60 months
Overall Survival
Time frame: Up to 60 months
Results and safety
The study was stopped early (reason given: 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.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 May 2026.
- Derived from this study: PubMed 35880942Hensel 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Iovance Biotherapeutics Medical Monitor study director
Iovance Biotherapeutics
34 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Lifileucel, LN-145 and Pembrolizumab in people with Metastatic Melanoma and Squamous Cell Carcinoma of the Head and Neck, run by Iovance Biotherapeutics, Inc. at 34 sites in 7 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 15 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 34 sites in United States, Spain, Greece, Switzerland, United Kingdom and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: 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.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective Response Rate (time frame: Up to 60 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03645928, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 May 2026.